Stem cells as a therapeutic target for diabetes

Abstract

The rapidly increasing number of diabetes patients across the world poses a great challenge to the current therapeutic approach. The traditional method of exogenous supply of insulin has ephemeral effect and often causes lethal hypoglycemia that demands to develop a novel strategy. Recent investigations on regeneration of insulin producing cells (IPCs) revealed that in addition to primary source i.e., pancreatic beta cells, IPCs can be derived from several alternative sources including embryonic, adult, mesenchymal and hematopoietic stem cells via the process of proliferation, dedifferentiation, neogenesis, nuclear reprogramming and transdifferentiation. There is considerable success in insulin independency of diabetes patient after transplantation of whole pancreas and/or the islet cells. However, the major challenge for regenerative therapy is to obtain a large source of islet/beta cells donor. Recent advances in the directed differentiation of stem cells generated a promising hope for a better and permanent insulin independency for diabetes. In this review we discussed stem cells as a potential future therapeutic target for the treatment of diabetes and associated diseases.

Figure 1

A Schematic overview of cell lineage determination during pancreas development. The pancreas has two distinctly different tissues. It is composed of exocrine tissue and endocrine tissues. The exocrine tissue is made up of acinar cells that secrete pancreatic enzymes delivered to the intestine to facilitate the digestion of food. Scattered throughout the exocrine tissue are many thousands of clusters of endocrine cells known as islets of Langerhans. Within the islet, alpha cells produce glucagon; beta cells, insulin; deltacells, somatostatin; ε-cells produce Ghrelin and γ cells, pancreatic polypeptide. Transcription factors involved in the specification of the various lineages are shown in italic.

Figure 2

Schematic diagram depicting Possible sources of beta-cells for cell replacement therapy. During type 1 and type 2 diabetes condition most of the beta cells are destroyed and no or very low insulin is produced. These conditions are treated and beta cells can be regenerated by several sources. Details are given in the text.

Figure 3

Effects of diabetes on diabetic cardiomyopathy. Diabetes mellitus is associated with multiple physiopathological changes in the heart and other organ system. Diabetic cardiomyopathy results in heart failure that occurred due to defects in growth and survival of cardiac progenitor cells (CPC) or other possible causes such as myocardial fibrosis, abnormal myocardial metabolism, hypertension, and coronary artery disease (CAD). These physiopathological changes in the heart can be corrected by supplying the stem cells that may restore the heart function. Details are provided in the text.