1. A Journey From Pills to Cells | Dr Pradeep Mahajan | 1
GIST OF PROFILE
CHAIMAN & MANAGING DIRECTOR
STEMRX BIOSCIENCE SOLUTIONS PVT. LTD.
• Guiding a well qualified team of scientists and
researchers working 24x7 for developing cellular
medicine protocols for various disorders.
• Looking forward to taking this therapy to the
common man
DIRECTOR
DR. P. V. MAHAJAN HOSPITAL & INDUSTRIAL TRAUMA CARE CENTRE
• Providing services for trauma care / industrial
injuries
• Occupational Health Hazard management services.
DIRECTOR
SIDDHARTH MARINE HEALTH SERVICES PVT. LTD.
• Consultation and emergency management
DIRECTOR
MEDI-CHECK HEALTH SERVICES PVT. LTD.
• Corporate health check-ups at affordable rates
• Occupational health services
HON. UROSURGEON AND CONSULTING SURGEON
• Continues to perform surgical procedures as
honorary charitable service at MATHADI TRUST
HOSPITAL
• Associate Professor for department of Surgery at
Cooper Hospital of MCGM, Mumbai
VISION & MISSION
• To make all incurable disorders / non-treatable
diseases treatable and improve the quality of life of
every living being.
PHILOSOPHY OF PROFESSION
“Be focused and work towards excelling
in your goal. Compete with yourself and
not others.”
“Never say no to a patient.’’
MOST PROUD OF
• My decision to change from being a general surgeon
and academician to a regenerative medicine
researcher has proved to be a game changer
which enabled me to explore the unexplored in a
passionate and successful manner.
CHARACTER STRENGTHS
• Commitment and dedication
• Perseverance
• Convincing communication
• Simplicity
LANGUAGE FLUENCY
• English
• Hindi
• Marathi
HIGHER EDUCATION
• M.S.
• AFIH
• Diploma in Urology from University of Vienna,
Austria
A DAY IN MY LIFE
Patients for
counselling
and
procedures
Self-development
Dr. PRADEEP V. MAHAJAN
UROSURGEON AND REGENERATIVE MEDICINE RESEARCHER
@ drpvmahajan@gmail.com www.stemrx.in Andheri, Mumbai, India
Colleagues
and
supporting
staff for
smooth
working
and their
professional
development
Family
2. 2 | Dr Pradeep Mahajan | A Journey From Pills to Cells
INDEX
CITATION 04
PROFILE
General Profile
Academics 06
Academic achievements 06
Teaching experience 06
Training programmes 07
Research experience
Research papers and articles published 07
Articles/ abstracts 07
Current engagements 08
Awards And Accolades
Awards 09
Landmark Achievements 10
Social Activities 10
Associate Memberships 11
Patents 11
Keynote Address
International conferences 11
National conferences 11
MEDIA COVERAGE
Print Media 12
Articles in newspaper
Electronic Media
‘Hitguj’ - Zee 24 Taas 12
Miscellaneous 14
SUCCESS STORIES THOSE CREATED HISTORY 64
CASE STUDY
Neurogenic bladder 68
CERTIFICATES
The Ohio State University 71
9th
annual translational to clinical regenerative medicine 71
wound care conference
Indian stem cell study group meeting 72
Ioracon - 2015 72
Participation as delegate/faculty in ‘An update in various medical 73
managements’
3. A Journey From Pills to Cells | Dr Pradeep Mahajan | 3
Participation in CME by Indian Medical Association, Navi Mumbai 73
Participation as delegate in ‘Practice management of doctors’. 74
‘MASCON-2012 : Basics and Beyond’ 74
Participation in CME by Indian Medical Association, Navi Mumbai 75
Participation in CME by Indian Medical Association, Navi Mumbai 76
Participation as a faculty in CME by Indian Medical Association,
Navi Mumbai 76
AMCON 2011- 12 77
Sri Raghavendra biotechnologies pvt. ltd. 77
Rotary Club of Bombay, Airoli 77
Antiaging comprehensive certification 78
Certificate of registration (Directorate General Factory Advice
Service and Labour Institutes) 78
Indian achiever’s award for health excellence 79
Participation in basic laparoscopic surgery training programme 80
EMCON - 2004 80
Urological society of India 81
Special executive magistrates’ society 81
Fellowship in urology, Vienna 82
American medical society, Vienna 82
Internship completion certificate (Marathwada University) 83
MBBS (Marathwada University) 83
Maharashtra Medical Council 83
Registration certificate for additional medical qualification 84
2016 leaders awards 84
National award for excellence in healthcare 84
PUBLICATIONS 85
4. 4 | Dr Pradeep Mahajan | A Journey From Pills to Cells
Citation
Dr. Pradeep Mahajan is a leading stem cell researcher and stem
cell transplant surgeon rated as one of the best among the top
few renowned clinical stem cell researchers. He has received
‘2016 Leadership award’ for his company ‘StemRx Bioscience
Solutions Pvt. Ltd.’ for the fastest growing healthcare brand for
stem cell treatment in Maharashtra and also ‘National Awards
for Excellence in Healthcare’ for the Best Clinical Research
Company in 2016. A pioneer in the field of stem cell research, he
has been amongst the first few to recognize enormous potential
of stem cells and to treat the patients waiting for cure with this
amazing technology. He has received a Gold Medal from Special Executive Magistrates’ Society
of Mumbai for services in trauma care on highway. He has also received ‘Indian Achiever Award
for Healthcare Excellence’ in 2006.
Dr. P. V. Mahajan is a graduate of SRTR Medical College from Marathwada University with laurels
of two gold medals in MS (Master in Surgery) from Marathwada University. He has also received
‘Late Shri Narayanrao Chitgopekar Prize’ for the best performance in MS (General Surgery)
examinationheldinNovember1987atMarathwadaUniversity.HeholdsDiplomainUrologyfrom
Vienna University and is a member of American Medical Society of Vienna. He has undergone
several training courses in stem cells and regenerative medicine and is known for his profound
knowledge in cellular medicine. Amongst the various training programmes, training at Ohio
State University, US is noteworthy. He has also obtained an Associate Fellowship of Industrial
Health from the Central Government’s Labour Institute, Laparoscopic Surgical training and a
certificate course from KEM Hospital.
Dr. Pradeep Mahajan has got numerous national and international recognitions for his research
and innovative work in the field of clinical research in regenerative medicine and cell based
therapy. This got him the most dignified appointment of honourary professor for regenerative
medicine and cell based therapies in Cooper Hospital, Mumbai. He was also honoured by the
Government of India and Government of Maharashtra by appointing as consultant and panel
doctor with the director general of shipping and labour department. Dr. Mahajan is a member
of board of studies in ITM University, Raipur for PhD courses in stem cells and regenerative
medicine. For his outstanding contribution in the field of clinical research in regenerative
medicine and cell based therapy, Dr. Mahajan has been felicitated by ‘The Centre of Regenerative
medicine and Cell Based Therapies’, Ohio State University, US, in 2015 which also invited him to
participate in the exclusive training programme in organ development and tissue engineering.
He has worked as an associate professor of surgery at Terna Medical College, Navi Mumbai.
Dr.PradeepMahajanisFounderandChairmanaswellasManagingDirectorofStemRxBioscience
Solutions Pvt. Ltd. Under his dynamic and able guidance, several scientists and researchers
are working 24x7, developing cellular medicine protocols in various treatment modalities of
diseases and disorders of orthopaedic conditions, metabolic conditions, neurodegenerative
5. A Journey From Pills to Cells | Dr Pradeep Mahajan | 5
disorders and many more. Dr. Mahajan has filed a patent for the treatment procedure of AVN
(Avascular Necrosis of Femoral Head) through regenerative medicine (Application No: 1369/
MUM/2014) and also applied for international patent ‘Osteoinductive Formulation and
Preparation Thereof’ (Application No: PCT/IN2015/000173). Other patents to his credit are :
“How to treat Ankylosing Spondylitis?” and “How to develop IT-MSC technology (Ischemic
tolerance MSC Treatment)?”. He has several research publications in national and international
journals in regenerative medicine.
Dr. Pradeep Mahajan has been credited national and international publications in clinical
research in regenerative medicine and cell based therapies. Dr. Pradeep Mahajan has written
and published a book on ‘Antidotes and Management of Chemical Poisoning’.
He introduced new technology with minimal manipulation of bone marrow and adipose tissue
stem cells. With this technology he treated more than 2000 cases of various conditions which
could not be treated by conventional method. He quotes, “You carry your own repairing kits
in your body”. He brought this technology to common people at the lowest cost. Dr. Mahajan
was invited to present his work on minimal manipulation of bone marrow and adipose tissue
stem cells for regenerative therapy, to Ohio State University, US. There are many cancer patients
treated by cell based therapy under ‘Family Welfare Charitable Trust’ founded by Dr. P. V.
Mahajan.
Dr. Mahajan has academic collaboration with ITM University (Raipur) and MUHS (Nashik) as well
as Ohio State University (USA) for different academic courses with his organization- ‘StemRx
Bioscience Solutions Pvt. Ltd.’ He is also aggressive in research projects wherein they are the
collaborative partners with Sanostem (USA), Stemedica (USA), Autostem Pvt Ltd (Chennai) and
Ohio State University (USA) for different clinical trials and research programmes. With the vision
of serving humanity better in the healthcare industry, his company StemRx Bioscience Solutions
Pvt. Ltd., has come up with multifacility research centre with advanced cell culture and research
laboratory established with world class facilities at Andheri, Mumbai. This research facility is
working under his guidance on molecular and cellular medicine.
Dr. Pradeep Mahajan has treated world’s youngest baby girl of age 14 months for cerebral palsy
with cell based therapy. He has also to his credit, achievement of treating world’s first case and first
person of ENS (Empty Nose Syndrome) using regenerative medicine and cell based therapy.
Through various social and health informative activities, Dr. Mahajan is very active in arranging
CMEs in regenerative medicine. He is regularly visited as a speaker of ‘Hitguj’ – a Zee 24 Taas
TV programme through which he successfully shares the knowledge of regenerative medicine
therapies available for different diseases for public and common man education. Dr. P. V. Mahajan
regularly publishes his articles on stem cell clinical research and regenerative medicine in print
media to create awareness and IEC among common people.
Dr. Pradeep Mahajan has performed more than 3500 charitable surgeries in the last 20 years
at Mathadi Charitable Hospital, Navi Mumbai. He took initiative in organising more than 100
health camps in association with the Rotary Club and also served as Charter President of Rotary
Club, Airoli. He has conducted many health camps for social organizations and police department,
vaccination camps and first aid training programmes.
6. 6 | Dr Pradeep Mahajan | A Journey From Pills to Cells
Profile
GENERAL PROFILE
ACADEMICS :
Qualification Board/ University/ Institute Year
SSC Nanded Board March 1977
HSC Nanded Board March 1979
MBBS Marathwada University February 1985
MS Marathwada University February 1988
DU (Diploma in Urology) University of Vienna, Austria September 1991
AFIH Labour Institute of Central
Govt., Sion
2005
Laparoscopic surgical
training and certificate
course
KEM hospital, Mumbai 2005
ACADEMIC ACHIEVEMENTS :
• Two times GOLD MEDALIST in MS (Surgery) from Marathwada University.
• Recipient of Late Shri. Narayanrao Chitgopekar Award for best performing candidate in 1987
in MS (General Surgery) exam.
TEACHING EXPERIENCE :
• Hon. associate prof. of regenerative medicine at H.B.T.M.C and Dr. R. N. Cooper General
Hospital, Mumbai.
• Hon. associate prof. of regenerative medicine at Maharashtra University of Health Sciences
(MUHS), Nashik.
• Visiting faculty at dept. of regenerative medicine and stem cells, Ohio State University, US.
• Associate prof. of surgery at Terna Medical Collage, Nerul and minimal invasive surgery.
• Teaching experience at urology dept., University of Vienna, Austria, in endourology, ESWL
and minimum invasive surgery.
• Faculty member for advance diploma in industrial safety course for occupational diseases
and Continuous Education Programme (CEP) of Directorate of Industrial Safety and Health
(DISH) and Thane Belapur Industries Association (TBIA).
• Examiner for MBBS at MUHS, Nashik.
• Professor for CPS course.
7. A Journey From Pills to Cells | Dr Pradeep Mahajan | 7
TRAINING PROGRAMMES :
• Tissue culture, Ohio State University, USA for stem cell therapy.
• Laparoscopic surgery training for outside occupation health hazard and electronic management.
• Training in antiaging comprehensive module.
RESEARCH EXPERIENCE :
• Credited for national and international publications in clinical research in regenerative medicine
and cell based therapies.
• Writing and publishing of a book on ‘Antidotes and Management of Chemical Poisoning’.
• Through an unexplored subject ‘Nature Heals Through Nature’ he is providing an alternative to
traditional surgery with multiple drugs using treatment protocols of regenerative medicine cellular
biology (stem cells).
• Introduced new technology with minimal manipulation of bone marrow and adipose tissue stem
cells. With this technology he has treated more than 2000 cases of various conditions, which could
not be treated by conventional method.
• Dr. Mahajan was invited to Ohio State University to present his work on minimal manipulation of
bone marrow and adipose tissue stem cells for regenerative therapy.
Research Papers And Articles Published
• Pradeep V. Mahajan, Anurag P. Bandre, Nitin S. Desai :
‘Study of cell therapy assisted regeneration of cartilage in avascular bone necrosis’ D. Y. Patil Journal
of Health Sciences, 2014, 2(1): 41-45
• Pradeep V. Mahajan, Anurag P. Bandre, Nitin S. Desai :
‘Changing Paradigms in Healthcare Medicine’ Indian Journal Of Stem Cell therapy, 2014, 1, 50-53
• Pradeep V. Mahajan, Prabhu Mishra :
‘A novel cell based treatment for Avascular Necrosis of Femoral Head’ (A case report) Journal of
Indian Orthopaedic Rheumatology Association, 2015, 1 (1), 17-21
• Pradeep V. Mahajan :
‘Role of Autologous Stem Cell Therapy in Relapsing Remitting Multiple Sclerosis’ (A case Report)
Articles/ Abstracts
• Evaluation of suture materials in (surgical) wounds.
• Abstract in Health Science Innovation on ‘Revamping of Regenerative Medicine’, Jan 2015
8. 8 | Dr Pradeep Mahajan | A Journey From Pills to Cells
• Abstract in Stem Cell Society of India and Indian Federation of Neuro-Rehabilitation on ‘Stem cell
niche and Therapeutic Application of Stem Cells’, March 2014
CURRENT ENGAGEMENTS :
• Chairman and Managing Director, StemRx Bioscience Solutions Pvt. Ltd.
• Director, Dr. Mahajan Hospital and Industrial Trauma Centre, Rabale, Navi Mumbai.
• Director, Sidhharth Marine Health Services Pvt. Ltd, Mumbai.
• Director, MEDI-CHECK Health Services Pvt. Ltd ., Rabale, Navi Mumbai.
• Hon. urosurgeon and consulting surgeon for Mathadi Trust Hospital since 1993.
• Member of board of studies in ITM University Raipur for PhD courses in stem cells and regenerative
medicine.
• Academic collaboration with ITM University (Raipur), MUHS (Nashik) and Ohio State University
(USA) for different academic courses in the area of stem cell and regenerative medicine.
• Consultant and panel doctor, shipping and labour department.
• Consulting occupation physician to industries in Thane district.
AWARDS AND ACCOLADES
• Dr. Mahajan has won several accolades for his abstracts on health science innovation ‘Revamping of
Regenerative medicine’ in January 2015 and for another abstract ‘Stem Cell Niche and Therapeutic
Application of Stem Cells’, published in March 2014 in Stem Cell Society of India and Indian
Federation of Neuro Rehabilitation.
• Dr. Mahajan has been a part of several national and international conferences. He has presented
severalpapersofinternationalimportance,suchasStemCellsforOrthopedicCondition,Therapeutic
Application of Cancer Stem Cells and Cancer Stem Cells, Revamping of Regenerative medicine,
Stem Cell Niche and Stem Cells Therapeutic Application and Therapeutic Application of Stem Cells.
• Dr. Mahajan has got numerous national and international recognitions for his research and
innovative work in the field of clinical research in regenerative medicine and cell based therapy. This
got him the most dignified appointment of honourary professor for regenerative medicine and cell
based therapies in Cooper Hospital, Mumbai.
• Dr. Mahajan has also gained an international reputation for his research on cell therapy, assisted
regeneration of cartilage in avascular bone necrosis. His research paper on ‘Changing Paradigms in
Healthcare Medicine’ was published in the most reputed Indian Journal of Stem Cell Therapy.
• He was also honoured by the Government of India and Government of Maharashtra by appointing as
a consultant and panel doctor with the director general of shipping and labour department.
9. A Journey From Pills to Cells | Dr Pradeep Mahajan | 9
Awards
• Mrs. Mayadevi S. Darake Prize
• Gold Medal from Special Executive Magistrates’ Society of Mumbai for
Services in Trauma care on highway.
• Indian Achievers Award for Health Excellence, Delhi, for outstanding
achievements in healthcare sector in India at 14th
national seminar on
corporate achievements and social responsibilities.
• 2016 Leaders Award for ‘Fastest Growing Healthcare Brand for Stem Cell
Treatment in Maharashtra’.
• Award at ITC Grand Central, Parel on July 22, 2016.
10. 10 | Dr Pradeep Mahajan | A Journey From Pills to Cells
LANDMARK ACHIEVEMENTS
• Carried out more than 3500 operations.
• Nearly 2000 operation procedures carried out at Mathadi Hospital, Navi Mumbai.
• Successfully treated world’s youngest case of Cerebral Palsy in which the age of the patient was
14 months.
• Treated world’s first case of ENS (Empty Nose Syndrome).
• Carried out more than 500 CME programmes to educate medical fraternity and patients both
alike.
• Dr. Mahajan’s hospital was the first of its kind Industrial Trauma Care Hospital to be setup in
Navi Mumbai.
SOCIAL ACTIVITIES
• Through various social and health informative activities, Dr. Pradeep Mahajan is very active in
arranging CMEs in regenerative medicine.
• He is also an active member of the Local Cities Committee, headed by the Commissioner of
Navi Mumbai. His campaign on HIV awareness for the industrial workers has won him several
accolades.
• Dr. Pradeep Mahajan has performed more than 3500 charitable surgeries in the last 20 years
at Mathadi Charitable Hospital, Navi Mumbai. He took initiative in organising more than 100
health camps in association with Rotary Club and also served as a Charter President of Rotary
Club, Airoli and also conducted many health camps for social organization, police department,
vaccination camps, first aid training programmes.
• As a practicing Urological surgeon with Mathadi Trust Hospital in Navi Mumbai for the past 22
years, he has worked for the welfare of the people.
• He is currently the Charter President of Rotary Club of Airoli and an active member of
Envirosafe Foundation of Safety, Health and Environment (SHE).
• He is also an active member of the Local Cities Committee, headed by the Commissioner of
Navi Mumbai.
• During his tenure as a medical practitioner, he had organized many health camps for social
organizations, police departments and had been instrumental in organizing several vaccination
camps to do away with the dreaded diseases.
• In his literary pursuit, Dr. Mahajan has authored a medical book, named as ‘Antidotes and
Management of Chemical Poisoning’. His case report titled ‘Neurogenic bladder repair using
autologus mesenchymal stem cells’ has been considered for publishing.
11. A Journey From Pills to Cells | Dr Pradeep Mahajan | 11
ASSOCIATE MEMBERSHIPS
• Treasurer of SCSI.
• Vice president of Antiaging Foundation, Delhi.
• Vice president of Surgeons’ Certifying Association of Maharashtra.
• Member of International Stem Cell Society, Singapore.
• Ex. member of ISCSG.
• Member of IORA.
PATENTS
• National patent for treating Ankylosing Spondylitis and how to develop IT-MSC (Ischemic
Tolerance MSC Treatment)
• Applied for – National patent for treatment procedures of AVN (AVascular Necrosis of
femoral head)
• Applied for – International patent for osteoinductive formulation on preparation thereof
KEYNOTE ADDRESS
INTERNATIONAL CONFERENCE
• Mesenchymal Stem Cells (MSC): Changing Paradigm, The New Medicine VII and 1st
Stem Cell
Society of India (SCSI) (June 2016), Mumbai.
• ‘Stem Cells for Orthopedic Conditions (AVN)’ held by 1st
Annual Conference of All India
Orthopedic Surgeons Council at Madurai (September 2015).
• ‘Therapeutic application of Cancer Stem Cells’ held by Ohio State University, USA (August
2015).
• ‘Cancer Stem Cells’ held by 1st
Annual Conference of All India Conference on Recent Advances
in Cancer Management, at Symbiosis, Pune (June 2015).
• ‘Revamping of Regenerative Medicine’ at Health Science Innovation Conference, Taj Palace,
Mumbai held by Ohio State University, USA and All India Institute of Medical Sciences (January
2015).
• ‘Stem Cell Niche and Stem Cells Therapeutic Application’ at (International association of
Neororestoratology) IANR VII and 1st
Stem Cell Society of India (SCSI) with 11th
GCNN and 2nd
(Indian Federation of Neuro-Rehabilitation) IFNR Conference, Mumbai (March 2014).
NATIONAL CONFERENCE
• ‘Therapeutic application of stem cells’ held by Stem Cell Society of India at India Heritage
Centre, New Delhi (May 2015).
• Smart Living Workshop on ‘Anti Aging’, organized by Saket hospital, New Delhi, (August 2013)
MMC recognized CME on ‘Stem cell technology and its applications in medicine’ organized by
D. Y. Patil Hospital and Research Center, Nerul, Navi Mumbai. (December 2013).
12. 12 | Dr Pradeep Mahajan | A Journey From Pills to Cells
Media coverage
PRINT MEDIA
• The work done by Dr. Mahajan has received wide coverage in variety of national and
international media including India Today, Asian Age, Telegraph, regional publications,
NDTV(News Channel), Dublin News, Ireland and Brazil Sun.
• Article on ‘Stem Cells cure Multiple Sclerosis’ in Dublin News, Ireland on 18th February 2016.
• Article on stem cells in India Today on February 2014.
• Article on stem cell therapy in Maharashtra Times, 20th April 2016.
ELECTRONIC MEDIA
• Dr. Mahajan is regularly invited by a leading Marathi Channel Zee 24 Taas to share his views
on the topic - ‘stem cell therapy and its application’. It addresses to
1. Stem cells and their applications.
2. Applications of stem cells in the treatment of avascular necrosis(AVN).
3. Applications of stem cells in the treatment of diabetes.
4. Stem cells: Major remedy on uncurable diseases.
5. Role of stem cells in the treatment of bone diseases.
• A documentary on NDTV titled ‘Future of Medicine’ featuring the research has been telecast.
14. 14 | Dr Pradeep Mahajan | A Journey From Pills to Cells
IOSR Journal of Dental and Medical Sciences (IOSR-JDMS)
e-ISSN: 2279-0853, p-ISSN: 2279-0861. Volume 15, Issue 4 Ver. 1 (Apr. 2016), PP 127-130
www.iosrjournals.org
Role of Autologous Stem Cell Therapy in Relapsing Remitting
Multiple Sclerosis: A Case Report
Dr. P. V. Mahajan1
, Dr. Swetha Subramanian2
, Mr. Anurag Bandre3
, Dr. Anand Kumar4
1
CMD, StemRxBioscience Solutions Pvt. Ltd., Rabale, Navi Mumbai
2
Clinical Assistant, StemRxBioscience Solutions Pvt. Ltd., Rabale, Navi Mumbai
3
Manager (Lab Operations), StemRxBioscience Solutions Pvt. Ltd., Rabale, Navi Mumbai
4
Director (Lab Operations), StemRxBioscience Solutions Pvt. Ltd., Rabale, Navi Mumbai
ABSTRACT:
Multiple sclerosis is a progressive disease characterized by accumulating disability. Although advances in
conventional treatment have been made to reduce the relapse rate, these modalities do little in terms of repair to
the damaged CNS. Cellular therapy represents a promising approach in management of neurological conditions
associated with morbid outcomes. Mesenchymal stem cells (MSC) foster repair of the CNS through tissue integration
and differentiation into neural cells. Additionally, through mechanisms of neuroprotection and immunomodulation,
MSCs may be effective in the treatment of multiple sclerosis. This report presents a case of relapsing remitting multiple
sclerosis treated with autologous stem cells.
Keywords: Multiple sclerosis, Mesenchymal stem cells, Platelet rich plasma
INTRODUCTION:
Multiple sclerosis (MS) is considered as an immune-mediated disease associated with immune activity directed
against central nervous system antigens that frequently leads to severe physical and cognitive impairment. Structures
within the nervous system damaged in MS include myelin, oligodendrocytes and underlying nerve fibers.
MS has been reported to affect more than 2 million people worldwide and is considered the most common non-
traumaticcauseofdisabilityinyoung(<50years)Europeanadults[1].MShastwodistinctclinicalphasescorresponding
to inter-related pathological processes: focal inflammation that drives activity during the relapse-remitting stage and
neurodegeneration that underlies progressive disease characterized by accumulating fixed disability [2].
Histologically, active lesions are characterized by presence of macrophages containing fragments of myelin.
Perivascular inflammatory infiltrate mostly composed of T-lymphocytes, reactive astrocytosis and microglial cells
are also seen. Oligodendrocytes are usually preserved or slightly reduced in newly demyelinating lesions. Chronic
inactive plaques are associated with dense fibrillary gliosis, loss of oligodendrocytes, few microglial cells and marked
reduction of axonal density [3].
MSCs may be effective in treatment of multiple sclerosis through mechanisms of neuroprotection,
immunomodulation and neuroregeneration [4]. These properties may aid in reducing damage in the central nervous
system of MS patients, which results from imbalance between the deleterious immune response and failure of the
remyelinating mechanisms.
The following report describes autologous stem cell therapy along with platelet rich plasma administration in a
patient with known history of multiple sclerosis unresponsive to standard therapy.
CASE REPORT:
A 19 year old male patient reported to StemRx Bioscience Solutions Pvt. Ltd. with the complaints of recurring gait
disturbances and inability to perform daily activities effectively.
Medical history revealed that he first experienced loss of consciousness while playing on a ground before 4 years.
He was unable to lift his leg thereafter and consulted a local physician for the same for which he was given medication
for a brief period. Six months later, the patient was admitted to a hospital with the complaint of heaviness in his
right leg and gait disturbance. Blood and radiological investigations were done and MRI revealed that the patient
suffered from Multiple Sclerosis. He was under steroid medication for 3 months and the symptoms were brought
under control. Over the course of the following year, the patient repeatedly had the previously mentioned complaints
in addition to uncontrolled movements of the neck, inability to write, talk clearly and urine incontinence. Steroid
therapy was advised which temporarily relieved the symptoms, however, the patient gradually stopped responding
to the medications (in about 2 years after the therapy was initiated). Thereafter, immuno-modulatory therapy with
15. A Journey From Pills to Cells | Dr Pradeep Mahajan | 15
beta-interferon was given for 6 months followed by alternative medicine modalities for 1-1.5 years, none providing
any improvement of symptoms. In July 2014, the patient was bedridden following an episode of fever and general
weakness.
On the first visit of the patient, complete radiological and hematological investigations were done. Hematological
assessment did not reveal any abnormalities with the exception of positive C-reactive protein level. The positive level
indicates that CNS inflammatory response in MS is dependent on the peripheral immune compartment [5]. Fig. 1a &
1b show the MRI images taken before and after initiation of conventional treatment. Clinical assessment criteria have
been presented in Table 1.
A final diagnosis of Recurrent Relapsing Multiple Sclerosis was made. The relapsing-remitting subtype is
characterized by unpredictable relapses followed by period of months to years of relative remission with no new
signs of disease activity.
STEM CELL THERAPY:
Three sessions of stem cell therapy with an interval of 15 days between every two consecutive sessions was
planned for the patient during his initial stay at the hospital. Follow up was done after 3 months during which two
more sessions of cellular therapy were advised. Approximately 100 ml. of bone marrow from the right iliac crest, 70-
80 ml. of adipose tissue from right gluteal region was aspirated under local anesthesia. 50 ml. of peripheral blood was
obtained from right cubital vein.
Stemcelltransplantationwasdonebyintrathecal,intravenousandintranasalroutes.Inaddition,intravenousdose
of PRP, which is a platelet concentrate and a reservoir of growth factors was administered. Physiotherapy exercises,
neuromuscular stimulation, yoga, nutraceuticals and a balanced diet specific for the patient’s condition were advised.
RESULTS:
Clinically, positive effect of treatment was defined as A decrease in EDSS of 1.0 point or greater compared with
baseline. The response to cellular therapy provided was seen during the first follow up period. The patient regained
some of his abilities to perform routine activities with assistance. Graph 1 shows the improvement in functional
system scores following cellular therapy. The improvement noticed in individual functional system was gradual, but
that was considered a positive effect on our part as the patient was bedridden when he first reported to the hospital.
Fig. 1c shows the resolution of lesions in periventricular region in the MRI taken one year after the cellular
therapy. However, three tiny foci of restricted diffusion involving bilateral frontal subcortical white matter region and
left perirolandic subcortical fronto-parietal white matter regions were observed. Nonetheless, this is considered an
improvement in comparison to the previous extent of lesions, and periodic monitoring will be done to assess any
further changes and plan treatment if needed at a later stage.
It was observed that the patient could walk on his own with occasional support. Significant improvement in gait
was noticed. He is now able to perform daily activities by himself which was not possible before treatment.
DISCUSSION
Conventional therapies for multiple sclerosis using immunosuppressants, monoclonal antibodies etc. effectively
reduce inflammation; but do little in terms of repair to the damaged central nervous system [6]. Treatment with
beta-interferons was considered as a major advancement in the treatment of this discase; however, their effect is still
limited [7].
The hypothesis of the use of autologous stem cell therapy is based on the theory that environmental factors play
an important role in the pathogenesis of MS and that the therapy could be used to reset the autoimmune cell line
thereby restoring self-tolerance [8]. BM-MSC can promote neuroprotection by inhibiting gliosis, scar formation and
apoptosis, and by stimulating local progenitor cells. It is also possible that these cells may differentiate into neural
cells and contribute to cell replacement.
Stromal vascular fraction (SVF) derived from adipose tissue has been shown to contain mesenchymal stem
cells (MSC), endothelial precursor cells, preadipocytes as well as anti-inflammatory M2 macrophages [9]. MSC
compartment from SVF inhibit innate immune activation by blocking dendritic cell maturation and subsequently
suppress adaptive immunity by generating T regulatory (Treg) cells and blocking cytotoxic activities of CD8 cells.
In this report, we observed an improvement in clinical parameters, the results of which are being maintained.
This is consistent with findings reported by Yamout et al. (2010) who stated that early signs of clinical improvement
following BM-MSC transplant are seen in most patients by 3 months and maintained up to 1 year [10]. Also, Liang et
al. (2009) reported decrease in EDSS of at least 2 points from the baseline of 8.5, in a female patient diagnosed with
primary progressive MS, which was confirmed during 2 months after transplantation of allogeneic mesenchymal
stem cells [11]. These reports along with our findings support the effectiveness of stem cell therapy in multiple
16. 16 | Dr Pradeep Mahajan | A Journey From Pills to Cells
sclerosis. This could be attributed to the potential for migration of mesenchymal stem cells into inflamed CNS tissue
and differentiation into cells expressing neuronal and glial cell markers.
Researchershavestatedthatmyelinrepaircanhappenwithoutinduction,probablyduetoactivationofprogenitor
oligodendrocytes, causing spontaneous remyelination. It has also been found that PDGF plays an important role in
multiplication and growth of these progenitor cells [12]. The administration of PRP in this patient ensured that an
increased number of growth factors such as, PDGF, VEGF, TGF-beta, EGF, FGF, IGF-1 was delivered to the surgical area.
PRP secrete 70% of the stored growth factors within 10 minutes and close to 100% within the first hour. Thereafter
additional amounts of growth factors are synthesized upto 8 days following which the platelets die [13].
Additionally, Brain Derived Neurotrophic Factor (BDNF), which is a member of the neurotrophin family of growth
factors, has been shown to enhance CNS myelinalion during development. BDNF also exerts neuroprotective roles
following demyelination in animal models of MS [14]. Deficient BDNF in T-cells resulted in progressive disability and
enhanced axonal loss; while overexpression of BDNf presented with less severe disease and axonal protection [15].
We administered BDNF drops orally as a supportive modality to enhance myelination.
The goal of diet modifications and neuromuscular rehabilitation in multiple sclerosis is to reduce the oxidative
stress and aid in strength maintenance. For this purpose, a gluten free diet was advised with adequate intake of
protein rich foods, cruciferous vegetables and citrus fruits. Antioxidant supplements were prescribed to further
achieve improved outcomes following the treatment. A gradual improvement in strength and endurance of muscle
groups was noticed 4-5 months after the above protocol was initiated.
CONCLUSION:
The purpose of cellular therapy done for MS is to slow the progression of the disease, minimize symptoms
during exacerbations and to improve physical and mental functions. The injection of MSC was not associated with
any adverse reaction in this patient; and resulted in improvement of clinical parameters along with limiting disease
progression. Nevertheless, further long term follow up is essential to assess the maintenance of results. Also, further
trials are necessary to determine the required cellular dose, number of injections, timing of injections, determining
the best cell subtypes (among stem cell population) to achieve optimum results in patients with multiple sclerosis as
well as other autoimmune conditions.
REFERENCES:
[1] Pugliatti M. Rosati G. Carton H, et al. The epidemiology of multiple sclerosis in Europe, Eur J Neurol, 13, 2006, 700-22.
[2] Compston A, Coles A, Multiple sclerosis, Lancet, 372, 2008, 1502-17.
[3] Roncaroli F, Neuropathology of Multiple Sclerosis, ACNR, 5 (2), 2005.
[4] Uccelli A and Mancardi G, CurrOpinNeuro, 23(3), 2010, 218-25.
[5] Soilu-Hanninen M, Koskinen J.O., Laaksonen M, Hanninen A Lilius E-M, Waris M, High sensitivity measurement of CRP and
disease progression in multiple sclerosis, Neurology, 2005.
[6] Wiendl H and Hohlfeld R, Multiplc sclerosis therapeutics unexpected outcomes clouding undisputed successes, Neurology,
72(11), 20009, 1008-1015.
[7] Vosoughi R and Freedman SM, Case report: Multiple sclerosis and amyotrophic lateral sclerosis, International journal of
MS care, 12(3),2010,142-145.
[8] VanBekkum DW, Stem cell transplantation in experimental models autoimmune diseases, J Clinlmmuno, 20, 2010,10-6.
[9] Neil H Riordan, Thomas E lehim, Wei-Ping Min, Hao Wang, Fabio Solano, Fabian Lara et al, Non expanded adipose stromal
vascular fraction cell theraphy for multiple sclerosis, Journal of Translational Medicine, 7, 2009, 29.
[10] Bassem Yamout a, Roula Hourani, Haytham Saiti, Wissam Barada, Taghrid El-Hajj, Aghiad Al-Kutoubi et al, Bone marrow
mesenchymal stem cell transplantation in patients with multiple sclerosis: A pilot study, J. Neuroimmunol, 2010.
[11] J Liang, H Zhang, B Hua, H Wang, J Wang, Z Han and L Sun, Allogeneic mesenchymal stem cells transplantation in treatment
of multiple sclerosis, Multiple sclerosis, 15, 2009, 644-646.
[12] Woodruff RH., Fruttiger M., Richardson WD, Franklin RJ. Platelet-derived growth factor regulates oligodendrocyte
progenitor numbers in adult CNS and their response following CNS demyelination, Mol Cell Neurosci, 25, 2004, 252-62.
[13] Robert, E. Marx, Platelet-rich plasma (PRP): What is PRP and what is not PRP, Implant dentistry, 10(4), 2001.
[14] Xiao J. Wong A W, Willingham MM, van den BuuseM, Kilpatrick TJ. et al, Brain-Derived Neurotrophic Factor Promotes
Central Nervous System Myelination via a Direct Effect upon Oligodendrocytes, Neurosignals, 18, 2010, 186-202.
[15] LinkerRA,LeeDH.,DemirS.,WieseS,KruseN.etal,Functionalroleorbrain-derivedneurotrophicfactorininneuroprotective
autoimmunity: therapeutic implications in a model of multiple sclerosis, Brain 133, 2010, 2248-2263.
20. 20 | Dr Pradeep Mahajan | A Journey From Pills to Cells
A novel cell based treatment for Avascular Necrosis of femoral head: A
case report
Pradeep V. Mahajan1
*, Prabhu Mishra, Manish Khanna, Anurag Bandre,
Swetha Subramanian, Manu Menon, Nitin Desai2
*
1
Chairman and Managing Director, StemRx Bioscience Solutions Pvt. Ltd.
R-831, T.T.C., Thane Belapur Road, Rabale, Navi Mumbai, Maharashtra, India
2
Amity University, Mumbai, Maharashtra, India
*Corresponding Author:
Email: drpvmahajan@gmaiI.com/Nitindesai@gmail.com
ABSTRACT:
Avascular necrosis (AVN) of femoral head is a progressive disease characterized by a vascular insult to the
blood supply of the femoral head, which can lead to collapse of the femoral head and subsequent degenerative
changes. The femoral head, carpals, humerus are the most commonly affected bones. Regenerative medicine - a
branch of translational research, uses cell based therapies in tissue engineering which deals with the process of
re-engineering or regenerating human cells, tissues or organs at the defective sites to restore or establish normal
function. On the basis of the concept of regenerating cells we present a case that deals with the treatment of
avascular necrosis of femoral head in a 35 year old male patient with cell based therapy.
INTRODUCTION:
The healthcare sector now is not just limited to the concept of organ replacement but has shifted to the
concept of organ regeneration; and cell based therapies have played an important role in this paradigm shift.
Cell based therapies are based on the application of stem cells which are differentiating and immunomodulatory.
Avascularnecrosisisacondition thatoccursduetodisruptionofblood supplytothebonewhichultimatelyleadsto
collapse of the bone. The conventional treatment of AVN may be non-operative and/or operative. Non-operative
treatment modalities include elimination of causative factors, use of anti-osteoporotic agents (bisphosphon-
ates ere), analgesics, non-weight bearing exercises etc. Operative treatment includes core decompression,
joint preservation and replacement (total or partial) procedures. However, the results of the aforementioned
treatment modalities have been unsatisfactory. The extent and the location of the lesion involving the femoral
head determines the prognosis of AVN. Ohzono et al. reported that the lesions involving the lateral one third of
the weight bearing area or diffuse femoral head involvement had more than 90% chance of collapse [1]. Lee et
al.stated that the overall collapse rate of AVN (hips) was 78% within 2 years [2]. In a case study on AVN of the
hip joint, Steinberg et al. reported that 92% of cases progressed to collapse when managed with non-operative
treatment [3].
The use of autologous stem cells has shown promise in halting the progression of AVN of the femoral head
and subsequently preventing young patients from undergoing total hip arthroplasty [4]. Animal experiments have
demonstrated the potential of stem cells to promote neovascularization which effectively increase the blood
perfusion in an anoxic environment and thus inhibit further necrosis of tissues [4,5]. Thus, transplantation of
mesenchymal stem cells may be a minimally invasive strategy for the treatment of femoral head necrosis.
In 2002, Hernigou and Beaujean first described a technique for injecting mesenchymal stem cells
combined with standard core decompression to introduce biologies into an area of necrosis[6]. This study was
done in 116 patients using autologous mesenchymal stem cells and in 5 years clinical follow up, promising results
were observed for the patients of grade II AVN where the progression of the disease was stopped [7]. Thus,
transplantation of mesenchymal stem cells may be a minimally invasive strategy for the treatment of femoral
head necrosis.
In this case report, we describe the treatment of avascular necrosis of the femoral head with bone marrow
and platelet concentrate.
CASE REPORT:
A 35 year old male patient came to our hospital with complaint of pain in left hip joint since 10 years. The
patient had intermittent pain radiating to his right groin and antero-medial thigh region. He also complained of
restricted hip movements with stiffness and mild pain in the lower back. History revealed that the patient had a
fall from stairs 15 years ago. No other relevant medical/surgical history was reported by the patient. The patient
had consulted an orthopedic surgeon who prescribed painkillers and nutritional supplements. However, relief
from symptoms was minimal and temporary.
21. A Journey From Pills to Cells | Dr Pradeep Mahajan | 21
On the patient’s first visit to our hospital,
complete clinical, hematological and radiological
investigations were done. Clinical scoring of the
patient’s condition was done based on Harris Hip
Score. A total score of 28 (poor) was calculated based
on range of motion scores and the findings of marked
pain, moderate limp, use of 2 canes/crutches, ability
to sit on a high chair for 30 minutes, inabllity to put
on shoes/socks and enter public transportation. Table
1 shows the range of motion values:
Table 1: degree of movement
FLEXION: 40 degrees
ABDUCTlON: 10 degrees
ADDUCTION: 10 degrees
EXT. ROTATION: 5 degrees
INT. ROTATION: 8 degrees
Radiological investigations [X-ray (Fig 1) and MRI
(Fig 2)] revealed:
• Marrow oedema in left femoral head, left
acetabulum,
• Small erosions in the acetabulum and
femoral articular margins,
• Thinning of articular cartilage and reduction
in joint space with synovial thickening.
A.P. view of pelvis with both hip joints reveal thal left
femoral head shows cortical irregularity of articular
surface with gross narrowing of left hip joint
space. The neck and the cortical head structure is
maintained inspite of irregular erosion as described
earlier. Osteopenia is visualized. Above findings are
suggestive of AVN of left femoral head.
Figure 1: XRAY of both hip joints showing AVN affected femoral head area (circled) dated 03-02-20I4
22. 22 | Dr Pradeep Mahajan | A Journey From Pills to Cells
Figure 2: MRl of the hip joint confirming AVN of the femoral head dated 03-02-2014
Based on the assessment, final diagnosis of Avascular
necrosis of the left femoral head (Stage II as per FICAT
and ARLET classification) was confirmed.
CLINICAL METHODOLOGY & TREATMENT PLAN:
On the basis of clinical findings the patient
was admitted for treatment in March 2014 and a
personalized treatment protocol was made based on
the severity of the condition and general factors such
as age of the patient, body mass index etc. The protocol
involved harvesting bone marrow concentrate, stromal
vascular fraction (SVF) from adipose tissue and platelet
rich plasma (PRP) from peripheral blood.
Bone marrow concentrate contains mixed
population of progenitor cells comprising of
mesenchymal and hematopoietic cells along with
mononuclear cells. Stromal vascular fraction isolated
from adipose tissue consists of endothelial cells,
adipocyte progenitors, immune cells, fibroblasts,
pericytes and stromal cells. Platelet rich plasma is a
platelet concentrate and a reservoir of cytokines and
growth factors. Vascular endothelial growth factor
(VEGF), fibroblast growth factor (FGF), platelet derived
growth factor (PDGF), transforming growth factor
(TGF-β). insulin-like growth factor (lGF) and epidermal
growth factor (EGF) that are present in PRP play an
important role in the healing process. Transplantation
dose was calculated on the basis of cell count and
grade of the disease.
23. A Journey From Pills to Cells | Dr Pradeep Mahajan | 23
RESULTS:
Following treatment, the patient was kept under
observation for 48 hours at the hospital. This was
a non-interventional period for homing of the cells
and for monitoring the general condition of the
patient. The patient was advised non weight bearing
physiotherapy exercises (passive) such as stretching
of the hamstrings, hip flexors and abductors followed
by range of motion exercises for the hip and knee.
Strengthening exercises were gradually instructed to
strengthen primarily the quadriceps, hip abductors and
hamstrings musculature. The patient was instructed to
continue the rehabilitation exercise programme for 1
year.
Follow-up was done periodically wherein clinical
and radiologjcal assessment was done. The patient
showed gradual improvement in clinical parameters of
pain and movements. Harris hip score calculation was
done at the 3rd
, 6th
and 12th
month follow-up. At the end
of the first year, the score was 89 (good). The patient
was free of pain within 6 months after treatment. The
patient is now able to walk unlimited distance without
using cane/crutches, can sit comfortably on any chair
and is able to enter public transportation.
Figure 3: One year post operative X-ray of the hip
joints dated 05/03/2015
CLINICAL LMPRESSION OF THE RESULT:
A.P view of pelvis with both hip joints reveals
right hip joint as normal and left hip joint showing
improvement in joint space (circled area) compared
to the pretreatment X-ray. The conical irregularity
of the articular surface of the femoral head shows
improvement. Osteopenia is visualized.
IMPRESSION:
Reduction in cortical irregularity noted.
DISCUSSION:
The common causes implicated in the etiology of
avascular necrosis of bone are corticosteroid use and
trauma which results in interruption of blood supply to
the area thus leading to necrosis of the bone. The other
causes of AVN may be systemic lupus erythematosus
(SLE), pancreatitis, alcoholism, gout, radiation, sickle
cell disease and infiltrative diseases (e.g. Gaucher’s
disease).
The occurrence of AVN among younger adults,
use of prosthesis and risk of surgery limit the
application of conventional treatment modalities such
as arthroplasty, core decompression etc. Cell based
therapy is thus gaining popularity as a non/minimally
invasive therapeutic modality in the treatment of
various disorders. The unique properties of stem
cells namely differentiation potential, self renewal,
anti-inflammation and immune-modulation aid in
regeneration of structures/tissues rather than repair
which commonly occurs after conventional/surgical
treatment modalities.
In our study, the cause of AVN was traumatic injury,
which possibly remained undetected in the initial
phase. After undergoing cell based therapy, the patient
showed gradual improvement with each follow-up
which reaffirms the positive effect of cell based therapy
in cases of avascular necrosis or femoral head.
Homing of stem cells is a complicated process
which involves an array of molecules. Necrosis of cells
induces the release of a series of signaling molecules, in
which specific receptors or ligands expressed in injured
tissues play an important role. Vascular endothelial
cells express a variety of adhesion molecules. Stem
cells are capable of adhering to these endothelial cells
and reach the site of ischemia. Studies have shown
that mesenchymal stem cells can not only migrate into
the femoral head, but also remain in the region for a
relatively long time.
The route of administration of cells also plays an
important role in the degree of improvement achieved.
In our study, the patient was administered intra-
articular and intravenous doses of mesenchymal stem
cells. In a study by Zhang-Hua Li et al., intravenous
administration of cells resulted in directional migration
of the cells to femoral heads to survive in the necrotic
environment. The rationale behind intra-articular
administration was to achieve higher concentration of
cells in the localized area. Nevertheless, further studies
24. 24 | Dr Pradeep Mahajan | A Journey From Pills to Cells
should be done to study the directional migration
of stem cells in order to formulate more specific
treatment protocols.
CONCLUSION:
This case report highlights the positive outcome of
cellular therapy achieved in a patient with avascular
necrosis of the femoral head. The patient withstood
the process fairly well with no obvious complications
or adverse reactions. The results are being maintained
(after 1 year) and has also resulted in an improvement
in the overall quality of life of the patient.
REFERENCES:
1. Ohzono K, Saito M, Sugano N, Takaoka K, Ono
K. The fate of nontraumatic avascular necrosis
of the femoral head. A radiologic classification
to formulate prognosis. Clin Orthop Relate Res
1992;277:73-8.
2. Lee MS, Chan YH, Chao EK, Shih CH. Conditions
before collapse of the contralateral hip in
osteonecrosis of the femoral head. Chang Gung
Med J 2002;25:228-37.
3. Steinberg ME, Hayken GD, Steinberg DR. The
‘conservative’ management of avascular necrosis
of the femoral head. In: Arlet J, Ficat PR, Hurgerford
DS, eds, Bone circulation, Baltimore: Williams and
Wilkins; 1984:334-7.
4. Tateishi-Yuyama E, Matsubara H, Murobara T,
et al. Therapeutic angiogenesis for patients with
limb ischaemia by autologous tranplantation
of bone-marrow cells: a pilot study and a
randomized controlled trial, Lancet. 2002 Aug.
10;360(9331):427-35
5. lkenaga S, Hamano K, Nishida M, et al. Autologous
bone marrow implantation induced angiogenesis
and improved deteriorated exercise capacity
in a rat ischemic hindlimb model. J Surg Res,
2001,96(2):217- 283
6. Herndon JH, Aufrane OE. Avascular necrosis of the
femoral head in the adult. A review of its incidence
in a variety of conditions. Clin Orthop Relat Res:
1972;86:43-62.
7. Hemigou P. Beaujean F, Treatment of osteonecrosis
with autologous bone marrow grafting. Clin
Orthop Relat Res. 2002;405:14-23.
25. A Journey From Pills to Cells | Dr Pradeep Mahajan | 25
RESEARCH PAPER
A study of Cell Therapy Assisted Regeneration of Cartilage in Avascular
Bone Necrosis.
Mahajan P. V., Bandre A.P., Desai N. S.
ABSTRACT:
Application of ‘regenerative medicine’ has
given a new hope to surgeons for the treatment
of several chronic diseases and disorders including
severe orthopedic conditions. There are a myriad of
orthopedic conditions and injuries that presently have
limited therapeutic treatments and could benefit from
new developing therapies in regenerative medicine
with the help of stem cells[1]
. Regenerative medicine
therapies are mainly based on the applications of
stem cells. Stem cells play a vital role in orthopedic
treatments and the studies have shown promising
results in repair of bones, tendons, cartilages etc.
Bone and cartilage regeneration ability of stem cells
has been demonstrated clinically; however success
rate may not be same in every case and it depends
on patient. Several factors can be responsible for
the same; including patient’s immune response, the
type and the grade of the disease which altogether
decide the fate of the treatment. In this paper, we
have presented some of the orthopedic case studies
performed through autologous transplantation of the
Stem cells.
Keywords: AVN (Avascular Bone Necrosis), ECM
(Extracellular Matrix), cytokines and chemokines,
bone marrow mononuclear cells, adipose tissue, PRP
(Platelet rich plasma)
INTRODUCTION:
Stem cells- known as the building blocks of the
body- represent unspeciallzed cells, which have the
ability to differentiate into different types of adult stem
cells. The differentiation depends on the type of the
stem cell and the niche. Niche and several signaling
pathways are responsible for the differentiation of the
stem cells into particular lineage of the cell[2, 3]
. Broadly,
stem cells are classified as ‘embryonic’ and ‘adult’
stem cells. Being truly pluripotent, embryonic stem
cells (ESC) can renew indefinitely and differentiate into
cells of all three germ layers thereby can regenerate
a part or even a complete organ[2. 3]
. Embryonic stem
cells are not easy to harvest and have many ethical
and legal issues associated so attempts were started
to induce pluripotency in somatic cells to make them
function like ESC’s. Takahashi and Yamanaka in 2006
first reponed the concept of induced pluripotent stem
cells (iPS cells)[4]
.
However because of the teratogenic potential
of induced pluripotent stem cells, the technique is
yet in the frame of question mark for its commercial
use in the mass[5, 6]
. However, in contrast, a variety of
multipotent adult stem cells exist in almost all tissues
of the organisms which reside in a specific niche in
vivo where various microenvironmental cues form
an intertwined signaling regulatory network that
maintains stem cells’ fate and functions. In this niche
there are different regulators such as ECM (Extra
Cellular Matrix) molecules, biochemical cues such as
soluble growth factors and cytokines and mechanical
cues such as intrinsic matrix stiffness and extrinsic
forces which play a major role in deciding the fate of
the stem cell.
Multipotent adult stem cells derived from bone
marrow also known as mesenchymal stem cells
are considered as the most competent stem cells.
These MSCs can be induced in vitro and in vivo to
differentiate into a variety of cell lineages including
bones, cartilages, tendons, muscles and other similar
tissues[7]
. However their differentiation into other
types of tissue-specific cells, such as cardiac myoblasts,
endothelial cells, hepatocytes and neural cells has also
been demonstrated in experimental studies[8, 9]
.
STEM CELLS IN THE TREATMENT OF ORTHOPEDIC
CONDITIONS:
Mesenchymal stem cells derived from bone
marrow are able to differentiate into different lineages
as they come in contact with specific niches. MSCs
are known to be capable of osteogenic, chondrogenic
differentiation. Bone marrow is aspirated from the
region of posterior superior iliac spine and the stem
cells are isolated and processed to prepare the dose for
the transplantation[10]
. Modern day orthopedics with
the use of cellular medicine for rejuvenarion therapies
looks promising and has overcome the traditional
surgical therapies. Traditional replacement therapies
involve the use of artificial joints with invasive
operative procedures which take longer time to heal
properly. There are numerous problems associated
with the use of biological grafts including donor site
morbidity, scarcity and tissue rejection. These types of
problems can be solved by using stem cell transplant
as they are based on less invasive applications of
cellular medicine. Most of the orthopedic problems
are because of degeneration of cartilage. When we
transplant mesenchymal stem cells locally, these cells
26. 26 | Dr Pradeep Mahajan | A Journey From Pills to Cells
try to move in the micro-environment of the bones
and tend to convert into osteogenic, chondrogenic
cells[11]
. These cells help in regenerating the damaged
area by forming new hyaline cartilage and bone. In
Non-unions, avascular necrosis (AVN), bone fractures
and bone defects, tendinitis and cartilage defects, stem
cells and regenerative medicine have a definite role.
BONE FRACTURES:
Bone has a natural tendency to reform when
fractured or damaged and while doing so it may
show development of fibrous cartilage. MSCs having
osteogenic potential tend to differentiate along the
osteogenic pathway in response to the niche factors
stimulation. Niche is usually composed of growth
regulators, cell adhesion molecules, niche cells and
extra cellular matrix which govern differentiation of
stem cells[11, 12]
. The process of entire regeneration
of bone at the damaged site after the application of
the stem cells can be dependent on factors like area
of dislocation or grade of the fracture. The cellular
medicinewiththeuseofgraftswasstudiedbyFernandez
Cl al. to study the effect of autologous bone marrow
mononuclear cells (BM-MNCs) on pseudarthrosis. They
concluded that by coupling autologous BM-MNCs and
allogenic bone graft one could constitute an easy, safe,
inexpensive and efficacious attempt to treat long-bone
pseudoanhrosis[13]. These studies showed how stem
cells are helpful in promoting union in cases of non-
unions when they are used alone or in combination.
STEM CELLS IN THE TREATMENT OF AVASCULAR
NECROSIS OF FEMORAL HEAD AND BENY GAPS:
Avascular necrosis (AVN) of femoral head is a
pathological process that results from interruption of
blood supply to the bone. Loss of vascularity means
the blood supply for these bones enters through
very restricted spaces & there is limited collateral
circulation which ultimately leads to death of
osteoeytcs and collapse of femoral head with change
in the shape of femoral head associated with pain, limp
and restriction of movements[14]
. The rate of avascular
necrosis of femoral head is found higher in young
patients following trauma, steroid intake, alcohol
consumption etc. Treatment options available till
date primarily focussed on reducing the intraosseous
pressure by drilling channels into the head through the
neck. In advanced disease, replacement arthroplasty
is commonly opted; but new surgeons are looking
forward to cellular medicine as an effective treatment
over traditional surgical procedures. Recently, Wang
et al. concluded bone marrow mononuclear cells
implantation as an effective procedure in patients
with early-stage AVN of femoral head[15]
. The additive
application of concentrated bone marrow aspirates,
ex vivo expanded mesenchymal stem cells, holds great
potential to improve bone regeneration[16]
. Similarly
using autologous mesenchymal stem cells from bone
marrow, Park et al and Zamzam et al have successfully
treated voids (gaps) in simple bone cysts[17, 18]
.
STEM CELLS TO TREAT CARTILAGE DEFECTS WITH
SCAFFOLDS:
Marcacci et al, used autologous MSCs used in
combination with hydroxyapatite scaffolds for filling
of cartilage defects and reported good integration
of the grafts[19]
. Cartilage once damaged has a very
poor ability ro repair itself; so application of new
chondrocytes at the damaged site may give rise
to formation of new hyaline cartilage. Autologous
chondrocyte transplantation has been used by Jager
cl al, to treat cartilage and bone defects[20]
. Abrasion
chondroplasty, in which drill holes are made into the
bone, showed good results with processed cells in
combination with biodegradable gels. Wakitani et al
used MSCs harvested from iliac crest in vitro and then
cultured in the lab for 1 month and then transplanted
them to the site of cartilage defect using collagen
gel and covered the defect with a periosteal flap[21]
.
Similarly Buda et al, reported the use of MSCs for the
treatment of osteochondral lesions of the femur and
talus[22]
.
All above findings make it very clear that stem
cells have the potential to treat several orthopedic
conditions due to their ability to get differentiated into
osteocytes, chondrocytes and muscle cells. Our study
further shows how patients got recovered from AVN by
using autologous chondrocyte transplantation.
MATERIALS AND METHODS:
Here we present some of the case studies
performed in the laboratory where application of
stem cells in the patients of AVN of femoral head
were performed. A prospective randomized trial on 15
patients of different age groups undergoing treatment
for AVN of femoral head was conducted (Table 1). All
of them underwent stem cell therapy by which stem
cells from their bone marrow and adipose tissue were
isolated in the laboratory; and later, after processing,
were injected back in the body. After taking the follow-
ups we found these patients were recovering and the
success ratio of recovery depends on various factors.
27. A Journey From Pills to Cells | Dr Pradeep Mahajan | 27
AVN in basically graded at 4 stages as per the Ficat
Staging
Stage 0
X-ray: normal
MRI: normal
clinical symptoms: nil
• Stage I
X-ray: normal or minor osteopaenia
MRI: oedema
bone scan: increased uptake
clinical symptoms: pain typically in the groin
• Stage ll
X-ray: mixed osteopenia &/or sclerosis &/or
subchondral cysts, without any subchondral
lucency
(crescent sign - see below)
MRI : geographic defect
bone scan : increased uptake
clinical symptoms: pain and stiffness
• Stage III
X-ray : crescent sign & eventual cortical collapse
MRl : same as X ray
clinical symptoms: pain and stiffness+/- radiation to
knee and limp
• Stage IV
X-ray: end stage with evidence of secondary
degenerative change
MRI : same as Xray
clinical symptoms: pain and limp
Table 1: No. of patients treated for AVN of Femur
head with Autologous Cell Therapy.
Subjects Sex Age BMI Stage Treatment
1 M 27 24.3 1
Autologous
Cell
Therapy
2 M 26 26.9 1
3 M 45 31 3
4 M 26 23 2
5 M 46 28.3 4
6 M 27 25 1
7 F 32 26 1
Autologous
Cell
Therapy
8 F 47 28.3 3
9 F 34 22 2
10 F 26 25 2
11 F 38 27.1 2
12 F 27 22 I
13 F 33 26 3
14 F 55 30.2 4
15 F 54 29.3 4
METHODOLOGY:
For all 15 patients case history was taken and all
were eligible for undergoing this treatment as per the
standard eligibility criterion confirmed after clinical
diagnosis. Consents were taken from all the 15 patients
at the time of their autologous stem cell therapy.
Followlng procedure was performed for every patient.
100 cc of bone marrow was taken from the iliac
bone of the patient with the help of a bone marrow
harvester in the medical facility and sample was sent to
the laboratory in an aseptic sterile condition. Similarly
100 cc peripheral blood was collected from the same
patient’s body and was sent to the laboratory in an
aseptic sterile condition. All samples were processed by
density centrifugation method to isolate mesenchymal
stem cells from bone marrow and adipose tissue in
separate batches[23]
. The isolated cells from bone
marrow were tested for cell count and cell viability
after which cells were characterized for MSC markers
CD73, CD90, CD105[24]
. Molecular characterization of
the processed cells confirmed their identity as MSCs.
Similarly isolated MSCs from adipose tissue were
tested for cell count and cell viability and molecular
characterization with CD13, CD29 confirmed their
identity[24]
. Collected peripheral blood was processed
and platelet rich plasma [PRP] was prepared. Bone
marrow & adipose tissue derived stem cells with
stromal factor were transplanted autologously along
with PRP. After 3 months, reports showed impressive
results in all these cases. Follow up was taken for a year
after every 3 months for individual patient. Patients
showed good improvement symptomatically with
following indications.
1. Clinical findings showed that knee pain, hip
pain reduced and mobility and flexibility or joint
increased than before.
2. Radiological findings: Restoration of joint space to
near normalcy, articular surface was well defined,
sub-articulor geodes were disappeared with signs
of new cartilage formation. (Figure 1)
28. 28 | Dr Pradeep Mahajan | A Journey From Pills to Cells
Figure 1. X-ray of a patient showing improvement in
terms of bone growth difference after treatment.
X-Ray Fums Showing Bone Growth Difference
Role of Niche in stem cells differentiation and
proliferation
X-ray taken after 3 months follow up of the patient
showedsignsofnewcartilageformationwhichindicates
the process of chondrogenesis. Studies have shown
that the microenvironmeet - also known as ‘niche’
comprised of ECM (extracellular matrix), regulators,
chemokines and cytokines play an important role in
chondrogenicdifferentiation.TGFBs,IGFsandFGFshave
been implicated in chondrogenesis[24]
. Besides the cell-
cell signaling, cell-matrix interactions can also alter cell
behavior and thus influence the commitment of MSCs
into chondrocyte Iineage[25, 26]
. Along with the above-
discussed applications of stem cells at our laboratory,
some other conditions are also being investigated for
their suitability for stem cell applications including
ankylosing spondylitis, bone fractures, non healing
fractures, osteoarthritis, sports injuries. Though
application of stem cells is well proven in orhopedic
conditions, the therapy also looks promising for other
neurological and metabolic disorders and clinical for
which clinical trials are being performed worldwide[27]
.
SUMMARY:
Stem cell therapy based on the principle of the
regenerative medicine is an attractive option for the
treatment of intractable diseases. However, the use
of stem cell therapy in all the conditions discussed
above is subject of individual treatment. Many of these
studies have shown quick good results but at the same
time few cases have shown slow improvement in the
conditions.Asdiscussedearlier,thismightalsobelinked
to the selection of the patient, the type of cells used,
concentration and dose of the cells used, application of
cells, duration of follow up and evaluation tools among
others. Many more long term prospective randomized
human trials need to have good results before one may
actually recommend the use of these cells. It is certain
that the future is going to be exciting with the use of
stem cells. A paradigm shift from conventional mode of
treatments to the novel stem cell therapy is the need of
the modern healthcare. High quality research coupled
with practical applications in the cellular medicine has
set a stage for successful tissue engineering in vitro.
Stem cell therapy has brought in a lot of optimistic
hope amongst researchers, doctors and but obviously
the patients. At the same time, establishing the safety
profile of these therapies is equally important to
avoid complications as there is a strong demarcation
between hype and hope regarding the potential use of
these therapies.
REFERENCES:
1. Kaiser LR. The future of multihospilal systems. Top
Health Care Finance 1992. Summer; 18(4):32-45.
2. Anderson DJ. Gage FH, Weissman IL. Can stem
cells cross cell lineage boundaries? Nat Med. 2001
Apr:7(4):393-5.
3. Ehnert S, Glanemann M, Schmitt A, Vogt S,
Shanny N, Nussler NC. The possible use of stem
cells in regenerative medicine: dream or reality?.
Langenbecks Arch Surg 2009 Nov: 394(6):985-97.
4. Takahashi K, Yamanaka S. Induction of pluripotent
stem cells from mouse embryonic and adult
fibroblast cultures by defined factors. Cell 2006
Aug; 126(4):663-76.
5. Rodolfa K. Di Giergio FP. Sullivan S. Defined
reprogramming: a vehicle for changing the
diffarentiated state. Differentiation 2007 Sep;
75(7):577-9.
6. Mafi R. Hindocha S, Mafi P, Griffin M, Khan
WS. Sources of adult mesenchymal stem cells
applicable for musculoskeletal applications-a
systematic review of the literature. Open Orthop
J 2011 (5 Suppl 2):242-8.
7. Ohgushi H, Caplan AI, Stem cell technology and
29. A Journey From Pills to Cells | Dr Pradeep Mahajan | 29
bioceramics: from cell to gene engineering. J
Biomed MaterRes 1999:48(6);913-27.
8. Kotobuki N. Hirosc M, Takakura Y, Ohgushi H,
Cultured autologous human cells for hard tissue
regeneration: preparation and characterization of
mesenchymal stem cells from bone marrow. Artif
Organs 2004 Jan; 28(1);33-9
9. Proekop, D.J. (1997). Marrow stromal cells as stem
cells for non-hematopoietic tissue. Science276,
71-74
10. Hernlgou P, Mathieu G, Poignard A, Manicom O,
Beaujean F, Rouard H. Percutaneous autologous
bone-marrow grafting for nonunions. Surgical
technique. J Bone Joint Surg Am 2006 Sep; 88
Suppl 1(Pt2)322-7.
11. Hernigou P, Poignard A, Beaujean F, Rouard H.
Percutaneous autologous bone marrow grafting
for nonunions. Influence of the number and
concentration of progenitor cells. J Bone Joint Surg
Am. 2005 Jul; 87(7):1430-7.
12. Burwell RG. The function of bone marrow in the
incorporation of a bone graft. Clin Orthop Relar
Res. 1985 Nov; 200: 125-41.
13. Fernandez-Bances I. Perez-Basterrechea M, Perez-
Lopez S, Nuilez Batalla D, Fernandez Rodriguez
MA, Alvarez Viejo M et al., Repair of long-bone
pseudoarthrosis with autologous bone marrow
mononuclear cells combined with allogenic bone
graft. Cytotherapy. 2013 May; 15(5):571-7.
14. Sen RK. Management of avascular necrosis of
femoral head at pre-collapse stage. Indian J
Orthop. 2009 Jan; 43(1):6-16.
15. WangT,WangW,YinZS.Treatmentofosteonecrosis
of the femoral head with thorough debridement,
bone grafting and bone-marrow mononuclear
cells implantation. Eur J Orthop Surg Traumatol,
2013 Jan.
16. Sen RK, Tripathi SK, Aggarwal S, Marwaha N,
Sharma RR, Khandelwal N. Early results of core
decompression and autologous bone marrow
mononuclear cells instillation in femoral head
osteonecrosis: a randomized control study. J
Arthroplasty, 2012 May; 27(5):679-86.
17. Park IH, Micic ID, Jean IH. A study of 23 unicameral
bone cysts of the calcaneus: open chip allogeneic
bone graft versus percutaneous injection of bone
powder with autogenous bone marrow. Foot
Ankle lnt. 2008 Feb; 29 (2); 164-70.
18. Zamzam MM, Abak AA, Bakarman KA. Al-Jassir FF,
Khoshhal KJ, Zamzami MM. Efficacy or aspiration
and autogenous bone marrow injection in the
treatment of simple bone cysts. Int Orthop, 2009
Oct;33(5): 1353-8.
19. Marcacci M, Kon E, Moukhachev V, Lavroukov A,
Kutepov S, Quarto R, et al. Stem cells associated
with macroporous bioceramics for long bone
repair: 6 to 7 year outcome of a pilot clinical study.
Tissue Eng. 2007 May; 13 (5):947-55.
20. Jiger M. Jelinek EM, Wess KM, Scharfstadt
A, Jacobson M, Kevy SV. et al. Bone marrow
concentrate: a novel strategy for bone defect
treatment. Curr Stem Cell Res Ther, 2009 Jan;
4(1):34-43.
21. Wakitani S, Nawata M, Tensho K, Okabe T, Machida
H, Ohgushi H, Repair of articular cartilage defects
in the patellofemoral joint with autologous bone
marrow mesenchymal cell transplantation: three
case reports involving nine defects in five knees.
J Tissue Eng Regen Med. 2007 Jan-Feb; 1(1):74-9.
22. Buda R, Vannini F, Cavallo M, Grigolo B, Cenacehi
A, Giannini S. Osteochondral lesions of the knee:
a new one-step repair technique with bone-
marrow-derived cells. J Bone Joint Surg Am. 2010
Dec.;92 Suppl 2:2-11.
23. Than RS, Boland G, Tuli R. Adult mesenchymal stem
cells and cell-based tissue engineering. Arthritis
Res Ther 2003: 5:32-45. .
24. Mitchell JB, Mclntosh K. Zvonic S et al.
Immunephenotype of human adipose-derived
cells: temporal changes in stromal-asseciated and
stem cell-associated markers. Stem Cells 2006; 24:
376-85.
25. Dominici M. Le Blanc K. Muellcr I, et al. Minimal
criteria for defining mulrlporent mesenchymal
stromal cells, The International Society for Cellular
Therapy position statement. Cytotherapy 2006;
8:315-317.
26. Goessler UR, Bugert P, Bieback K, et al. In-vitro
analysis of the expression of TGFbeta-superfamily-
members during chondrogenic differentiation of
mesenchymal stem cells and chondrocyres during
dedifferentiation in cell culture. Cell Mol BioI Lett
2005; 10; 345-362.
27. Tripathy SK, Behera P, Sen RK, Goyal T. Application
of stem cells in orthopaedlc conditions: what is
the current evidence? OA Orthopaedics 2013 May
01;1(1):3
30. 30 | Dr Pradeep Mahajan | A Journey From Pills to Cells
Changing Paradigms in Healthcare Medicine
Pradeep v. Mahajan1*
, Anurag P. Bandre1
, Nitin S. Desai1
1. Chairman and Managing Director, StemRx Bioscience Solutions Pvt Ltd., R-831,T.T.C.,
Thane Belapur Road, Rabale, Navi Mumbai, Maharashtra, India
*Corresponding Author and Address: Dr. Pradeep V. Mahajan,
StemRx Bioscience Solutions Pvt. Ltd., R-831, T.T.C., Thane Belapur Road,
Rabale, Navi Mumbai, Mahatarashtra, India. Email: drpvmahajan@gmail.com
ABSTRACT:
The science of healthcare medicine is changing rapidly and coming out of its shell with better prospects. The
healthcare sector is now not just limited to the old concept of one pathogen causing one disease and treated
by one medicine; but it is being replaced by the application of newer treatment modalities to treat diseases and
disorders. The concept of donor organ transplant is now changed to concept of organ regeneration (using IPSCs-
induced pluripotent stem cells or even using autologous stem cells). Regenerative Medicine has played a big role
in this paradigm shift. The Regenerative medicine - a branch of translational research uses stem cells in tissue
engineering and molecular biology which deals with the process of reengineering or regenerating human cells,
tissues or organs at the defective sites to restore or establish normal function. The applications of Regenerative
Medicine are worldwide and it is now important to enhance the efficacy of these appications by merging the
distinguishing field of science using the variables those can change the paradigms of regenerative medicine.
Keywords: Regenerative medicine, stem cells, IPSCs, organ regeneration
INTRODUCTION:
Stem cells are not new to us and we all know
the importance of therapeutic applications of the
stem cells in different diseases and disorders but we
are also aware of the fact that stem cell therapy has
sparked much controversy over the last several years;
as this field is still surrounded by ethical, legal, political
and social barriers. Safety and efficacy issues in use of
stem cells have raised the concern about their use in
the treatment of different diseases and disorders. But
if these issues are properly taken care of, stem cells
can play the role of wonder drug in modern medicine.
Most of the medical experts are aware of the fact that
old and conventional medical therapies have proven
to be ineffective and useless for many of the dreadful
diseases. In such cases, where people are asked to
compromise with their health condition, stem cells
can really prove a medicinal boon to such patients.
The regenerative medicine market has already started
encroaching European and US countries with stem
cell products, therapies and technologies. There is
no doubt that the upcoming era will be of cellular
medicine with more and more treatment modalities. As
shown in Fig.1, it is clear how fast this parallel science
of regenerative medicine is showing its potential in
the global healthcare market. What requires now
is to understand its wide scope and to focus on the
usefulness of this science in the mass.
Regenerativemedicinebasedontheapplications
of stem cells comprises a market for regenerative
products and can be seen growing exponentially in the
coming years. Stem cells have wide use in the treatments
of orthopedic conditions, neurodegenerative conditions,
cardiovascular diseases and even several chronic
metabolic disorders. Other disorders that will benefit
from cell therapies include diabetes, inflammatory
diseases and aging disorders. The success ratios may vary
with respect to disease condition and the type of therapy
used. Many a times it is seen that efficacy of treatment
is dependent on the allied treatment modalities coupled
with the main stem cell therapy.
31. A Journey From Pills to Cells | Dr Pradeep Mahajan | 31
Fig 1. (Source: Report #S520, “Tissue Engineering, Cell Therapy and Transplantation: Products, Technologies &
Market Opportunities, Worldwide, 2009-2018.”)
These variables may play an important role in
deciding the fate of stem cell therapy in controlling the
signs and symptoms of the disorders.
THE VARIABLES OF CHANGING PARADIGMS FOR
REGENERATIVE MEDICINE:
The distinguishing fields of allied treatment
modalities which can really revamp the regenerative
medicine comprise of game changing technologies
like robotic medicine, telemedicine, digital medicine,
genomic & molecular medicine and nanomedicine.
STEM CELLS AND ROBOTIC MEDICINE:
Stem cells are the repairing kits which we carry in
our body. There are many sources of stem cells like
cord blood, cord tissue, bone marrow, adipose tissue
which can be used for therapeutic applications. In
autologous cellular treatment patients own body cells
are transplanted back after processing them in vitro.
Robotic medicine is not new to health care. We all
are aware of the Vinci Surgical System that arose in
2000. Robotic system has eased the complex surgeries
and is based on high end mechanics. In regenerative
medicine, stem cell harvesting procedures and
transplant procedures can definitely be coupled with
the use of robotic arms; and set the new perfections.
Recently in 2014 Bollinger M, Wechsler L and Stein
J, in their studies have concluded that robotics,
stem cells and brain computer interfaces all have
tremendous potential to reduce disability and lead to
better outcomes for patients with stroke [1]. However
continued research and funds will be required to
strengthen these fields as merging capacities of these
sciences are still in a nutshell.
STEM CELLS AND TELEMEDICINE OR DIGITAL
MEDICINE:
The wireless innovations in healthcare have
revolutionized the concept of remote consultations.
Using high end technologies and advanced ways of
communication,nowit’spossibletotransferthemedical
information through audiovisual media. With the use of
Google mirror, holographic consultations are possible
indoors, sitting at home, virtual medical visits and
holographic consultations have made communication
easy; and will be the milestone for creating awareness
about the importance of regenerative medicine in
mass. The cost effective and time saving parameters
further add to the importance of this area. Digital
medicine is a multidisciplinary subject that arose with
the merging of medicine and new digital technologies;
and covers subjects such as medicine, mathematics,
informatics, electronics and mechanical engineering. It
can be used for basic research, clinical studies and for
the treatment of various diseases [2]. Zhu Weifun et al
in 2014 has shown the importance of telemedicine and
digital management in repair and regeneration after
nerve injuries and other nervous system diseases [3].
STEM CELLS AND NANOMEDICINE:
32. 32 | Dr Pradeep Mahajan | A Journey From Pills to Cells
Nanotechnology allows scientists to create, explore
and manipulate nonmaterial measured in nanometers
which can be used in advanced surgeries. The clinical
potential of targeted nanomedicine delivering to
cancer stem-like cells is now world known as Sang-Sec
Kim et al have shown the Importance of nanomedicine
treatments on cancer patients for the delivery of stem
cells. They developed a tumor-targeting nanodelivery
platform (scL) for systemic administration of molecular
medicines. In various animal models, post treatment
with the scl, nanocomplex carrying various payloads,
they observed exquisite tumor-targeting specificity
and significant antitumor response with long-term
survival benefit [4].
STEM CELLS AND BIOENGINEERING:
Regenerative medicine also includes use of
biodegradable scaffolds with stem cells and their
safe implantation at the defective sites. Combining
stem cells with biomaterial scaffolds provides a
promising strategy for engineering tissues and cellular
delivery. Biomaterials can be natural or synthetic,
protein based or polysaccharide based. Protein based
natural biomaterials are collagen, silk and fibrin
while polysaccharide based natural biomatertals are
agarose, alginate, hyaluronan and chitosan. Synthetic
biomaterials include PLGA (poly lactic-co-glycolic
acid) and PEG (poly ethylene glycol). The type of the
biomaterial or the cues used, play an important role
in deciding the fate of the stem cells implanted. Stem
cells along with these biomaterials have been used in
many treatment modalities for orthopedic conditions
like cartilage repair, bone fractures, tendon injuries and
many more. Besides orthopedic conditions, stem cells
with scaffolds have proven their efficiency in cosmetic
surgeries and even cardiac operations. Cell sheets of
MSCs (mesenchymal stem cells) have shown to improve
cardiac function when used with collagen [5].
ORGAN DEVELOPMENT WITH 3D PRINTING
TECHNOLOGY:
Tissue engineering technology promises to solve
the organ transplantation crisis. The assembly of
vascularized 3D soft organs remains a big challenge.
Organ printing defined as computer aided, jet based
3D tissue-engineering of living human organs offers a
possible solution. Organ printing involves development
of blueprints for organs followed by actual organ
printing and organ conditioning. Cell printers that
can print gels, single cells and cell aggregates have
been developed. Solidified thin layers of sequentially
placed, thermo-reversible gel serves as printing paper.
Combination of engineering approach with embryonic
tissue fluidity concept of developmental biology
enables the creation of a new rapid prototyping 3D
organ printing technology, which has the potential to
accelerate and optimizethe tissue and organ assembly
dramatically [6]. 3D printing technologies are already
being used in pharmaceutical research and fabrication,
and look promising in bringing transformation.
Advantages of 3D printing include high reproducibility,
precise control of droplet size and dose and the ability
to produce dosage forms with complex drug-release
profiles.
Complex drug manufacturing processes can also be
standardized through the use of 3D printing to make
them simpler and more viable. 3D printing technology
could also prove beneficial in the development of
personalized medicine [7].
REVAMPING OF HEALTHCARE SECTOR:
Regenerative medicine coupled with all the above
mentioned advancements and can revamp the entire
healthcare sector. During this happening the paradigm
of healthcare has shifted towards cellular medicine
from the old conventional medicine. In the due course
of time surgeons have done number of successful
transplants with the help of stem cells. For an instance,
hip replacement is taken over by hip regeneration
and instead of spending millions of dollars on insulin
injections,nowitispossibletoregenerateinsulinfactories
in vivo to eliminate diabetes completely [8]. Similarly in
several orthopedic conditions, neurodegenerative and
neuro developmental conditions, stem cell treatments
have proven their existence. In the coming years
researchers may introduce ‘stem cell gene therapy’
for immunomodulatory treatments in autoimmune
disorders. GroundbreakinginventionofTcellseducator
therapy for autoimmune disorders by Dr. Yong Zhao [9]
as highlighted by the American Diabetes Association at
72nd
Scientific Sessions (Philadelphia, 2012) is one of
the 8 major breakthroughs and initiatives which were
done in 2012. Stem cell growth and migration on nano-
33. A Journey From Pills to Cells | Dr Pradeep Mahajan | 33
fibrous scaffolds and micro-fluidic channels on silicon
chip were studied using neural stem cells isolated from
adult rats. Possibly this technology of using neural
stem cells will revolutionize the treatment protocols in
electrical signal neural transmission system [10]. The
invention of VSELs (Very small embryo like stem cells) or
DCs (dendritic cells) have already raised the standards
of treatment modalities in cancer medicine [11].
DISCUSSION:
Science is so evolved that the concept of developing
a body organ which looked like dream once upon
a time is no more fiction; but has turned into reality
with the help of 3D printing and scanner technology.
Now it is possible to develop organs like liver, kidney
etc. This clearly indicates that regenerative medicine
is the future of medicine and conceptually the day
is no far when one can access the organ shops easily
in healthcare market. However this field is under
siege politically and financially, so it needs an urgent
attention to promote this science which has true
powers of revamping the complete healthcare sector.
Medical technology is growing rapidly. Several diseases
can now be treated very effectively with the application
of implantable devices that restore physical and
mechanical function, such as replacement of hip joints
or restoration of heart rhythms by pacemakers. The
techniques, however, are rather limited; and biological
function cannot be restored through the use of inert
materials and devices. Patients today demand quality
health care and health care practitioners demand
stability which has to be taken care of; otherwise it
will lead to the problem of health crisis. This may
lead to legislation expanding the scope of practice for
allied health care providers, thereby circumventing
physicians and undermining our control. If we really
want to avoid the health crisis problem, revamping
of healthcare medicine is necessary and globally it
requires an urgent attention to step towards a better
healthcare system.
REFERENCES:
1. Bollinger ML, Wechsler LR, Stein J. Robotics,
stem cells, and brain-computer interfaces in
rehabilitation and recovery from stroke: updates
and advances. Am J Phys Med RehabiI. 2014; 93
(11 Suppl 3):S145-54.
2. Wang LS, Luo YR. Digital medicine and digital
orthopedics: a hot topic in tissue engineering.
Zhongguo Zuzhi Congcheng Yanjiu Vu Lichuang
Kangfu, 2008; 12:6374-6380.
3. Zhu W, Zhai Y, Sun D, and Zhao J. Telemedicine and
digital management in repair and regeneration
after nerve injury and in nervous system diseases.
Neural Regen Res. 2014; 9(16); 1567-1568.
4. Kim S, Rait A, Rubab F, Rao AK, Kiritsy MC, Pirollo
KF, Wang S, Weiner LM and Chang EH. The clinical
potential of targeted nanomedicine: Delivering to
cancer stem-like cells. Molecular Therapy 2014;
22(2):278-291.
5. Miyahara Y, Nagaya N, Kataoka M, Yanagawa B,
Tanaka K, Hao I-L Ishino K, Ishida H, Shimizu T,
Kangawa K, Sano S, Okano T, Kitamura S, Mori
H. Monolayered mesenchymal stem cells repair
scarred myccardium after myocardial infarction,
Nat Med 2006 12:459 - 465.
6. Murphy SV and Atala A. 3D bioprinting of tissues
and organs. Nature Biotechnology - 2014; 32, 773-
785,
7. Ursan I, Chiu L, Pierce A. Three-dimensional drug
printing: a structured review. J Am Pharm Assoc.
2013;53(2):136-144
8. Pagliuca FW, Millman JR, Gurtler M, Segel M,
Dervort AV, Ryu JH, Peterson QP, Greiner D and
Melton DA. Generation of Functional Human Pan-
creatic β Cells In Vitro. Cell. 2014;159(2):428-39
9. Yong Zhao, Stem Cell Educator Therapy and
Induction of Immune Balance. Curr Diab Rep.
2012;12(5):517-23.
10. Geng Z, Du J, Zhang L, Yang C, Wang W and
Li Z (2010). Separation And Enrichment Of
Mesenchymal Stem Cells On A Chip, In 14th
International Conference on Miniaturized Systems
for Chemistry and Life Sciences; Groningen, The
Netherlands
11. Nagaraj S, Ziske C and Schmidt IGH. Dendritic cell,
the immunotherapeutic cell for cancer. Indian J
Med Res 2004;119, 133-138
34. 34 | Dr Pradeep Mahajan | A Journey From Pills to Cells
64. 64 | Dr Pradeep Mahajan | A Journey From Pills to Cells
Success stories those created
history
INAYA CHAVAN (CEREBRAL PALSY)
CASE HISTORY
Baby Inaya Chavan was born in January 2015 as a normal child
with low birth weight.
In the first week after the birth, her wrists got bent and her feet
started pointing downwards. At about 3 months of age, her
eye and neck movements started becoming jerky and random.
When the pareants consulted their family doctor, basic medications and nutrient supplements
were prescribed. At 6 months of age, she suffered from an epileptic attack. Later on, she started
getting seizures anytime during the day. She continued to have epileptic episodes since then.
Inaya could not move or lift her legs.
STEMRX TOUCH
For Dr. Mahajan this was an extremely challenging case as the baby’s age was very less.
Investigation was done to understand her condition for the treatment. 3 sessions of cell therapy
were suggested for her over a period of 21 days. Fortunately, Inaya started responding quickly.
After three sessions, she exhibited tremendous improvement in her condition and started
responding to voice commands with improvement in her eye movements.
TESTIMONIAL (Mrs. Namrata Chavan)
“We visited many hospitals like Hinduja, KEM, JJ etc. and we were told that our baby is abnormal.
I had become nervous to hear this. But God’s grace, we got a chance to meet Dr. Mahajan, he
relieved us by stating that our baby is not abnormal and assured us to treat her. After treatment,
she showed drastic changes.”
SUSHANT CHAVAN (MULTIPLE SCLEROSIS)
CASE HISTORY
An engineer from Sangli, Sushant Chavan was suffering from bodyache for five years. During his
education, his health was deteriorating slowly and finally he got completely bedridden. After
a medical test, in October 2011 he was diagnosed with multiple sclerosis which shattered his
family.
STEMRX TOUCH
While going through this tough situation, his family heard about StemRx and they decided to
visit here to consult Dr. Mahajan. Doctor, after evaluating Sushant’s physical condition, started
the treatment immdiately. Within 2 months of the first stage of treatment, his body started
responding well. Now he can write and speak. He also can walk by taking support.
TESTIMONIAL
“I was not able to move at all. I had to depend upon others even for carrying out daily activities.
I had started losing my courage and even my hope. But I came across an article by Dr. Pradeep
65. A Journey From Pills to Cells | Dr Pradeep Mahajan | 65
Mahajan and my family contacted him. Now I am feeling better and my health is getting improved fast.
Now I am extremely happy being able to start my studies again.”
HEDAYATULLAH (ANKYLOSING SPONDYLITIS) (https://www.youtube.com/
watch?v=ks4wN0d9bIo&feature=youtu.be)
CASE HISTORY
Hedayatullah from Afghanistan was suffering from Ankylosing Spondylitis since 12 years. He was
having pain throughout his body from neck to lower back and all the joints. He came to know about
StemRx and Dr. Mahajan through internet. Dr. Mahajan assured him to treat his ailment and asked him
to come to India for the treatment as soon as possible.
STEMRX TOUCH
When he visited StemRx, the treatment plan was decided. After the treatment started, his backpain
got 90% cured. Even his dependency on painkillers came to stop.
TESTIMONIAL
“I am about 90% ok. I was having about 20 painkillers every day for backache as well as joint pain. Now
I have stopped taking painkillers and still there is no pain. I am extremely thankful to Dr. Mahajan.”
JAGANNATH BHAVARE (https://www.youtube.com/watch?v=mBgOnWd5UUk&-
feature=youtu.be)
CASE HISTORY
Jagannath Bhavare’s ailment began with sudden pain in lower back. All the doctors consulted insisted
upon operation which forced him to get that done. However, after operation, he started suffering from
stoppage of urination. While treating this, he got infection. This was diagnosed to be due to damage
to the nerve happened during the previous operation. The series of health problems occured this way
compelled him to search for a doctor who would assure complete cure, when he read about StemRx
in newspaper.
STEMRX TOUCH
After evaluation and start of treatment, within a shockingly short span of 2 days his urine flow got
normalised. His dependency on catheter came to end.
TESTIMONIAL
“I had to use catheter and plastic bags while passing urine. After stem cell therapy, the urine flow was
completely normalized.”
ARUN LAKHANI (BILATERAL AVN) (https://www.youtube.com/watch?v=k-
s4wN0d9bIo&feature=youtu.be)
CASE HISTORY
Arun was suffering from bilateral AVN. In his left hip joint he was suffering from third degree AVN and
right hip joint form second degree AVN. Orthopedic surgeons had suggested him total hip replacement
surgery. But he was reluctant to do that considering his younger age. He learnt about stem cell
treatment and Dr. Pradeep Mahajan through internet.
66. 66 | Dr Pradeep Mahajan | A Journey From Pills to Cells
STEMRX TOUCH
After treatment the pain got completely cured and the person is able to walk properly.
TESTIMONIAL
“After the treatment, I am happy and my pain is gone. Thank you so much Dr. Pradeep Mahajan.”
MOHAMMAD SHAHID (ANKYLOSING SPONDYLITIS) (https://drive.google.com/
file/d/0B7_h4U343DRCNWJTUVhxaGg4R0k/view)
CASE HISTORY
Mohammad Shahid was suffering from Ankylosing Spondylitis. He was having unbearable pain and
difficulty in moving his neck.
STEMRX TOUCH
With stem cell therapy he got relief from pain. Now he is able to rotate the neck freely.
TESTIMONIAL
“I have been taking treatment from so many places, but this therapy worked well for me. The pain is
gone and movement is improved.”
SAJJAD (TYPE 1 DIABETES) (https://drive.google.com/file/d/0B7_h4U343DRCNFF-
pZ3JTODctOHc/view)
CASE HISTORY
Sajjad, a medical student from Iraq was suffering from type 1 diabetes since 15 years. He had to take
insulin, still his diabetes was not controlled. The blood sugar level was 250-300. He came to know about
StemRx and Dr. Mahajan while searching on net.
STEMRX TOUCH
StemRx suggested him some lifestyle modifications and physiotherapy alongwith the regular treatment.
After 15 days there was improvement in the overall condition of the patient.
TESTIMONIAL
“I am very happy to see the improvement. Previously I had so much weakness but now I feel better.”
TRISHA KULKARNI (LICHEN PLANUS) (https://drive.google.com/file/d/0B7_
h4U343DRCUnZzc01xeFF2ZUk/view)
CASE HISTORY
Trisha was suffering from lichen planus(skin rash which itches a lot and then converts to black spots)
since the age of 10 years. She tried all sorts of medicines : alopathy, ayurvedic as well as homeopathic.
She came to know about StemRx through net.
STEMRX TOUCH
After 3 treatment sessions she saw major changes in the appearance of her skin. The itching was gone
and skin started becoming normal.
TESTIMONIAL
“I am very happy for the treatment and I’m sure Dr. Mahajan will get me cured completely.”
67. A Journey From Pills to Cells | Dr Pradeep Mahajan | 67
DR. ADITI THORAT (MENORRHAGIA) (https://mail.google.com/mail/u/0/#inbox
/1572d7035bc71239?projector=1)
CASE HISTORY
Aditi was suffering from menorrhagia induced by PCOD(polycystic ovary syndrome). She was also taking
treatment for hypothyroidism. She was showing many symptoms including hypertension, palpitations
and breathlessness. Menorrhagia had led to dropped haemoglobin level and a lot of emotional stress.
With medication and pills, her haemoglobin levels got normalised, still the underlying problem of
menorrhagia could not be cured completely.
STEMRX TOUCH
Within a period of 10 days, that is from 10th
November to 20th
November, her periods as well as
emotional state, both got improved. She beat breathlessness
TESTIMONIAL
“I feel energetic the way I used to be when I used to be in college. I am having more and more positive
thoughts. I am trying to overcome things and it’s coming on its own. The therapy is amazing! ”
PATRICK (EMPTY NOSE SYNDROME) (https://www.youtube.com/watch?v=mB-
gOnWd5UUk&feature=youtu.be)
CASE HISTORY
PatrickfromAustraliawassufferingfromemptynosesyndromesince6years.Theendoscopicevaluation
showed the inferior turbinate on left completely eroded.
STEMRX TOUCH
Dr. Mahajan prepared a totally customized protocol by using self limiting scafolds, autologus cells
and growth factors. After a week endoscopy showed improved vasculature. Patient experienced a
remarkable difference in breathing sensation with first week of treatment itself.
TESTIMONIAL
“For almost 6 years, I was feeling depressive due to empty nose syndrome. We had approached lot
many doctors in last 6 years. It was a great decision to come to India for treatment. Dr. Mahajan and his
team cooperated very well and made my treatment possible.”