Stem Cells: Potential for Therapy
hpadh@yahoo.com
NIPERD
Replacement parts
needed for
transplantation or
tissue reconstruction
Tissue
Engineering
Replacement parts
needed for
transplantation or
tissue reconstruction
Tissue
Engineering
Stem cells are potentially immortal cells capable
of self-renewal and also give rise to differentiated
cells
No area of research since gene therapy has
evoked so much enthusiasm and hope

Stem cells are body ‘master cells’

Differ from mature cells which are fully committed
Stem
cells are thus reserve supply of replacement
cells that multiply when needed
Formed at conception & gradually become
specialized

Our body retains stem cell reserves in various
organs to replace diseased tissue

As the stem cell reserve gets depleted, we
succumb to diseases, disorders and process of
aging


Longer life span, almost ‘immortal’

High degree of plasticity – Pluripotent

Easier to isolate and cultivate

Limitless supply of cells in culture

More genetic stability

Ethical issues

Form teratomas

Will face immune rejection
Thomson et al
Science, 1998



Fischbachand FischbachJ. Clin. Inv. 114:1364
Self-renewal: can
divide indefinitely
Can undergo
asymmetric division
Retain the capacity to
develop into any adult
cell type
Oct-4 (Pou-Transcription
factor)
Stage Specific Embryonic
Antigens
SSEA-3
SSEA-4
Tumor Recognition
Antigens
TRA-1-60
TRA-1-81
High Alkaline Phosphatase
activity
High Telomerase Activity
Karyotyping

Diabetes 1

Neurodegenerative
disorders

Myocardial infarction

Spinal cord injury

Severe liver damage

Haematological disorders

Severe eye and ear damage
watch.htm
Homoeostasis
Within a cell
Between cells/tissue
In an organism
Balance of Cell Supply
Figure: Measurement of ROS in SKO- and SKOM- infected MEF
compared to empty vector. D indicates day hereafter

Maintain capacity for self-renewal

Undergo asymmetric division or development

Differentiate to limited subset of cell types
Hematopoietic
Fetal liver & spleen, bone marrow, peripheral
blood, umbilical cord blood
Liver
Portal zone near bile duct
Intestine
Crypts
Epidermal
Basal layer of skin
Limbal stem cells
Pigmented ciliary margin
Breast Epithelium
Cap cells and basal layer of mammary gland
Pancreas
Islets and ducts
Mesenchymal
Bone marrow stroma, adipose tissue
Tooth & Ear
Placenta
Germline stem cells
Testis, Ovary (?)
Cancers
Acute and Chronic Leukemia
High-Risk Solid Tumors
Hodgkin & Non-Hodgkin Lymphoma
Myelodysplastic Syndrome
Blood Disorders
Beta Thalassemia
Diamond-Blackfan Anemia , Fanconi Anemia, Severe Aplastic Anemia
Sickle Cell Disease
Immune Disorders
Chronic Granulomatous Disease
Hystiocytic Disorders
Leukocyte Adhesion Deficiency
Severe Combined Immunodeficiency Diseases
Wiskott-Aldrich Syndrome
Metabolic Disorders
Krabbe Disease
Hurler Syndrome
Metachromatic Leukodystrophy
Sanfilippo Syndrome
Cord Blood Registry, www.cordblood.com
iPS cells are a type of pluripotent stem cell from an adult somatic cell,
by inducing a "forced" expression of certain genes.
iPS cells believed to be identical to natural pluripotent stem cells, such
as embryonic stem cell in many respects, such as
• the expression of certain stem cell genes and proteins,
• chromatin methylation patterns,
• embryoid body formation,
• teratomas formation,
• viable chimera formation,
• potency and,
• differentiability.
A Brief History of iPS Findings
2006
2007
2007
2008
2007
SOX2
This intron less gene encodes a member of the SRY-related HMG-box (SOX)
family of transcription factors involved in the regulation of embryonic development
and in the determination of cell fate.
MYC
The protein encoded by this gene is a multifunctional, nuclear phosphoprotein that
plays a role in cell cycle progression, apoptosis and cellular transformation. It
functions as a transcription factor that regulates transcription of specific target
genes. Mutations, overexpression, rearrangement and translocation of this gene
have been associated with a variety of hematopoietic tumors
KLF4 Kruppel-like factor 4
Klf4 functions upstream of Nanog in ES cell self-renewal and in preventing ES cell
differentiation. Klf4 interacts directly with Oct4 and Sox2 when expressed at levels
sufficient to induce induced pluripotent stem cells
OCT4 (POU class 5 homeobox 1)
This gene encodes a transcription factor containing a POU homeodomain. This
transcription factor plays a role in embryonic development, especially during early
embryogenesis, and it is necessary for embryonic stem cell pluripotency
• New tools for studying development
• Development of disease models
• Novel cell-based therapies
Patient specific iPS lines could
overcome problem of immune
rejection
• Avoid most ethical considerations
associated with hES cells iPS
Fischbachand Fischbach, J. Clin. Inv. 114:1364
FIRST STEM CELL CLINICAL TRIAL APPROVED BY FDA

Food and Drug Administration (FDA) had approved the
first-ever clinical trial of stem cell therapy on human
subjects, in 2009.

The trial, funded by the biotech company Geron, was
to test a procedure to repair spinal cord damage.
 The therapy involves the injection of precursor cells
into the spine, where the cells will then differentiate into
oligodendrocytes, the cells type that sheathes and protects
the nerves of the spinal cord.
Adult Stem Cell Research Network, www.ascrnetwork.com
Trounston et al. BMC Medicine 2011, 9: 52
Trounston et al. BMC Medicine 2011, 9: 52
Trounston et al. BMC Medicine 2011, 9: 52
Trounston et al. BMC Medicine 2011, 9: 52
Stem cell clinical trials in India- Present status
Study
Condition
Intervention
Status
Safety and efficacy of autologous
bone marrow stem cells in patients
with spinal cord injury
Spinal cord
injury
Autologous
bone marrow
derived stem
cells
Recruiting
Mesenchymal stem cells in critical
limb ischemia
Critical limb
ischemia
Mesenchymal
stem cells;
Plasmalyte A
Active, not
recruiting
Clinical trial to study the efficacy and
safety of different doses of bone
marrow derived mesenchymal stem
cells in patients with critical limb
ischemia due to Buergers disease
Critical limb
ischemia;
Buerger’s
disease
Allogenic
mesenchymal
stem cells;
Standard
protocol of care
Not yet
recruiting
Ex vivo cultured bone marrow
derived allogenic MSCs in AMI
Myocardial
infarction
Stem cells;
Plasmalyte A
Active, not
recruiting
Allogenic mesenchymal stem cells
in osteoarthritis
Osteoarthriti
s of knee
Ex-vivo cultured Recruiting
adult allogenic
MSCs;
Plasmalyte A
www.clinicaltrials.gov
Study
Condition
Intervention
Status
Safety and efficacy of autologous
bone marrow stem cells for treating
osteoarthritis
Osteoarthritis
Autologous
bone marrow
stem cells
Enrolling
by
invitation
Autologous mesenchymal stem cell
transplant for Parkinson’s disease
Parkinson’s
disease
Autologous
bone marrow
derived stem
cells
Active, not
recruiting
Safety and efficacy of autologous
bone marrow stem cells for treating
chronic renal failure
Chronic
renal failure
Autologpus
bone marrow
stem cells
Recruiting
Efficacy of autologous bone marrow
derived stem cell transplantation in
patients with type 2 Diabetes
Mellitus
Type 2
Diabetes
Mellitus
Stem cell
harvest;
Angiographic
transplantation
of stem cells
Unknown
Evaluation of the role of
mesenchymal stem cells in the
treatment of graft versus host
disease
Graft vs Host Mesenchymal
disease
stem cell
infusion
Unknown
www.clinicaltrials.gov
Study
Condition
Intervention
Status
Unknown
Efficacy of autologous bone marrow
derived stem cell transplantation in
patients with Type 2 Diabetes
Mellitus-2
Type 2
Diabetes
Mellitus
Stem cell
transplantation
Clinical trial on diabetic foot using
peripheral blood derived stem cells
for treating critical limb ischemia
Diabetic foot;
critical limb
ischemia; leg
ulcers
Will receive GUnknown
CSF and
peripheral blood
derived
mononuclear
cells; G-CSF;
Standard
therapy
Safety and efficacy of autologous
bone marrow stem cells in treating
spinal cord injury
Spinal cord
injuries
Laminectomy;
Intrathecal
Completed
Pilot study of efficacy of
Lactobacillus CD2 Lozenges in
preventing high-dose chemotherapy
induced oral mucositis in patients
undergoing hematopoietic stem cell
transplantation
Oral
mucositis
Lactobacillus
CD2 lozenges
Recruiting
www.clinicaltrials.gov
Study
Condition
Intervention
Status
Study of the monoclonal
antibody CT-011 in diffuse large
B-Cell lymphoma following
autologous stem cell
transplantation
CT-011
Lymphoma, Large
cell, diffuse;
Lymphoma, Mixed
cell, diffuse; Primary
Mediastinal Large Bcell lymphoma;
Transformed
follicular lymphoma;
Relapsed
Completed
BMAC enhanced coronary
artery bypass grafting (CABG)
Congestive heart
failure
Recruiting
Harvest
SmartPReP
2 BMAC
system
www.clinicaltrials.gov
Study
Condition
Intervention
Status
Safety and efficacy of autologous
bone marrow mononuclear cells in
patients with severe critical limb
ischemia
Critical limb
ischemia
Autologous
bone marrow
mononuclear
cells
Recruiting
Granulocyte colony stimulating
factor (G-CSF) in acute liver failure
and alcoholic hepatitis
Liver failure,
acute
Grnaulocyte
colony
stimulating
factor
Recruiting
G-CSF and erythropoetin in survival Chronic liver
of patients with decompensated liver disease
disease
G-CSF+EPO;
Placebo
Recruiting
Efficacy of granulocyte colonystimulating factor and erythropoetin
for patients with acute-on-chronic
liver failure
Granulocyte
colony
stimulating
factor (G-CSF)
and
Erythropoeitin
(EPO); Placebo
Recruiting
Acute on
chronic
hepatic
failure
www.clinicaltrials.gov
Study
Condition
Intervention
Status
Feasibility study of autologous bone
marrow aspirate concentrate for
treatment of CLI
Arterial
occlusive
diseases
SmartPReP2
BMAC system
Active, not
recruiting
Safety and efficacy evaluation of two
year imatinib treatment in adjuvant
gastrointestinal stromal tumor (GIST)
Gastrointesti
nal stromal
tumors
Imatinib
mesylate
Active, not
recruiting
Study of NTx-265: Human
Chorionic Gonadotropin (hCG) and
Epoetin Alfa (EPO) in acute ischemic
stroke patients
Stroke
Human
chorionic
gonadotropin
(hCG), epoetin
alfa (EPO);
Saline Placebo
Terminated
, Has
results
REGENESIS (CA): A study of NTxTM265: Human Chorionic Gonadotropin
(hCG) and Epoetin Alfa (EPO) in
acute ischemic stroke patients
Stroke
NTxTM-265;
rhCG, rEPO;
Saline placebo
Terminated
www.clinicaltrials.gov
Study
Chemotherapy in treating
patients with acute
lymphoblastic leukemia and
diffuse non-hodgkin’ s
lymphoma
Condition
Leukemia;
Lymphoma
Intervention
Status
Asparaginase;
Unknown
cyclophosphamide;
cytarabine;
daunorubicin
hydrochloride;
doxorubicin
hydrochloride;
etoposide;
ifosfamide;
mercaptopurine;
methotrexate;
prednisone;
vincristine sulfate;
conventional surgery;
radiation therapy
www.clinicaltrials.gov
hpadh@yahoo.com