Chemical combinations potentiate human pluripotent stem cell-derived 3D pancreatic progenitor clusters toward functional β cells
Open Access
- 7 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 12 (1), 1-10
- https://doi.org/10.1038/s41467-021-23525-x
Abstract
Human pluripotent stem cell (hPSC)-derived pancreatic β cells are an attractive cell source for treating diabetes. However, current derivation methods remain inefficient, heterogeneous, and cell line dependent. To address these issues, we first devised a strategy to efficiently cluster hPSC-derived pancreatic progenitors into 3D structures. Through a systematic study, we discovered 10 chemicals that not only retain the pancreatic progenitors in 3D clusters but also enhance their potentiality towards NKX6.1+/INS+ β cells. We further systematically screened signaling pathway modulators in the three steps from pancreatic progenitors toward β cells. The implementation of all these strategies and chemical combinations resulted in generating β cells from different sources of hPSCs with high efficiency. The derived β cells are functional and can reverse hyperglycemia in mice within two weeks. Our protocol provides a robust platform for studying human β cells and developing hPSC-derived β cells for cell replacement therapy.This publication has 31 references indexed in Scilit:
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