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