Stem Cells in the Treatment of Insulin-Dependent Diabetes Mellitus

Abstract

Diabetes affects over 350 million people worldwide, with the figure projected to rise to nearly 500 million over the next 20 years, according to the World Health Organization. Insulin-dependent diabetes mellitus (type 1 diabetes) is an endocrine disorder caused by an autoimmune reaction that destroys insulin-producing β-cells in the pancreas, which leads to insulin deficiency. Administration of exogenous insulin remains at the moment the treatment mainstay. This approach helps to regulate blood glucose levels and significantly increases the life expectancy of patients. However, type 1 diabetes is accompanied by long-term complications associated with the systemic nature of the disease and metabolic abnormalities having a profound impact on health. Of greater impact would be a therapeutic approach which would overcome these limitations by better control of blood glucose levels and prevention of acute and chronic complications. The current efforts in the field of regenerative medicine are aimed at finding such an approach. In this review, we discuss the time-honored technique of donor islets of Langerhans transplantation. We also focus on the use of pluripotent stem and committed cells and cellular reprogramming. The molecular mechanisms of pancreatic differentiation are highlighted. Much attention is devoted to the methods of grafts delivery and to the materials used during its creation.

Keywords: cellular therapy; diabetes; differentiation; gene expression; pancreas.

Fig. 1

Schematic representation of endocrine cell fate specification during pancreatic development. A) An uncommitted endocrine progenitor cell can become an α-cell or transform into a second progenitor cell with the β- or δ-cell lineage fates expressing Arx and Pax4. B) A change in the cell fate decision is caused by the lack of Pax4; C) A change in the cell fate decision is caused by the lack of Arx; D) A change in the cell fate decision is caused by the lack of Pax4 and Arx [By 18]

Fig. 2

Schematic overview of decellularization-recellularization technology. A) The intact organ contains cellular components (red ellipses) and ECM (blue network), as well as growth factors (green dots); B) An acellular organ scaffold after complete removal of cellular elements; C) The organ scaffold after recellularization with autologous cells (yellow ellipses) [By 199]