New Opportunities: Harnessing Induced Pluripotency for Discovery in Diabetes and Metabolism

Abstract

The landmark discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka has transformed regenerative biology. Previously, insights into the pathogenesis of chronic human diseases have been hindered by the inaccessibility of patient samples. However, scientists are now able to convert patient fibroblasts into iPSCs and differentiate them into disease-relevant cell types. This ability opens new avenues for investigating disease pathogenesis and designing novel treatments. In this review, we highlight the uses of human iPSCs to uncover the underlying causes and pathological consequences of diabetes and metabolic syndromes, multi-factorial diseases whose etiologies have been difficult to unravel using traditional methodologies.

Comparable Generation of Activin-Induced Definitive Endoderm via Additive Wnt or BMP Signaling in Absence of Serum

“…Given the explosion in diabetes and its complications worldwide, the directed differentiation of hPSCs into definitive endoderm (DE) and subsequently pancreatic cells is of immense interest (Teo et al., 2013a). In 2005, Novocell (now ViaCyte) reported the ability to derive > 80% of DE from hESCs with the use of 100 ng/ml Activin A (hereafter referred to as “Activin”) in the presence of 0.2%–2% fetal bovine serum (FBS; D’Amour et al., 2005).…”

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

“…Current therapeutic approaches for both type 1 and type 2 diabetes are primarily focused on enhancing insulin secretion and/or insulin supplementation. Among the strategies that are continually evolving to preserve and/or replenish the functional beta cell mass, differentiation of embryonic and adult induced pluripotent stem cells in vitro [2] is appealing but is currently faced with limited efficiency in generating mature glucose-responsive beta cells. Other approaches include enhancing in vivo regeneration, either by improving resistance against destructive signals and apoptotic T. Mezza : R. N. Kulkarni (*) pathways or by careful and selective proliferation of existing beta cells, and differentiation and de-differentiation processes have recently been suggested to revive beta cells [3].…”

Vascular diseases await translation of blood vessels engineered from stem cells

“…From a developmental perspective, however, it is known that the endothelium is instructive in providing signals that determine morphogenesis and cell differentiation of the liver and pancreas (78). The value of obtaining diabetic hiPSC-derived vascular cells would be most robust in examining monogenic diabetes, such as type 1 diabetes (T1D) or maturity-onset diabetes of the young (MODY) (79). We have been successful in isolating hiPSC-derived ECs and PVCs from T1D and MODY cases (8).…”