Human pancreatic beta-like cells converted from fibroblasts

Abstract

Pancreatic beta cells are of great interest for biomedical research and regenerative medicine. Here we show the conversion of human fibroblasts towards an endodermal cell fate by employing non-integrative episomal reprogramming factors in combination with specific growth factors and chemical compounds. On initial culture, converted definitive endodermal progenitor cells (cDE cells) are specified into posterior foregut-like progenitor cells (cPF cells). The cPF cells and their derivatives, pancreatic endodermal progenitor cells (cPE cells), can be greatly expanded. A screening approach identified chemical compounds that promote the differentiation and maturation of cPE cells into functional pancreatic beta-like cells (cPB cells) in vitro. Transplanted cPB cells exhibit glucose-stimulated insulin secretion in vivo and protect mice from chemically induced diabetes. In summary, our study has important implications for future strategies aimed at generating high numbers of functional beta cells, which may help restoring normoglycemia in patients suffering from diabetes.

MicroRNAs: An adaptive mechanism in the pancreatic β-cell…and beyond?

“…To bring additional clarity to this picture, future studies should address the global temporal regulation and stability of β-cell transcripts in response to changes in extracellular glucose concentrations. The crosslinking protocols that have been developed to identify target sites of miRNAs and RNA-binding proteins can be implemented on the stem cell and fibroblast models now available to understand how non-coding RNAs function in as cells differentiate into insulin-producing β-cells [47] [48] [49] [50]. Improving these protocols to optimize the functional properties and viability of these β-cell models remain a top priority for the development of future therapeutic strategies for combating diabetes.…”

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

“…32,33 Functional b-like cells, have been recently obtained in vitro from human adipose tissue mesenchymal stem cells and from foreskin fibroblasts, although the most convenient sources are adipose, skin, or blood cells. [34][35][36] However, these artificially generated b-like cells do not completely recapitulate the phenotype and functions of an original b cells, thus reducing the therapeutic efficacy. Second, it needs to be ascertained whether, after transplantation, reprogrammed b-like cells survive and maintain the differentiated phenotype long enough to warrant good quality to the patient's life.…”

Premature ovarian failure and tissue engineering

“…They are a vital source of renewable autologous cells in tissue engineering and regenerative medicine and hold promises for tissue engineering and cell therapy (Wang et al, ; Zhao, Zhang, Rong, & Xu, ). There are some applications of iPSCs in tissue engineering which improve disease symptoms, such as eye defects, diabetes, and lung degeneration (Dye et al, ; Howden et al, ; Tsai et al, ; Yang et al, ; Zhu et al, ).…”