1. STEM CELL
THERAPY

2. Stem Cell
Stem Cells
• Are undifferentiated “master” cell that do not
have a specific function
 Can change to one or several different cell
types (differentiate) under proper conditions
 Can undergo unlimited cell division, self-
renewal.

4. DISCARDED STEM CELLS
Embryonic
Excess IVF embryos.
Fetal
Aborted Fetuses
Adult stem cells
Cord blood
Cord (Wharton’s Jelly)
Placenta
Amnion, Amniotic fluid
Endometrium, Menstrual blood,
Milk Teeth and Wisdom teeth

5. Adult stem cell
• A subset of cells which maintain and repair
the tissues in which they reside.
• They are the attractive candidates for cell
based therapies as:
(i) They do not raise ethical conflicts.
(ii) They offer the scope of auto
transplantation without the problem of
allogenic graft rejection.

6. 08/09/12 Dr. Hariom Yadav

9. Immunological barriers
• Rejection- mediated by class 1 MHC and by
antigen presenting cells harbouring the class
2 MHC antigen.
• Can be overcome by marrow transplantation
to induce immunological control.
• Somatic Cell Nuclear Transfer.

10. MESENCHYMAL STEM CELLS
MESENCHYMAL STEM CELLS
ARE MOST PREFERED STEM
CELLS FOR CLINICAL
APPLICATION

11. No risk of No risk of
rejection – used teratoma Pluripotent
across HLA formation
barrier
Precise
No ethical identificatio
issues n
Benefits of Ease of
Immune mesenchymal isolation
and
privileged
stem cell scale up
Greater Genetic
potency of stability
cultured
expanded Lower cost Homogeneous
product Efficient large
of population and
scale
cell culture high rate of cell
expansion
process division

14. Application in Diabetes

15. Pancreas and Islets
Islet beta cells
Isolated Islets in culture Histology of the pancreas
expressing insulin

16. Possible mechanisms of islet β-cell
birth

17. Cell Death mechanisms
• Apoptosis (Programmed cell death)
• Diabetogenic insults
• Cytotoxicity (Drug induced, virus
induced,autoimmune)
• Glucotoxicity
• Lipotoxicity
• Cytoprotection of beta cells can prevent
diabetes and delay diabetic complications.

18. Beta cell apoptosis

21. Normal mouse Experimental diabetic

23. Characterization of human umbilical
cord mesenchymal stem cells
KI67 / Nuclei SMA / Nuclei Nestin Nuclei DesminNuclei Vimentin
Nuclei
Majority of the cells obtained from the cord showed homogenous mesenchymal
population (stained positive for CD44, 73, 90 and 117). The cells expressed the
mesenchymal markers such as nestin, vimentin, desmin and smooth muscle
actin. Oct4, an embryonic stem cells marker was also found to be expressed in
these cord derived MSCs.

24. Islet neogenesis from cord MSCs
Day 10 DTZ positive ILC
Day 0 Day 2
Nucleus/Glucagon/Insulin
Cord MSCs migrate to form Islet like Clusters (ILCs) upon exposure to Serum Free
Medium (SFM) supplemented with growth factors involved in pancreatic
development.
The ILCs are positive for DTZ staining and exhibit immunopositivity for pancreatic
hormones viz; insulin and glucagon.

25. Placenta derived stem cells

26. Generation of Islet-like Cells Aggregates
from DPSCs

29. In vitro charecterizationn of ILSCs

30. Transplanted MSCs & ILCs

34. Indications
• New-onset insulin-dependent diabetes mellitus;
• Diabetes mellitus complicated by diabetic glomerulosclerosis,
chronic renal failure (grade 1 and 2) and anemic syndrome;
• Labile course of diabetes mellitus;
• Diabetes mellitus associated with infections and immune
deficiency;
• Presence of resistantance to treatment trophic ulcers of the
soft tissues;
• Secondary sulfanilamide resistance

35. Diabetic Cardiomyopathy

36. Peripheral Neuropathy

37. Diabetic Nephropathy
• Injected MSCs engraft in damaged kidneys,
differentiate into renal cells, and regulate the
immune response resulting in an efficient treatment
of diabetic nephropathy .
• Additionally, the small percentage of hMSCs in the
transplanted kidneys differentiated into endothelial
cells as evidenced by de novo expression of CD31
• MSCs are able to reconstitute necrotic segments of
diabetic kidneys

38. Wound Healing
• Systemic (I.V) and local administration of bone
marrow-derived MSCs significantly
 increased collagen levels followed by increased
wound-breaking strength I
 moderate (TGF-β, KGF) or significant (EGF, PDGF,
and VEGF) increase.
 neovascularization and formation of inflammation
infiltrate, containing predominantly mononuclear
cells, without tissue necrosis
 formed sweat or sebaceous gland-like structures of
the skin.

39. Diabetic foot
• Infusions of stem cells intra-arterially and I.M
in each foot possibly avoids the need for
amputation.
• Stem cell injection supposedly results in 70-80
percent improvement in pus and wounds

41. Limitations of MSCs
• Poor engraftment and limited differentiation
under in vivo conditions
• The frequency of spontaneous differentiation
of MSCs in the host tissue is extremely rare
• Additional limitation is the potential of MSCs
to differentiate into unwanted mesenchymal
lineages
• Possible malignant transformation and
cytogenetic aberrations of MSCs.

42. Conclusion
• Because of their immunomodulatory ability,
self-renewal, and differentiation capacity,
MSCs are expected to become promising
therapeutic agents for improvement of
diabetes, it’s complications like DCM,
nephropathy, DPN, and wounds in diabetic
patients.