Journal
STEM CELL RESEARCH
Volume 24, Issue -, Pages 61-68Publisher
ELSEVIER
DOI: 10.1016/j.scr.2017.08.010
Keywords
Diabetes; Induced pluripotent stem cell; Pancreatic progenitor cell; Small molecule; Proliferation
Funding
- Takeda Science Foundation
- Suzuken Memorial Foundation
- Mitsui Life Social Welfare Foundation
- Life Science Foundation of Japan
- Japan Diabetes Foundation
- JSPS KAKENHI Grant [17J07622, 15K09385]
- Japan Agency for Medical Research and Development (AMED) through its research grant Core Center for iPS Cell Research, Research Center Network for Realization of Regenerative Medicine
- JSPS
- Grants-in-Aid for Scientific Research [17J07622, 15K09385] Funding Source: KAKEN
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While pancreatic islet transplantation achieves insulin independence in type 1 diabetes (T1D) patients, its widespread application is limited by donor tissue scarcity. Pancreatic progenitor cells (PPCs) give rise to all cell types in the pancreas during development. PPCs derived from human pluripotent stem cells have been shown to differentiate into functional beta cells both in vitro and in vivo, and to reverse hyperglycemia, at least in mice. Therefore, PPCs have great potential to serve as an alternative cell source for cell therapy, and the identification of compounds that facilitate PPC proliferation could provide stable and large-scale pancreatic cell preparation systems in clinical settings. Here, we developed and performed cell-based screens to identify small molecules that induce the proliferation of hiPSC-derived PDX1-expressing PPCs. The screening identified AT7867, which promoted PPC proliferation approximately five-fold within six days through the maintenance of a high Ki67(+) cell ratio. The induced proliferation by AT7867 does not result in DNA damage, as revealed by pHH2AX staining, and is observed specifically in PPCs but not other cell types. The established platform utilizing small molecules for PPC proliferation may contribute to the development of cell therapy for T1D using a regenerative medicine approach. (C) 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license
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