Currently, there does not exist a strategy that can reduce diabetes and scientists are working towards a cure and innovative approaches by employing stem cell-based therapies. research. production of insulin-secreting cells was also achieved by the directed differentiation of iPSCs using small molecules and growth factors in the culture. The primary advantages of employing iPSCs are that they do not present ethical concerns and only pose a low risk of teratoma formations. However, the reprogramming of somatic cells into iPSCs achieved with the aid of viral transfection of transcription factors requires the use of genomes. These genomes are harmful as they can trigger mutations and hamper the normal function of iPSCs and their ability to differentiate, in addition to causing the formation of tumors. Mesenchymal stem cells: The method for isolating mesenchymal stem cells (MSCs) from the rat bone marrow was first described by Friedenstein as explained in previous Rabbit Polyclonal to Cytochrome c Oxidase 7A2 studies. Although the bone marrow is the richest source of MSCs[27-29], they have also been successfully isolated from adipose tissues[30,31], fetal liver, umbilical cord and its blood[33,34], fibroblasts, endometrium, placenta, trabecular and compact bone. MSCs have been found to be able to differentiate into mesodermal, endodermal and ectodermal cells under suitable culture conditions. MSCs are suitable for the regeneration of tissues, as they do not result in teratoma formation. Other advantages of using MSCs for stem cell-based therapy include the ease of isolation, expansion to large quantities and their multipotential differentiation capacity. In addition, their ability to circumvent immune recognition and inhibit immune responses also makes them ideal candidates for immunomodulatory cell therapy in immune-mediated diseases. According to studies performed by Xu et al, the direct injection of MSCs into the pancreas had helped alleviate diabetes symptoms by improving the metabolic control in animal models, counteracting autoimmunity, enhancing islet engraftment and survival, besides serving as a source of growth factors and cytokines. Direct injection of MSCs has not only been found to be effective in improving the functions of the pancreas but also healed related symptoms like diabetic foot and neuropathy. The main limitation posed by MSCs is their potential to differentiate into unwanted mesenchymal lineages, which can be detrimental to their therapeutic applications. SA-4503 The possibility of malignant transformations and cytogenetic aberrations of MSCs may also considered drawbacks. Results of some MSCs clinical trials in T1DM are shown in Table ?Table11[45-51]. Table 1 Results of some mesenchymal stem cells clinical trials in diabetes mellitus type 1 into functioning -cellsNormalization of chronic hyperglycemia in a diabetic ratHuman placenta SA-4503 ?derived MSCsDifferentiated into islet-like cell clusters and transplanted into streptozocin-induced diabetic miceRestoration of normoglycemia in diabetic miceHuman umbilical cord blood derived MSCsDifferentiated into IPC through intravenous administrationImprovement in glycemic profiles, histological improvement of insulatesWharton’s jelly and amniotic membrane derived MSCs(1) Differentiated into IPC and transplanted into the liver; (2) Infected with gene and differentiated to IPC; and (3) Differentiated into IPC and transplanted into the liver of STZ-induced diabetic ratsExpression of insulin Secretion of C-peptide; expression of pancreas-specific genes; correspondence to high concentrations of glucose; reduction of blood glucose levels after 4 wk of transplantation Open in a separate window MSCs: Mesenchymal stem cells; IPC: Insulin-producing cells. Human embryonic stem cells (hESCs): hESCs are characterized by properties such as pluripotency of gene expression, self-renewal ability, and high proliferative capacity[52,53] thereby making them a valuable treatment option in all types of medicine. Numerous and differentiation strategies have been SA-4503 adopted for the production of functional pancreatic islets. Generally, hESCs are initially harvested from the inner cell mass of the blastula post fertilization when the cells are still capable of differentiation into all types of germ layers and there is a high level of telomerase activity. This is followed by the differentiation of the hESCs into definitive endoderm, which further undergo differentiation into functional -cells, through a chain of endodermal intermediates[54,55]. These techniques cause the hESCs to be exposed to specific transcription factors that can facilitate coordinated activation and inhibit intracellular signaling pathways. Although cell signaling and epigenetic factors involved in the differentiation process remain to be studied.