Stem cell therapy involves three main concepts: direct injection of stem cells into damaged tissues, transplantation of differentiated cells derived from stem cells, and stimulation of endogenous stem cells to facilitate repair. Sources of stem cells for tissue repair include embryonic stem cells, induced pluripotent stem cells, umbilical cord blood stem cells, and somatic stem cells. Stem cell therapy is being studied as a potential treatment for various diseases and injuries, including heart disease, diabetes, neurological disorders, liver disease, and blood disorders. However, challenges remain regarding immune rejection, control of differentiation, and ethical issues with some stem cell sources.

1. STEM CELL THERAPY

3.  Damage to an organ initiates a series of
events that lead to the reconstruction of
the damaged tissue, including
proliferation, differentiation, and
migration of various cell types; release of
cytokines and chemokines; and
remodeling of the extracellular matrix.
 Endogenous stem and progenitor cells
are among the cell populations that are
involved in these injury responses.

5.  Injection directly into the damaged organ
or systemically
 Transplantation of differentiated cells
derived from stem cells.
 Stimulation of endogenous stem cells to
facilitate repair (erythropoietin,
granulocyte colony-stimulating factor,
and granulocyte-macrophage colony-
stimulating factor )
Three different therapeutic
concepts

7. SOURCES OF STEM CELLS
FOR TISSUE REPAIR
 Embryonic stem (ES) cells,
 Induced pluripotent stem (iPS) cells,
 Umbilical-cord blood stem cells
(USCs)
 somatic stem cells

8. Embryonic Stem Cells
 Could generate almost limitless
numbers of cells.
 Source:-unused human blastocysts
from fertility clinics.
 Human ES cells are difficult to culture
and grow slowly.
 Ethically controversial

9. Induced Pluripotent Stem
Cells
 Adult somatic cells can be converted
(“reprogrammed”) into pluripotent cells.
 Potential advantages--somatic cells from
patients would generate pluripotent cells
genetically identical to those of the
patient.
 These cells are not subject to the same
ethical constraints as ES cells.

11. Umbilical-Cord Stem Cells
 less graft-versus-host disease
 less human leukocyte antigen
restriction than adult marrow stem
cells
 less likely to be contaminated with
herpesvirus
 it is unclear how many different cell
types can be generated from USCs

12. Cont…
 Methods for differentiating these cells
into non-hematopoietic phenotypes
are largely lacking.
 Nevertheless, there are ongoing
clinical trials of these including
cirrhosis, cardiomyopathies, multiple
sclerosis, burns, stroke, autism, and
critical limb ischemia.

13. Organ-Specific Multipotent
Stem Cells
 Cells potentially could be obtained from the
patient and amplified in cell culture,
circumventing the problems associated with
immune rejection.
 Relatively easy to harvest from some tissues,
such as bone marrow and blood, but are
difficult to harvest from other tissues, such as
heart and brain.
 Sources:- Bone marrow MSCs, CD34+
HSCs, cardiac mesenchymal cells, and
adipose-derived stem cells (ASCs)

14. Pluripotent stem cells
ESCs iPSCs
Tissue stem cells
(multipotent)
Source Embryo Somatic cell
Adult, juvenile and
fetal organs
Rate of proliferation High High Usually low
Availability High High Low
Spontaneous
differentiation
Yes Yes No
Capacity to produce
diverse cell types
High High Low

15. DISEASE-SPECIFIC
APPLICATIONS OF STEM
CELLS

16. Ischemic Heart Disease and
Cardiomyocyte Regeneration
 A small but measurable improvement in
cardiac function and, in some cases,
reduction in infarct size.
 Transplantation of bone marrow-derived
stem cells improved outcome for patients
in heart failure
 The beneficial clinical impact reflects an
indirect effect of the transplanted cells
rather than cell replacement

18. Diabetes
 Pancreas is digested with collagenase
that frees islets from surrounding cells
 Centrifugation of isolates containing
mainly alpha and beta cells
 And transplanted through a catheter
into the liver where they become
permanantly established.

20. Nervous System
 Clinical trials:-Multiple sclerosis,
epilepsy, Alzheimer’s disease, ALS,
acute and chronic stroke, numerous
genetic disorders, traumatic brain
injury, Parkinson’s disease, and others

21. Parkinson’s disease

22. Spinal Cord Injury

23. Liver
 ES cells can be differentiated into
hepatocytes and transplanted in
animal models of liver failure without
the formation of teratomas.
 Clinical trials are in progress in
cirrhosis with numerous cell types,
including MSCs, USCs, HSCs, and
ASCs.

24. Hematopoietic Cell
Transplantation
 Remarkable regenerative capacity
 Ability to home to the marrow space
following intravenous
injection(CXCL12, also known as
stromal cell–derived factor 1 & and the
alpha-chemokine receptor CXCR4 )
 Ability of the stem cell to be
cryopreserved

25. CATEGORIES OF HCT
 Allogeneic transplantation
 Autologous transplantation

26. Allogeneic transplantation
 Not genetically identical.
 Risk of graft-versus-host disease
(GVHD)
 Degree of matching between donor
and recipient for human leukocyte
antigen (HLA) defines risk of
complications

27.  The genes of major relevance to
transplantation include HLA-A, -B, -C,
and –D.
 With standard techniques, the risk of
graft rejection is 1–3%, and the risk of
severe, life-threatening acute GVHD is
~15% following transplantation
between HLA-identical siblings.

28. Autologous transplantation
 Removal and storage of the patient’s
own stem cells with subsequent
reinfusion after the patient receives high-
dose myeloablative therapy.
 No risk of GVHD or graft rejection with
autologous transplantation
 Site--posterior and anterior iliac crests
 1.5 to 5 × 10^8 nucleated marrow cells
per kilogram are collected

29. THE TRANSPLANT
PREPARATIVE REGIMEN
 To eradicate the patient’s underlying
disease and, in the setting of allogeneic
transplantation,
 To immunosuppress the patient
adequately to prevent rejection of the
transplanted marrow.
 Depends on the disease setting and
source of marrow(e.g severe combined
immunodeficiency,aplastic anemia )

30. Cont…
 High activity against the tumor in
question at conventional doses
 Myelosuppression as their predominant
dose-limiting toxicity
 Busulfan, cyclophosphamide,
melphalan, thiotepa, carmustine,
etoposide, and total-body irradiation in
various combinations

31.  THE TRANSPLANT PROCEDURE
 ENGRAFTMENT AND IMMUNE
RECONSTITUTION

33. COMPLICATIONS
FOLLOWING
HEMATOPOIETIC CELL
TRANSPLANT

35. Graft-versus-Host Disease
 Acute GVHD --within the first 3
months
 Chronic GVHD--between 3 months
and 2 years

36. Acute GVHD
 Grade I acute GVHD--little clinical significance
 Grades II to IV GVHD are associated with
significant symptoms and a poorer probability of
survival, and require aggressive therapy

37. Cont…
 Treatment:--
 Calcinuerin inhibitor (cyclosporine or
tacrolimus) combined with an
Antimetabolite (methotrexate or
mycophenolate mofetil) following
transplantation.
Anti T-cell immune globulin (ATG)
Prednisone at a daily dose of 1–2
mg/kg.

38. Chronic GVHD
 Resembles an autoimmune disorder with
malar rash, sicca syndrome, arthritis,
obliterative bronchiolitis, and bile duct
degeneration and cholestasis
 Susceptible to significant
infection(prophylactic trimethoprim-
sulfamethoxazole)

39. Infection

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