Diabetes mellitus is an endocrine disorder and chronic disease associated with significant morbidity and mortality. More than 415 million people are affected by this disorder worldwide. Over the past decade, numerous hypoglycaemic agents have emerged but are able to perfectly control blood glucose. Stem-cell therapy is used to generate surrogate beta cells or for islet transplantation in diabetic patients. It will open the possibility of alleviating the many debilitating complications associated with hypoglycaemic agents including glucagon-like peptide (GLP-1) mimetics, dipeptidyl-peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT2) inhibitors. Stem cell transplantation is best suited for those patients who are unable to control diabetes mellitus even with exogenous insulin injection. Curative therapy for diabetes using islet transplantation has been successful to some extent, however, a shortage of donor organs, graft rejection, and the need for continued immune suppression shifted the attention towards alternative means of producing beta cells from islet expansion. Potential sources of stem cells therapy in diabetes are-
- Xenogenic islet cells
- Cadaver derived human islet cells
- Engineered IPCs (insulin-producing cells)
- Embryonic stem cells
- Bone-marrow derived stem cells
- Umbilical cord-derived stem cells
Xenogenic islets from pig donors have appeared as an alternative to islets from human donors for pancreatic islet transplantation. Microencapsulation of pig islets can be used for practical treatment for insulin-dependent diabetes mellitus. Pancreatic differentiation of embryonic stem cells derived from the embryo can be induced by retinoic acid which plays an important role in pancreatic development. Human-induced pluripotent stem cells are generated by reprogramming human somatic cells, thus having self-renewal ability and can be used for deriving glucose-responsive β-like cells. Progenitor cells have received increasing attention as they directly drift towards the injured pancreas where they quickly differentiate into insulin-producing cells, thus decreasing the glucose levels towards normoglycemia. Adult stem cells have regeneration property and they play a significant role in maintaining and repairing local tissue. Bone-marrow-derived stem cells have the property to transdifferentiate into the classical embryonic germ cell and are potential cells for diabetes therapy. They can differentiate into beta-cells in the diabetic pancreas without causing immune rejection in the recipient. Mesenchymal stem cell therapy is being extensively investigated in both animal models and clinical trials. Mesenchymal stem cells (MSCs) are evaluated as the most remarkable cell source because of their immunomodulatory and tissue regenerative properties including self-renewal capability, pluripotency, low antigenicity, reduced toxicity, and expansion in vitro to obtain sufficient cells for treatment. These cells were utilized for their differentiation into insulin-secreting pancreatic beta cells and are derived from bone marrow, adipose tissue, amniotic fluid, umbilical cord blood, and placenta. MSCs demonstrate improved engraftment of pancreatic islets through the suppression of inflammatory damage and provide a supportive micro-environmental niche making them ideal candidates when a fully matched donor is not available. Bone marrow-derived and umbilical cord-derived MSCs have an extreme possibility of transformed into insulin-producing cells.
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