This document describes a case study of a 37-year-old woman with spinal cord injury who received a transplant of multipotent stem cells derived from human umbilical cord blood. Within 41 days of the transplant, the patient showed improved sensory perception and mobility in her hips and thighs. CT and MRI scans also showed regeneration of the spinal cord at the injury site and some regeneration of the cauda equina below. The results suggest that umbilical cord blood multipotent stem cell transplantation may be an effective treatment for spinal cord injury patients.
Human amniotic fluid cells (hAFCs) may differentiate into multiple cell lineages and thus have a great potential to become a donor cell source for regenerative medicine. The ability of hAFCs to differentiate into germ cell and oocyte-like cells has been previously documented. Herein we report the potential use of hAFCs to help restore follicles in clinical condition involving premature ovarian failure.
Cartilage Repair using Stem cell & OrthobiologicsVaibhav Bagaria
Regenerating Cartilage is a challenge. What's new in this field of cartilage regeneration and the current status of the stem cell use in this field is described.
There are a lot of orthopedic conditions and injuries that presently have limited treatment options available.
Here regenerative technologies comes up as a ray of hope among surgeons for the treatment by functionally repairing the tissues and organs using growth factors, stem cells and products developed by genetic engineering with the advancement in the stem cells research field .
The purpose of this presentation is to first provide idea about the orthopedic conditions along with the therapeutic potential of stem cells to treat these diseases.
Human amniotic fluid cells (hAFCs) may differentiate into multiple cell lineages and thus have a great potential to become a donor cell source for regenerative medicine. The ability of hAFCs to differentiate into germ cell and oocyte-like cells has been previously documented. Herein we report the potential use of hAFCs to help restore follicles in clinical condition involving premature ovarian failure.
Cartilage Repair using Stem cell & OrthobiologicsVaibhav Bagaria
Regenerating Cartilage is a challenge. What's new in this field of cartilage regeneration and the current status of the stem cell use in this field is described.
There are a lot of orthopedic conditions and injuries that presently have limited treatment options available.
Here regenerative technologies comes up as a ray of hope among surgeons for the treatment by functionally repairing the tissues and organs using growth factors, stem cells and products developed by genetic engineering with the advancement in the stem cells research field .
The purpose of this presentation is to first provide idea about the orthopedic conditions along with the therapeutic potential of stem cells to treat these diseases.
Pluripotent Stem Cells and their applications in disease modelling, drug disc...tara singh rawat
This ppt gives an insight of the potential and possibilities of pluripotent stem cells research in disease modelling, drug discovery and regenerative medicine
Ortho: to make straight or right. The use of biologic substances to prompt, stimulate or support a “healing event” within the body.The use of biologic substances to promote healing or reduce pain.The use of platelets and stem cells in treatment and management of musculoskeletal conditions
Induced Pluripotent Stem Cell & Cell Dedifferentiation: The Breakthrough of S...Vincentsia Vienna
The phenomenon of cell dedifferentiation is yet one promising trend to explore. In future, the science fiction of regenerative medicine could be turned into reality.
A Brief History of Regenerative MedicineJohn Makohen
In the presentation ISREGEN outlines the history of regenerative medicine fro it's earliest days when Robert Briggs and Thomas King began cloning frogs to the present medicinal advancements in stem cell research and repair.
Stem cells in regenerative biology and medicinePasteur_Tunis
Présentation réalisée par Shahragim Tajbakhsh durant le cours du réseau international des instituts Pasteur de "Médecine Génomique: du diagnostic à la thérapie " (17-21 octobre 2016)
Pluripotent Stem Cells and their applications in disease modelling, drug disc...tara singh rawat
This ppt gives an insight of the potential and possibilities of pluripotent stem cells research in disease modelling, drug discovery and regenerative medicine
Ortho: to make straight or right. The use of biologic substances to prompt, stimulate or support a “healing event” within the body.The use of biologic substances to promote healing or reduce pain.The use of platelets and stem cells in treatment and management of musculoskeletal conditions
Induced Pluripotent Stem Cell & Cell Dedifferentiation: The Breakthrough of S...Vincentsia Vienna
The phenomenon of cell dedifferentiation is yet one promising trend to explore. In future, the science fiction of regenerative medicine could be turned into reality.
A Brief History of Regenerative MedicineJohn Makohen
In the presentation ISREGEN outlines the history of regenerative medicine fro it's earliest days when Robert Briggs and Thomas King began cloning frogs to the present medicinal advancements in stem cell research and repair.
Stem cells in regenerative biology and medicinePasteur_Tunis
Présentation réalisée par Shahragim Tajbakhsh durant le cours du réseau international des instituts Pasteur de "Médecine Génomique: du diagnostic à la thérapie " (17-21 octobre 2016)
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Stem-cell therapy in medicine–how far we came and what we can expect?Apollo Hospitals
The name ‘stem-cell’ is making the news in recent times both for good and not. The current articles tries to give a snap shot of the scientific and clinical picture of stem-cells in medicine as of today and discuss what it have to offer in the to the mankind. The article discusses the characters and types of stem-cells, their current indication in therapeutics (both established and upcoming), as well as their use in research. It also gives a brief overview of the current laws guiding its use in clinical practice and the various cultural beliefs associated with the use of same.
Rotator cuff repair using a stem cell approachZakary Bondy
This presentation communicates current methods for rotator cuff repair mainly focusing on mesenchymal and tendon-derived stem cells. It looks to expand on future research in this field by communicating a future experiment to expand on current knowledge of tendon-derived stem cells.
Reprogramming to pluripotency is possible from adult cells of different tissues and species through the ectopic expression of defined factors. The generated induced Pluripotent Stem Cells (iPSCs) are relevant for various purposes, including disease modeling, drug or toxicity screening and autologous cell therapy. Over the last few years, increased efforts are being made to improve the reprogramming techniques, the efficiency and quality of the generated iPSCs, as well as to identify the best cell source to be reprogrammed. Cells derived from fetal tissues, such as amniotic fluid, placenta and umbilical cord, offer distinct advantages in terms of reprogramming compared to adult somatic cells. Importantly, fetal cells are more primitive, easily achievable in sufficient numbers and are devoid of any ethical concern. They show great plasticity, high proliferation rate, low immunogenity and absence of teratoma formation. Therefore, they can be reprogrammed much faster and more efficiently than adult cells. Here, we provide a comprehensive overview of the advantages of reprogramming fetal sources in comparison to other commonly used cell types.
Advance Access publication 29 January, 2004
Establishment of human embryonic stem cell lines from
frozen±thawed blastocysts using STO cell feeder layers
Se-Pill Park
1,4, Young Jae Lee
1
, Keum Sil Lee
1
, Hyun Ah Shin
1
, Hwang Yoon Cho
1
,
Kil Saeng Chung
2
, Eun Young Kim
1,4 and Jin Ho Lim
3
1
Maria Infertility Hospital Medical Institute/Maria Biotech, Seoul 130-812,
2
Department of Animal Sciences, Kon-Kuk University,
Seoul 143-701 and
3
Maria Infertility Hospital, Seoul 130-812, Korea
4
To whom correspondence should be addressed at Maria Infertility Hospital Medical Institute, 103-11, Sinseol-dong,
Dongdaemun-gu, Seoul, 130-812 Korea. E-mail: [email protected] or [email protected]
S.-P.Park and E.Y.Kim contributed equally to this work
BACKGROUND: Recently, human embryonic stem (hES) cells have become very important resources for basic
research on cell replacement therapy and other medical applications. The purpose of this study was to test whether
pluripotent hES cell lines could be successfully derived from frozen±thawed embryos that were destined to be dis-
carded after 5 years in a routine human IVF-embryo transfer programme and whether an STO cell feeder layer
can be used for the culture of hES cells. METHODS: Donated frozen embryos (blastocysts or pronuclear) were
thawed, and recovered or in vitro developed blastocysts were immunosurgically treated. All inner cell masses were
cultured continuously on an STO cell feeder layer and then presumed hES cell colonies were characterized.
RESULTS: Seven and two cell lines were established from frozen±thawed blastocysts (7/20, 35.0%) and pronuclear
stage embryos (2/20, 10.0%), respectively. The doubling time of hES cells on the immortal STO cell feeder layer was
~36 h, similar to that of cells grown using fresh mouse embryonic ®broblast (MEF) feeder conditions. Subcultured
hES cell colonies showed strong positive immunostaining for alkaline phosphatase, stage-speci®c embryonic antigen-
4 (SSEA-4) and tumour rejection antigen 1-60 (TRA1-60) cell surface markers. Also, the hES colonies retained nor-
mal karyotypes and Oct-4 expression in prolonged subculture. When in vitro differentiation of hES cells was
induced by retinoic acid, three embryonic germ layer cells were identi®ed by RT±PCR or indirect immunocyto-
chemistry. CONCLUSIONS: This study indicates that establishment of hES cells from frozen±thawed blastocysts
minimizes the ethical problem associated with the use of human embryos in research and that the STO cell feeder
layer can be used for the culture of hES cells.
Key words: embryonic stem cells/frozen±thawed human blastocysts/inner cell mass/in vitro differentiation /STO cell
Introduction
Embryonic stem (ES) cells are derived from the inner cell mass
(ICM) cells of early mammalian blastocyst. These cells are
pluripotent and generally retain their long-term proliferative
potential in an undifferentiated state. Also, ES cells can
differentiate into d.
Novel Way to Isolate Adipose Derive Mesenchymal Stem Cells & Its Future Clini...IOSR Journals
Abstract: Adipose-derived stem cells (ADSCs), were isolated from discarded human fat tissue, obtained from csection with our recently modified methods, in Stem Cell & Regenerative Medicine Lab, VSBT. Here we develop
two methods to isolate Adipose derived mesenchymal stem cells with enzyme digestion and use of
phosphatidylcholine and deoxycholate. Surface protein expression was analyzed by flow cytometry to
characterize the cell phenotype. The multi-lineage potential of ADSCs was testified by differentiating cells with
adipogenic inducer. ADSCs can be cultured in vitro for up to one month without passage. Also, the flow
cytometry analysis showed that ADSCs expressed high levels of stem cell related surface marker CD105.
ADSCs have strong proliferation ability, maintain their phenotypes, and have stronger multi-differentiation
potential. The molecular basis of ADSC differentiation was studied using bioinformatics tools with an aim to
identify the key proteins involved in differentiation, such that they could be used as potential targets for drug
development for the treatment of obesity. The key proteins involved were found to be PPARG and C/EBPα. The
structures of the proteins were retrieved from MMDB (Molecular Modelling Database) and PDB (Protein Data
Bank) respectively. Key Words: Adipose-derived stem cells, Mesenchymal stem cells, Enzyme digestion, Phosphatidylcholine, Deoxycholate, PPARG, C/EBPα, etc.
thGAP - BAbyss in Moderno!! Transgenic Human Germline Alternatives ProjectMarc Dusseiller Dusjagr
thGAP - Transgenic Human Germline Alternatives Project, presents an evening of input lectures, discussions and a performative workshop on artistic interventions for future scenarios of human genetic and inheritable modifications.
To begin our lecturers, Marc Dusseiller aka "dusjagr" and Rodrigo Martin Iglesias, will give an overview of their transdisciplinary practices, including the history of hackteria, a global network for sharing knowledge to involve artists in hands-on and Do-It-With-Others (DIWO) working with the lifesciences, and reflections on future scenarios from the 8-bit computer games of the 80ies to current real-world endeavous of genetically modifiying the human species.
We will then follow up with discussions and hands-on experiments on working with embryos, ovums, gametes, genetic materials from code to slime, in a creative and playful workshop setup, where all paticipant can collaborate on artistic interventions into the germline of a post-human future.
Explore the multifaceted world of Muntadher Saleh, an Iraqi polymath renowned for his expertise in visual art, writing, design, and pharmacy. This SlideShare delves into his innovative contributions across various disciplines, showcasing his unique ability to blend traditional themes with modern aesthetics. Learn about his impactful artworks, thought-provoking literary pieces, and his vision as a Neo-Pop artist dedicated to raising awareness about Iraq's cultural heritage. Discover why Muntadher Saleh is celebrated as "The Last Polymath" and how his multidisciplinary talents continue to inspire and influence.
2137ad - Characters that live in Merindol and are at the center of main storiesluforfor
Kurgan is a russian expatriate that is secretly in love with Sonia Contado. Henry is a british soldier that took refuge in Merindol Colony in 2137ad. He is the lover of Sonia Contado.
The perfect Sundabet Slot mudah menang Promo new member Animated PDF for your conversation. Discover and Share the best GIFs on Tenor
Admin Ramah Cantik Aktif 24 Jam Nonstop siap melayani pemain member Sundabet login via apk sundabet rtp daftar slot gacor daftar
2137ad Merindol Colony Interiors where refugee try to build a seemengly norm...luforfor
This are the interiors of the Merindol Colony in 2137ad after the Climate Change Collapse and the Apocalipse Wars. Merindol is a small Colony in the Italian Alps where there are around 4000 humans. The Colony values mainly around meritocracy and selection by effort.
The Legacy of Breton In A New Age by Master Terrance LindallBBaez1
Brave Destiny 2003 for the Future for Technocratic Surrealmageddon Destiny for Andre Breton Legacy in Agenda 21 Technocratic Great Reset for Prison Planet Earth Galactica! The Prophecy of the Surreal Blasphemous Desires from the Paradise Lost Governments!
1. A 37-year-old spinal cord-injured female patient,
transplanted of multipotent stem cells from human
UC blood, with improved sensory perception and
mobility, both functionally and morphologically:
a case study
K-S Kang1
, SW Kim2
, YH Oh3
, JW Yu4
, K-Y Kim4
, HK Park5
, C-H Song4
and
H Han2
1
Laboratory of Stem Cell and Tumor Biology, College of Veterinary Medicine, Seoul National University, Seoul, Korea, 2
Seoul Cord Blood Bank,
Histostem Co., Seoul, Korea, 3
New Life Clinic, Seoul, Korea, 4
Chosun University Hospital, Kwang-ju, Korea, and 5
Department of Surgery, College of
Medicine, Hanyang University, Seoul, Korea
HLA-matched UC blood-derived multipotent stem cells were directly
transplanted into the injured spinal cord site of a 37-year-old female
patient suffering from spinal cord injury (SPI). In this case, human
cord blood (UCB)-derived multipotent stem cells improved sensory
perception and movement in the SPI patient’s hips and thighs within
41 days of cell transplantation. CT and MRI results also showed
regeneration of the spinal cord at the injured site and some of the cauda
equina below it. Therefore, it is suggested that UCB multipotent stem
cell transplantation could be a good treatment method for SPI patients.
Keywords
clinical trial, multipotent stem cells, spinal cord injury, UC blood.
Introduction
Spinal cord injury (SPI) is a major medical problem world-
wide. Great efforts have been made to improve the
condition of SPI patients, not only regarding sensory
perception but also functional ability [1]. There are some
recent reports related to animal model experiments that
indicate some hope for SPI patients [2,3].
The blood remaining in the UC following birth contains
hematopoietic precursors, which represent an important
alternative source for transplantation for hematopoietic
diseases [4Á/6]. However, controversy exists as to whether
such blood also contains multipotent stem cells (MSC) that
are capable of differentiating into cells of different
connective tissue lineages, such as bone, cartilage and
adipose tissues. Stem cells are the best candidates for tissue
engineering of musculoskeletal tissues [7Á/9]. To date, the
most common source of MSC has been BM, but aspirating
BM from a patient is an invasive procedure. In addition, it
has been demonstrated that the number and differentiating
potential of BM-derived MSC decrease with age [10].
Therefore, the search for alternative sources of MSC is of
significant value. So far, little success has been reported
regarding the isolation, characterization and differentiation
of MSC from umbilical cord blood (UCB). Erices et al. [11]
reported that UCB-derived mononuclear cells gave rise to
two adherent cell types, one of which expressed MSC
related to surface Ag. Mareschi et al. [12] reported that, in
given conditions, it was possible to isolate MSC from BM
but not from UCB. However, Goodwin et al. and our
laboratory [13,14] have recently reported cells that have
multilineage differentiation activity, isolated from UCB,
and express bone, fat and neural markers. Kakinuma et al.
[15] reported that UCB-derived MSC could differentiate
into hepatic progenitor cells. However, none of these
reports provided sufficient evidence to fulfill the qualify-
ing criteria for MSC, because relatively heterogeneous
cells were reported by the groups. It has been reported that
MSC from BM can improve SPI functional models in the
Correspondence to: Hoon Han, MD PhD, Seoul Life Foundation, Bldg. 518-4 Dunchon-Dong Kang Dong Ku, Seoul 134-060, Korea.
Cytotherapy (2005) Vol. 7, No. 4, 368Á/373
– 2005 ISCT DOI: 10.1080/14653240500238160
2. laboratory [3]. However, there has been no report of cord
blood MSC related to SPI. This study is the first report
regarding a clinical trial for a chronic SPI patient using
MSC derived from UCB. In this study, we report that MSC
from UCB can show functional and morphologic improve-
ment in a chronic SPI patient.
Methods
Human UCB harvest and preparation of MSC
Human UCB samples were harvested (Seoul Cord Blood
Bank, Seoul, Korea) from term and pre-term deliveries at
the time of birth with the mothers’ consent. Blood samples
were processed within 24 h of collection. The mono-
nuclear cells were separated from UCB using Ficoll-
PaqueTM
PLUS (Amersham Bioscience, Uppsala, Sweden)
and were suspended in culture medium (DEME; Gibco,
Grand Island, NY, USA) containing 15% FBS, 100 U/mL
penicillin,100 mg/mL streptomycin, 2 mM L-glutamine
and 1 mM sodium pyruvate. The cells were then seeded at
a density of 1)/106
cells/cm2
in culture flasks. After 7 days
of culture, suspended cells were removed and adherent
cells were additionally cultured (Figure 1). Cells were
maintained at 378C in a humidified atmosphere containing
5% carbon dioxide, with a change of culture medium
every 3Á/4 days. Approximately 50Á/60% of confluent cells
was detached with 0.1% trypsin-EDTA and replated at a
density of 2)/103
cells/cm2
in culture flasks.
Patients and cell transplantation
A 37-year-old female who fell into a ditch in July 1985
underwent an emergency operation, approved by the
Korean Food and Drug Administration, to repair the SPI
derived from a compression fracture of the 12th thoracic
vertebra and fracture dislocation of the 11thÁ/12th thoracic
vertebrae. She eventually became paraplegic and was
dependent on the use of an electromotive wheel chair
for her movement for 19 years and 6 months before
treatment with MSC.
The patient was admitted to Chosun University Hospi-
tal, Kwang-ju, Korea, for UCB-derived MSC therapy via
the Department of Neurosurgery in 2004. Her vital signs
were within the normal range, her motor power of upper
extremities was 4/5 and of lower extremities 0/5 on a
manual muscle test. The range of motion of joint was
absent and grade I spasticity was noticed on lower
extremities using the Ashworth’s scale. On sensoryÁ/neural
examination, the dermatome of the 9th thoracic vertebra
was normal in range but one of the 10thÁ/12th thoracic
vertebrae was decreased on the left side. The dermatome
up to the 11th thoracic vertebra was normal in range, one
of the 12th thoracic vertebra was decreased, and one below
the 1st lumbar vertebra was absent in right side. Deep
tendon reflex of both knees and ankles was decreased.
Perianal sensitivity and voluntary anal sphincter contrac-
ture were not observed. The extent of neural injury
according to the standard of the ASIA (American Spinal
Injury Association) was complete paraplegia of the 10th
thoracic vertebra.
An open procedure (posterior approach with laminect-
omy) was performed under general anesthesia to ensure
proper stem cell administration. After observation of the
injured dura of the spinal cord at the level of the 10thÁ/
12th thoracic vertebrae, 1 mL (1)/106
cells) of cord blood
multipotent stem cells was injected into the subarachnoid
space of the most distal part of the normal spinal cord.
Then an additional 2 mL (one million) stem cells was
injected diffusely into the intradural and extradural space
of the injured spinal cord. Hemovac was not inserted for
the purpose of implanted stem cell protection. Before and
after treatment, no immunosuppressive drugs were used.
Neural differentiation of multipotent stem cells
in vitro
Cells were plated at 1000Á/2000 cells/cm2
in complete
medium with the addition of 10 ng/mL basic fibroblast
growth factor (bFGF; Roche, Indianapolis, IN, USA
Switzerland), 10 ng/mL human epidermal growth factor
(hEGF; Roche) and 10 ng/mL human neural growth factor
(hNGF; Invitrogen, Grand Island, NY, USA) for 14 days.
Figure 1. The morphology of multipotent stem cells from human UCB.
The morphology is fibroblastic and spindle-shaped.
Transplantation of multipotent stem cells from human UC blood 369
3. We have reported previously that our MSC have been seen
to differentiate into neuronal cells, in vitro, by immuno-
fluorescent assay, RT-PCR and Western blot analysis [14].
In this study, to confirm the neural differentiation ability
again, the expression of neural related Ag was examined.
Rabbit polyclonal Ab were used against NSE (Chemicon,
Temecula, CA, USA) and GFAP (Chemicon). For im-
munocytochemical NSE and GFAP labeling, cells were
rinsed with PBS and fixed with 3.7% formaldehyde in PBS
for 10 min at room temperature. They were then treated
with ice-cold 100% methanol for 10 min, 100% acetone
for 5 min and 0.4% Triton X-100 in PBS for 10 min, with
triple PBS rinses between treatments. Samples were treated
with 2% horse serum (Gibco-BRL, Gaithersburg, MD,
USA) and 2% goat serum (Zymed Laboratories Inc., San
Francisco, CA, USA) in PBS containing 4% BSA (PBS/
BSA) for 100 min at 378C to block non-specific binding of
primary Ab. Ab were diluted in PBS/BSA plus 2% horse
and 2% goat sera at 1:200 for NSE and 1 : 200 for GFAP.
The primary Ab were incubated on cells for 1 h at 378C.
Samples were rinsed three times with PBS. Fluorescent
secondary Ab were added concurrently: FITC, TRITC
anti-rabbit (Zymed Laboratories Inc.) diluted 1 : 200 in
PBS/BSA plus 2% horse and 2% goat sera, for 45 min at
378C. Slides were rinsed with PBS and mounted in
Gelvatol (Lab Vision, Fremont, CA, USA). Fluorescence
was visualized using a fluorescent microscope.
Flow cytometric analysis of cord-derived
multipotent stem cells
To detect surface Ag, cells were detached and washed with
PBS (Jeil Biotechserveices Inc., Daegu, Korea) and
incubated at 48C for 30 min with the following cell-
specific Ab conjugated with FITC or PE (Becton Dick-
inson, San Jose, CA, USA): SH2 (CD105, endoflin), SH3
(CD73), CD13, CD29 (b1 intergrin), CD44, CD49e (a5
intergrin), CD54 (ICAM-1), CD90 (Thy-1), CD14, CD34,
CD45, CD31, CD49d (a4 intergrin), CD106 (VCAM-1),
HLA-ABC and HLA-DR.
Results
In order to assess their ability to differentiate into neuronal
cells, cord blood-derived MSC were cultured in neuro-
genic medium. When exposed to hEGF/hFGF/hNGF for
2 weeks, UCB-derived MSC could express neural-specific
Ag and showed some morphologic features of neural cells,
such as long multi-polar extensions and branching ends.
After neuronal differentiation, the UCB-derived MSC
expressed NSE and GFAP, which are cytoskeletal proteins
in neurons and astrocytes, respectively. Therefore, MSC in
human UCB can expand in vitro and differentiate into
non-mesenchymal cells, as we previously reported [14].
Before using the isolated MSC, we confirmed cell
viability by trypan blue exclusion and counted cells from
primary cultured MSC using a hemocytometer. We used
only populations with /95% viable cells (the total viable
cell number, 1)/106
) for the transplantation. The isolated
MSC are shown in Figure 1. The morphology was
fibroblastoid and spindle-shaped. Flow cytometric analysis
revealed that the cells were negative for CD24 (B cells),
CD62L (B cells, T cells, monocytes, NK cells), CD62P
(platelets, megakaryocytes) and CD20 (B cells). UCB-
derived cells were found to be positive for CD29
(leukocytes), CD44 (hyaluronidase receptor), CD14 (mye-
lomonocytic cells), CD49b (a2 intergrin) and CD135
(multipotent precursors).
Before the operation, electrodiagnostic results had
shown that the somatosensory and motor-evoked poten-
tials of both tibial nerves revealed no response. A nerve
conduction study of the common peroneal and tibial
nerves also showed no response. The dermatomal soma-
tosensory-evoked potential showed no response below
the right 12th thoracic and left 11th thoracic vertebra
(Table 1), and no somatosensory and motor-evoked
potential below the right 10th and left 9th thoracic
vertebra (Table 2). For radiologic findings, thoracolumbar
plain films, myelogram and MRI revealed the old
compression fracture of the 12th thoracic vertebra and
posterior dislocation of the 11th vertebra, and the resultant
SPI by compression at the 10thÁ/12th thoracic vertebrae
level (Figure 2e).
The patient could move her hips and feet her hip skin
on day 15 after transplantation. On day 25 after transplan-
tation, her feet responded to stimulation. On post-
operative day (POD) 7, motor activity was noticed and
improved gradually in her lumbar paravertebral and hip
muscles. She could maintain an upright position by herself
on POD 13. From POD 15 she began to elevate both lower
legs about 1 cm, and hip flexor muscle activity gradually
improved until POD 41. The posterior tibial nerve
conduction, which was not observed pre-operatively,
showed 100 mV amplitude, 55.3 m/s conduction velocity
on POD 20. This conduction improved up to 300 mV
amplitude, 56.3 m/s on POD 27.
370 K-S Kang et al.
4. Examinations were carried out for somatosensory and
motor-evoked potentials. The potentials were activated
down to L1 in the right leg and to T12 in the left leg,
compared with T10 of the right leg and T9 of the left leg
before transplantation. The timeÁ/course of these poten-
tials was also examined. It became clear that the somato-
sensory and motor-evoked potentials had gone down to L2
in both legs (Table 2). Regarding the dermatomal
somatosensory-evoked potential, we also examined the
patient in a timeÁ/course manner. These results also
showed that the dermatomal somatosensory-evoked po-
tential was recovered to L2 in both legs on day 41 after
operation compared with pre-operation (T12 in the right
leg, T11 in the left leg; Table 1). These results suggested
that the sensory and motor nerves of the patient might
have been continuously improved and regenerated.
To prove regeneration of the spinal cord, CT and MRI
scans were performed of the thoracolumbar spine. These
results revealed that there was a compression fracture in
T12 with retropulsion of the fragment into the spinal
canal. Anterior subluxation of T11 on T12 caused a
compression effect of the spinal cord before transplanta-
tion. The atrophied spinal cord was expanded after stem
cell administration, with total laminectomy, and the low-
ermost portion of the atrophied spinal cord was enlarged,
along with thinning and interruption of the calcified pia
mater at the T12Á/L1 level on pre-contrast axial CT films
(Figure 2b, d). Sagittal T2 weighted SE MRI revealed
regenerating spinal cord at the injured level (Figure 2f,
arrow) and some of the cauda equina below it (Figure 2f,
arrow heads).
Discussion
Although the presence of multipotent MSC/progenitor
cells in cord blood is widely reported [9,11,16,17], these
cells are known to proliferate poorly in the in vitro culture
system. There has been skepticism regarding the presence
of human multipotent stem/progenitor cells in UCB
[12,18]. Despite the fact that BM represents the main
available source of MSC, the use of BM-derived cell is not
always acceptable because of the high degree of viral
infection and significant drop in the number of the cells
and proliferation/differentiation capacity with age.
Houghton et al. [19] reported BM-derived stem cells as a
potential source of gastric cancer. However, it has not yet
been reported that UCB-derived cells can form tumor.
Therefore, UCB-derived MSC have many advantages
because of:
Table 2. Change of somatosensory and motor-evoked potentials after transplantation
Date 10/11 11/1 11/8 11/15
R L R L R L R L
T9 14.3 14.5 13.9 13.7 14.0 13.7 14.2 14.5
T10 19.5 NE 17.6 18.8 15.8 16.3 16.5 16.1
T11 NE NE 19.0 19.4 17.0 17.6 18.1 17.9
T12 NE NE 19.8 20.0 17.6 18.0 18.3 18.7
L1 NE NE 20.0 NE 18.5 18.8 19.5 19.0
L2 NE NE NE NE NE NE NE NE
NE, no effect; R, right leg; L, left leg.
Table 1. Changes of dermatomal somatosensory-evoked potential after transplantation
Date 10/11 10/12 10/26 11/1 11/8 11/15
R L R L R L R L R L R L
T10 31.4 42.2 27.8 36.6 32.0 29.8 42.0 36.8 30.4 36.8 31.2 33.2
T11 34.2 46.8 34.6 37.4 40.2 39.6 44.6 40.8 48.8 39.6 43.8 47.0
T12 50.4 NE 51.2 44.6 49.2 51.6 55.6 53.8 51.6 45.4 64.2 56.8
L1 NE NE 51.4 NE NE 55.8 56.8 64.4 66.0 58.4 72.0 76.8
L2 NE NE NE NE NE NE NE NE 74.8 72.0 NE NE
NE, no effect; R, right leg; L, left leg.
Transplantation of multipotent stem cells from human UC blood 371
5. j the immaturity of newborn cells compared with adult
cells
j the fact that immune reactions causing dysfunctional
grafts can be avoided.
Therefore, we have established a new paradigm for stem
cell therapy without immunosuppression, because cord
blood-derived stem/progenitor cells are less likely to
attack a recipient’s body than BM-derived cells. In this
case report, we have shown that UCB-derived MSC
improved the condition, physically and morphologically,
within 41 days after cell transplantation, of an SPI patient
who had suffered for about 20 years. The specific
mechanisms and reasons regarding how the patient
improved so quickly now remain to be explained fully.
Further studies are urgently needed.
Possible explanations of the effects are:
j UCB-derived MSC are able to produce many cytokines
and growth factors (unpublished data)
j MSC can directly reconstitute injured spinal cord (we
have also demonstrated that cord blood-derived MSC
are capable of differentiating into neural features
in vitro [20]).
These results strongly support the clinical improvement of
the patient. However, as well as these two possible
explanations, we cannot exclude the act of laminectomy,
which can release compressed areas of the spinal cord,
because we have reported on only one case study.
Based on their large ex vivo expansion capacity as well as
on their differentiation potential, cord blood-derived MSC
can be visualized as an attractive source for cellular and
gene transfer therapy for incurable and neurodegenerative
diseases such as Alzheimer’s disease, Parkinson’s disease,
Nieman-Pick disease, diabetes and so on. Furthermore,
UCB provide no ethical problems for basic studies and
clinical application compared with embryonic stem cells.
References
1 Sipski M, Jackson AB, Gomez-Marin O et al. Effects of gender
on neurogenic and functional recovery after spinal cord injury.
Arch Phys Med Rehabil 2004;85:1826Á/36.
2 Myckatyn TM, Mackinnon SE, Mcdonald JW. Stem cell
transplantation and other novel techniques for promoting
recovery from spinal cord injury. Transplant Immunol 2004;12:
343Á/58.
3 Ankeny DP, McTigue DM, Jakeman LB. Bone marrow trans-
plants provide tissue protection and directional guidance for
axon after contusive spinal cord injury in rats. Exp Neurol
2004;190:17Á/31.
4 Broxmeyer HE, Douglas GW, Hangoc G et al. Human umbilical
cord blood as a potential source of transplantable hematopoietic
stem and progenitor cells. Proc Natl Acad Sci USA 1989;86:
3828Á/32.
5 Gluckman E, Broxmeyer HA, Auerbach AD et al. Hematopoietic
reconstitution in a recipient with Fanconi anemia by means of
umbilical cord blood from HLA identical sibling. N Engl J Med
1989;321:1174Á/89.
6 Gluckman E, Rocha V, Boyer-Chammard A et al. Outcome of
cord-blood transplantation from related and unrelated donors.
N Engl J Med 1997;337:373Á/81.
Figure 2. The atrophied spinal cord is expanded after stem
cell administration with total laminectomy on pre-contrast axial CT
films (b). The lowermost portion of the atrophied spinal cord is
enlarged, along with thinning and interruption of the calcified pia
mater at the T12Á/L1 level on pre-contrast axial CT films (d).
Sagittal T2 weighted SE MRI reveal regenerating spinal cord at the
injured level (arrow, f) and some of the cauda equina below it (arrow
heads, f). CT images before cell transplantation (a, c) and MRI image
before cfell transplantation (e).
372 K-S Kang et al.
6. 7 Ohgushi H, Caplan AI. Stem cell technology and bioceramics:
from cell to gene engineering. J Biomed Mater Res 1999;48:
913Á/27.
8 Gang EJ, Jeong JA, Hong SH et al. Skeletal myogenic
differentiation of mesenchymal stem cells isolated from human
umbilical cord blood. Stem Cells 2004;22:617Á/24.
9 Gang EJ, Hong SH, Jeong JA et al. In vitro mesengenic potential
of human umbilical cord blood-derived mesenchymal stem cells.
Biochem Biophys Res Comm 2004;321:102Á/8.
10 D’Ippolito G, Schiller PC, Ricordi C et al. Age-related
osteogenic potential of mesenchymal stromal stem cells from
human vertebral bone marrow. J Bone Miner Res 1999;14:
1115Á/22.
11 Erices A, Conget P, Minguell J. Mesenchymal progenitor cells in
human umbilical cord blood. Br J Haematol 2000;109:235Á/42.
12 Mareschi K, Biasin E, Piacibell W et al. Isolation of human
mesenchymal stem cells: bone marrow versus umbilical cord
blood. Haematologica 2001;86:1099Á/100.
13 Goodwin H, Bicknese A, Chien S et al. Multilineage differentia-
tion activity by cells isolated from umbilical cord blood:
expression of bone, fat, and neural markers. Biol Blood Marrow
Transplant 2001;7:581Á/8.
14 Jeong JA, Gang EJ, Hong SH et al. Rapid neural differentiation
of human cord blood-derived mesenchymal stem cells. Neuro-
Report 2004;15:1731Á/4.
15 Kakinuma S, Tanaka Y, Chinzei R et al. Human umbilical cord
blood as a source of transplantable hepatic progenitor cells. Stem
Cells 2003;21:217Á/27.
16 Lee OK, Kuo TK, Chen WM et al. Isolation of multi-potent
mesenchymal stem cells from umbilical cord blood. Blood
2004;103:1669Á/75.
17 Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for
alternative sources of postnatal human mesenchymal stem cells:
candidate MSC-like cells from umbilical cord. Stem Cells
2003;21:105Á/10.
18 Wexler SA, Donaldson C, Denning-Kendall P et al. Adult bone
marrow is a rich source of human mesenchymal ‘stem’ cells but
umbilical cord and mobilized adult blood are not. Br J Haematol
2003;121:368Á/74.
19 Houghton JM, Stoicov C, Nomura S et al. Gastric cancer
originating form bone marrow-derived cells. Science 2004;
26:1568Á/71.
20 Jeong JA, Gang EJ, Hong SH et al. Rapid neural differentiation
of human cord blood-derived mesenchymal stem cells. Neurore-
port 2004;15:1731Á/4.
Transplantation of multipotent stem cells from human UC blood 373