stem cell therapy
DESCRIPTION
TRANSCRIPT
STEM CELL THERAPY
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.
Stem Cell
EmbryonicExcess IVF embryos.
FetalAborted Fetuses
Adult stem cellsCord bloodCord (Wharton’s Jelly)PlacentaAmnion, Amniotic fluidEndometrium, Menstrual blood,Milk Teeth and Wisdom teeth
DISCARDED STEM CELLS
• 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.
Adult stem cell
04/10/23 Dr. Hariom Yadav
• 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.
Immunological barriers
MESENCHYMAL STEM CELLS
MESENCHYMAL STEM CELLSARE MOST PREFERED STEMCELLS FOR CLINICALAPPLICATION
Benefits of mesenchymal
stem cell
No risk ofrejection – usedacross HLAbarrier
No risk ofteratomaformation
Pluripotent
No ethicalissues
Immuneprivileged
Greaterpotency ofculturedexpandedproduct
Lower cost ofcell cultureprocess
Efficient largescaleexpansion
Homogeneouspopulation andhigh rate of celldivision
Preciseidentification
Ease ofisolation andscale up
Geneticstability
Application in Diabetes
Pancreas and Islets
Islet beta cellsexpressing insulin Isolated Islets in culture Histology of the pancreas
Possible mechanisms of islet β-cell birth
• 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.
Cell Death mechanisms
Beta cell apoptosis
Normal mouse Experimental diabetic
KI67 / Nuclei SMA / Nuclei Nestin Nuclei DesminNuclei VimentinNuclei
Majority 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.
Characterization of human umbilicalcord mesenchymal stem cells
Day 0 Day 2 Day 10 DTZ positive ILC
Nucleus/Glucagon/Insulin
Cord MSCs migrate to form Islet like Clusters (ILCs) upon exposure to Serum FreeMedium (SFM) supplemented with growth factors involved in pancreatic development.The ILCs are positive for DTZ staining and exhibit immunopositivity for pancreatichormones viz; insulin and glucagon.
Islet neogenesis from cord MSCs
Placenta derived stem cells
Generation of Islet-like Cells Aggregates from DPSCs
In vitro charecterizationn of ILSCs
Transplanted MSCs & ILCs
• 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
Indications
Diabetic Cardiomyopathy
Peripheral Neuropathy
• 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
Diabetic Nephropathy
• 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.
Wound Healing
• 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
Diabetic foot
• 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.
Limitations of MSCs
• 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.
Conclusion