Insulin - producing cells derived from stem cells: recent progress and future directions

Abstract

Type 1 diabetes is characterized by the selective destruction of pancreatic β-cells caused by an autoimmune attack. Type 2 diabetes is a more complex pathology which, in addition to β-cell loss caused by apoptotic programs, includes β-cell dedifferentiation and peripheric insulin resistance. β-Cells are responsible for insulin production, storage and secretion in accordance to the demanding concentrations of glucose and fatty acids. The absence of insulin results in death and therefore diabetic patients require daily injections of the hormone for survival. However, they cannot avoid the appearance of secondary complications affecting the peripheral nerves as well as the eyes, kidneys and cardiovascular system. These afflictions are caused by the fact that external insulin injection does not mimic the tight control that pancreaticderived insulin secretion exerts on the body's glycemia. Restoration of damaged β-cells by transplantation from exogenous sources or by endocrine pancreas regeneration would be ideal therapeutic options. In this context, stem cells of both embryonic and adult origin (including β-cell/islet progenitors) offer some interesting alternatives, taking into

Beta cell coupling and connexin expression change during the functional maturation of rat pancreatic islets

“…As young islets reach full secretory maturation, their beta cells show CX36 coupling like that of adult beta cells. The close parallelism between these events and the close relationship between Cx36 and insulin levels raises the possibility that CX36 may be a useful target for inducing the maturation of beta cells in vitro [45], and for new approaches to the therapy of neonatal diabetes [46,47]. In both islet types, the extent of ethidium bromide transfer was greater than that of LY, consistent with the presence of CX36 but not CX43 channels.…”

Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin-producing cells in vivo and reduce hyperglycemia in diabetic mice

“…Insulin-dependent diabetes mellitus (IDDM) is characterized by the rapid development of potentially severe metabolic abnormalities caused by insulin deficiency (Gepts, 1965, Notkins and Lernmark, 2001, Herold et al, 2005, Keymeulen et al, 2005, Santana et al, 2006, Voltarelli et al, 2007. IDDM results from deficient insulin secretion due to destruction of beta cells in the islets of Langerhans in the pancreas.…”

Present Accomplishments and Future Prospects of Cell-Based Therapies for Type 1 Diabetes Mellitus

“…The tissue-specific differentiation of ESCs, pancreas-derived multipotent progenitor/stem cells, extrapancreatic adult stem cells (bone-marrow (BM) derived stem cells, neural progenitor cells, umbilical cord blood (UCB)-derived stem cells, etc.) or induced pluripotent stem cells (iPSCs) established from adult differentiated cells, into unprecedented quantities of cells with an insulin expressing phenotype in vitro has tremendous potential in -cells replacement therapy (Aguayo-Mazzucato & Bonner-Weir, 2010;Furth etal., 2009;Guo et al, 2009;Santana et al, 2006;Sordi et al, 2008;Stanley et al, 2008;Tang 2004). Additionally, the immunosuppressive, anti-inflammatory properties of stem cells shared among ESCs and several types of non-haematopoietic stem cells (HSCs) such as BM-derived mesenchymal stem cells (BM-MSCs) and UCB-derived stem cells are an added advantage.…”