Development of insulin-producing cells from primitive biologic precursors

Abstract

Purpose of review The differentiation of pluripotent and multipotent stem cells into insulin producing cells has the potential to create a renewable supply of replacement β cells with tremendous utility in the treatment of diabetes. The purpose of this review is to summarize recent advancements in the field, with emphasis on the limitations of this technology as it relates to the β cell. Recent findings Multiple groups have developed successful in vitro protocols to differentiate human embryonic stem cells and selected tissue specific stem cells into progenitors capable of insulin production and glucose-stimulated insulin secretion. The resulting cells are immature β like cells that co-express multiple islet hormones and lack the full complement of genes necessary for normal function. Protocols that include in vivo maturation in immune compromised mice produce cells with a more mature phenotype. Summary Although tremendous progress has been made in differentiating stem cells into insulin producing cells, there is still more research needed to produce a fully functional adult β cell.

Vitamin D and Vitamin A Receptor Expression and the Proliferative Effects of Ligand Activation of These Receptors on the Development of Pancreatic Progenitor Cells Derived from Human Fetal Pancreas

“…Biological research on stem and islet cells has led to the development of experimental islet cell replacement using harvested islets and efforts to solve this problem using islets grown from stem cells therapy [8,9]. The signals necessary for effective promotion of islet beta-cell development must be identified for stem cells therapy to become an effective treatment, or even a cure, for T1DM and a treatment option for type 2 diabetes mellitus (T2DM) [8,9].…”

“…The signals necessary for effective promotion of islet beta-cell development must be identified for stem cells therapy to become an effective treatment, or even a cure, for T1DM and a treatment option for type 2 diabetes mellitus (T2DM) [8,9]. Our laboratory has successfully isolated and characterized a population of fetal pancreatic progenitor cell (PPC) model from first trimester human fetal pancreas using a basic protocol developed for differentiating PPCs into insulin-secreting islet-like cell clusters (ICCs) [10,11].…”

Current Status of Islet Cell Replacement and Regeneration Therapy

“…There have been impressive advances in the derivation of ␤-like cells from human ES cells that provide great hope that such an approach may one day offer a plentiful source of ␤-cells for transplantation (95,96). There continues to be remarkable progress in this field, including the identification of small molecules that promote the differentiation of human ES cells into pancreatic progenitor cells (97).…”

Use of Encapsulated Stem Cells to Overcome the Bottleneck of Cell Availability for Cell Therapy Approaches

“…Moreover, no in vivo experiment with encapsulated pluripotent stem cells have been reported. Nevertheless, in animal studies, often with immunodeficient animals, these cells showed a high therapeutic potential and were used for the treatment of diabetes, spinal cord injury and visual impairment by creation of new insulin-producing cells, neurons and retinal cells, respectively [35][36][37]. Pluripotent stem cells have also been investigated in animal models concerning several diseases such as Parkinson's disease, muscular dystrophy and heart failure [38][39][40].…”