2. Stem CellStem 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. 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.
5. 08/09/12 Dr. Hariom Yadav
6. 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.
7. MESENCHYMAL STEM CELLS MESENCHYMAL STEM CELLS ARE MOST PREFERED STEM CELLS FOR CLINICAL APPLICATION
8. No risk of No risk of rejection – used teratoma Pluripotent across HLA formation barrier PreciseNo ethical identificatioissues n Benefits of Ease ofImmune mesenchymal isolation andprivileged stem cell scale upGreater Geneticpotency of stabilityculturedexpanded Lower cost Homogeneousproduct Efficient large of population and scale cell culture high rate of cell expansion process division
9. Application in Diabetes
10. Pancreas and IsletsIslet beta cells Isolated Islets in culture Histology of the pancreasexpressing insulin
11. Possible mechanisms of islet β-cell birth
12. 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.
13. Beta cell apoptosis
14. Normal mouse Experimental diabetic
15. Characterization of human umbilical cord mesenchymal stem cellsKI67 / Nuclei SMA / Nuclei Nestin Nuclei DesminNuclei Vimentin NucleiMajority of the cells obtained from the cord showed homogenous mesenchymalpopulation (stained positive for CD44, 73, 90 and 117). The cells expressed themesenchymal markers such as nestin, vimentin, desmin and smooth muscleactin. Oct4, an embryonic stem cells marker was also found to be expressed inthese cord derived MSCs.
16. Islet neogenesis from cord MSCs Day 10 DTZ positive ILC Day 0 Day 2 Nucleus/Glucagon/InsulinCord MSCs migrate to form Islet like Clusters (ILCs) upon exposure to Serum FreeMedium (SFM) supplemented with growth factors involved in pancreaticdevelopment.The ILCs are positive for DTZ staining and exhibit immunopositivity for pancreatichormones viz; insulin and glucagon.
17. Placenta derived stem cells
18. Generation of Islet-like Cells Aggregates from DPSCs
19. In vitro charecterizationn of ILSCs
20. Transplanted MSCs & ILCs
21. 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
22. Diabetic Cardiomyopathy
23. Peripheral Neuropathy
24. 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
25. 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.
26. 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
27. 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.
28. 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.