Stem cell medicine

1. Presented by
Dr Ajith Y. MVSc
Division of Medicine
IVRI, Izatnagar, UP, India

2. The
Future medicine

3. An undifferentiated cell of a multi cellular
organism, which is capable of giving rise to
indefinitely more cells of the same type and, able to
differentiate into specialised cells in the body.

4. a) Self renewal:
Maintain undifferentiated population
b) Potency:
Ability to differentiate to cell types
Totipotent eg: Morula cells
Pluripotent eg: Inner cell mass
Multipotent eg: Hematopoetic stem cell
Oligopotent eg: Myloid stem cell

5. a) Embryonic stem cell
Inner cell mass of blastocysts
Ectoderm, endoderm and mesoderm
b) Extra embryonic stem cell
Placental fluids (Amniotic)
Umbilical cord blood
c) Adult stem cell
Bone marrow; Adipose tissue; Blood
Repair and replenishing adult tissues

7.  1908: term “stem cell”- Russian histologist- Alexander
Maksimov
 1968: First bone marrow transplant: Immuno deficiency
 1981:Isolation of a embryonic stem cell line from mouse
(Evans et. al.)
 1991: Stem cell regeneration of tissues (uterus, fallopian tube,
hernia) and patented (Dr. B.G. Matapurkar)
 1998: Human embryonic cell line derived
( J A Thomson et. al.)
 2000: Placed into non immunogenic material to prevent rejection
(Shapiro, J)

8. Korean researcher
Hwang Woo Suk
human embryonic stem cell lines
from human Oocytes

9.  2006: Umbilical cord derived stem cells discovered
(Y. Zhao et. al.)
 2006: Induced pluripotent stem cell in mice
(S Yamanaka et. al)
 2007: Isolation of amniotic stem cell line at Harward
university
 2007: Somatic cell nuclear transfer
(S. Mitalipov et. al.) & (J. Yu et. al.)
 Oct 2010: First trial of embryonic stem cells in humans
(Geron co.)

10. Induced pluripotent Stem cells
From adult fibroblast
( nobel prize for Physiology/
Medicine , 2012 )
S Yamanaka

11. A) Donor Recipient relation
Autologous stem cell therapy
 Isogenic or Syngenic stem cell therapy
 Allogenic stem cell therapy
 Xenogenic stem cell therapy
B) Source of stem cell
 Embryonic stem cell
 Umbilical cord blood derived/ Amniotic stem cell
 Induced pluripotent stem cell
 Adult stem cell

12. Steps in stem cell
therapy...
1. Isolation
2. Culturing
3. Disaggregation
4. Passaging
5. Characterisation
6. Differentiation
7. Transplantation
8. Monitoring

14. Bone marrow collection sites

16. Diabetes mellitus
Duct cells from adult human pancreatic tissue- induced to
differentiate into ductal and endocrine cells.
(Bonner-Weir S.et al:2000)
Placed into non immunogenic material to prevent rejection
(Shapiro. J, 2000)
Parkinson’s disease
Embryonic stem cells – improvement in condition - teratoma
(Sonntag et al. 2006 )
Mesenchymal SCs- 7 human Parkinson patients- improvement in
symptoms - without any side effects.
(Venkataramana et al, 2010)
Induced PSC - rat model - behavioural improvement - tumors.
(Wernig et al. in 2008)

17. Alzheimer’s disease
Neural stem cells of hippocampus –mice - increase in cholinergic
neurons - cognitive ability improved
(Xuan etal,2009)
Mesenchymal stem cells- human umbilical cord blood – mouse
(H.J.Lee et al:2010)
Neural precursor cells - embryonic stem cells – mice - improvement
in without producing tumour
(F.H.Moghaddam et al:2009)
Cosmetic surgery
Mesenchymal autologous adipose stem cells - Baldness, facial
lipoatrophy, cosmetic breast augmentation, Wound healing .
(K.Yoshimura etal;2008)

18. Cardiac diseases
Autologous bone marrow SCs - 2.9 % increase in Left ventricular
ejection fraction – reduced damaged area of myocardium
(Martin-Rendon etal:2008)
Osteogenesis imperfecta
Allogeneic mesenchymal cells - 6 children - improvement without
any toxicity except an urticaria
(E.M.Horwitz et. al;2002)
Chronic wounds
Bone Marrow derived autologous stem cells locally on wound.
(E.V. Badiavas;2003)
Kidney and liver disease
Adult human Parietal Epithelial Multipotent Progenitors from
kidney - in mice - improvement of renal function
(Sagrinati etal:2006)

19. Cardiac diseases
Mesenchymal stem cell - Canine chronic ischemia – increased
vascularity and improved cardiac function
(G.V. Silva etal,2004)
Human Mesenchymal SCs – Canine complete heart block –
improved cardiac function (A.N. Plotnikov et al:2007)
Wound healing
Bone Marrow derived autologous stem cell - to treat chronic
ulcer in heifer (J. Das et al:2012)

20. Musculoskeletal diseases
Mesenchymal SCs - osteoarthritis of coxo-femoral joints in dog
(L.L.Black et al:2007)
Mesenchymal stem cell therapy for equine tendinopathy
(R.K.W.Smith:2008)
Bone marrow stem cells in a caprine – osteoarthritis
(J.M.Murphy et al:2003)
Nervous system diseases
Bone marrow mononuclear cells embedded in polymer scaffold-
functional recovery of spinal cord injury
(J B William et. Al. 2011)
Spermatogonial stem cell transplantation

21. J. B. William et. al, TANUVAS, 2011
Functional recovery after intralesional transplantation of autologous
BM SCs embedded in Polymer Scaffold
Pre-operative Grade IV Paraplegia Myelogram: 12th vertebral compression

22. J. B. William et. al, TANUVAS, 2011
Functional recovery after intralesional transplantation of autologous
BM SCs embedded in Polymer Scaffold
C-Arm image of Bone Marrow Harvesting intra-operative image showing exposed
spinal cord after hemilaminectomy

23. J. B. William et. al, TANUVAS, 2011
Functional recovery after intralesional transplantation of autologous
BM SCs embedded in Polymer Scaffold
Post-operative Day 53 Post-operative Day 98:

24. Experimental uses:
Biomedical models for pharmaceutical research
Preclinical evaluation of stem cell for humans
Conservation of endangered species
Stem cell banking
Clinical uses:
Organ replacement therapy and cosmetic uses
Treatment of musculoskeletal and nerve injuries
Assisted reproduction: spermatogonial stem cells
Degenerative diseases

25. a) Favours neoplastic growth
Boy treated with allogenic human fetal neural SCs diagnosed
with a multifocal brain tumor after four years
(N. Amariglio et. al. 2009)
b) Teratoma Formation
Embryonic stem cells – Parkinson’s disease - teratoma
(Sonntag et al. 2006 )
c) Graft-versus-host disease
Immunosuppressive therapy: chance of diseases
d) Ectopic grafting: Grafting in the non target sites

26. a) Adult stem cells: difficult to isolate, short storage life in
culture
b) Embryonic stem cells: difficult to control growth, ethical
issues
c) Donor-to-recipient transmission of pathogens
d) Unwanted differentiation;
Encapsulated structures in infracted areas of heart in mice
(M.Breitbach et. al., 2007)
f) Lack of standardised protocols for culture and therapy

27. a) Autograft or isograft: less chance of rejection
b) Use of polymer scaffolds and use of stem cells at the point of
injury
c) Use of multipotent stem cells, undergone prolonged invitro
differentiation for a specific injury
d) While characterization of differentiated cells immunogenicity to
be checked
e) Commercial production of allogenic adult stem cell lines and
standardized protocols for therapy

28. Stem cell
Bank

29.  Started phase 1 clinical trial of hESC on Jan,2009
 Spinal cord injury repair
 Discontinued on late 2011, for focusing on cancer research
 Oct 2013, Biotime inc. purchased IPR of clinical trials

30. Stempeutics:
Malasian co.
Osteoarthritis
Critical Limb Ischemia
Myocardial ischaemia
Mesenchymal stem cell
Phase II clinical trial

31. a) Institute for Stem Cell Biology and Regenerative Medicine
(inStem), Bangalore (Under DBT)
b) Nichi-In Centre for Regenerative Medicine (NICRM)
Collaborator of university of Torronto, Japan
“Functional Recovery of Spinal Cord Injury Following Application
of Intra lesional Bone Marrow Mononuclear Cells Embedded in
Polymer Scaffold”
First veterinary clinical case report from India
J B William et. al. @ Madras Veterinary college, TANUVAS

32.  National Guidelines for Stem Cell Research , ICMR – DBT, 2013
 National Apex Committee for Stem Cell Research and Therapy
(NAC-SCRT) will monitor activities at national level
 Institutional Committee for Stem Cell Research (IC-SCR) and
Institutional Ethics Committee (IEC) at institutional level
 Invitro SC culture and invivo in experimental animal except
primates permitted: ICSCR and IAC
 Excludes research with animal stem cells - restricted to animal to
animal studies

33.  Human clinical trials require approval of DCGI
(CDSCO) - registered with Clinical Trials Registry of
India (ICMR)
 New human ES cell line can be established after
consent from donor
 Import/export of stem cells necessary by the NAC-
SCRT
No stem cell therapy, other than the hematopoietic
stem cell transplantation (HSCT) for haematological
disorders, is legally allowed

34. Preparation of zygote for ES cell line restricted
 Prohibited human reproductive cloning
 Breeding of animals in which human stem cells have
been introduced prohibited
 Any clinical research on Xenogenic-Human hybrids is
prohibited
Prohibited areas of
research….

35.  Vision 2030 (released on june, 2011)
Stem cell therapy
Generation of stem cell lines
Stem cell for livestock production
Spermatogonial stem cell research

36. Division of physiology and climatology
Mesenchymal stem cells
Embryonic stem cells
Induced pluripotent stem cells
Neural stem cell
Division of Surgery
Bone marrow derived mesenchymal cell
spinal cord and bone injuries
Delayed wound healing in diabetis mellitus
IVRI ERS, Kolkata
Embryonic stem cell cloning

37.  Ethical issues: abortion, human cloning, bioterrorism

38.  Uncontrolled, nonrandomized biased research findings
 Huge funding for the development of stem cell lines
 Fabricated research claims
 Profit motive research programmes by drug companies
 Illegal treatment and internet based scams

40. Future
medicine
Therapy