Insulin-producing Surrogate β-cells From Embryonic Stem Cells: Are We There Yet?

Abstract

Embryonic stem cells (ESCs) harbor the potential to generate every cell type of the body by differentiation. The use of hESCs holds great promise for potential cell replacement therapies for degenerative diseases including diabetes mellitus. The recently discovered induced pluripotent stem cells (iPSCs) exhibit immense potential for regenerative medicine as they allow the generation of autologous cells tailored to the patients' immune system. Research for insulin-producing surrogate cells from ESCs has yielded highly controversial results, because many steps and factors in the differentiation process are currently still unknown. Thus, there is no consensus on common standard protocols. The protocols presently used established the differentiation from pluripotent cells toward pancreatic progenitor cells. However, none of the differentiation protocols reported to date have generated by exclusive in vitro differentiation sufficient numbers of insulin-producing cells meeting all essential criteria of a β-cell. The cells often lack the crucial function of regulated insulin secretion upon glucose stimulation. This review focuses on past and current approaches to the generation of insulin-producing cells from pluripotent sources, such as ESCs and iPSCs, and critically discusses the hurdles to be taken before insulin-secreting surrogate cells derived from these stem cells will be of clinical use in humans.

Reconstituting pancreas development from purified progenitor cells reveals genes essential for islet differentiation

“…Current methods using embryonic stem cells or other multipotent cell lines generate polyhormonal cells that require xenotransplantation for months before the emergence of insulin-secreting cells resembling islet β-cells (33). In contrast, our system produced monohormonal cells within 1 wk of culture, including glucose-responsive insulin-secreting cells.…”

Functional evaluation of ES cell-derived endodermal populations reveals differences between Nodal and Activin A-guided differentiation

“…Although significant progress has been made in the derivation of β-like cells from ES (D'Amour et al, 2006;Jiang et al, 2007;Kroon et al, 2008;Micallef et al, 2012;Nostro et al, 2011;Zhang et al, 2009) and iPS Park et al, 2008) cells, our understanding of the necessary signals required for the complete derivation of mature β cells in vitro is still limited (Naujok et al, 2011). To gain insight into the identity of cells born from in vitro differentiation, we evaluated the in vivo functional capacity of ES-derived cells at the DE and pancreatic progenitor stages.…”

Diabetes mellitus and cellular replacement therapy: Expected clinical potential and perspectives

“…This would be related with uniformness in transcription factors use and in the sufficiently differentiation affected techniques of ESC deriving. However, there is no consensus on common standard protocols regarding clinical approaches mentioned above [32,33] . Despite the contemporary statements are required improvement, they present requirement about uniform technology regarding differentiation methods of deriving pancreatic progenitor cells from pluripotent cells [25] .…”