Chemical combinations potentiate human pluripotent stem cell-derived 3D pancreatic progenitor clusters toward functional β cells.

Autor: Liu, Haisong, Li, Ronghui, Liao, Hsin-Kai, Min, Zheying, Wang, Chao, Yu, Yang, Shi, Lei, Dan, Jiameng, Hayek, Alberto, Martinez Martinez, Llanos, Nuñez Delicado, Estrella, Izpisua Belmonte, Juan Carlos
Předmět:
Zdroj: Nature Communications; 6/7/2021, Vol. 12 Issue 1, p1-10, 10p
Abstrakt: 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. Human pluripotent stem cell (hPSC) derived pancreatic beta cells are a promising and potentially limitless source for cell replacement therapy. Here the authors perform stage-wise chemical screening to develop an improved protocol for hPSC differentiation to functional pancreatic beta cells at high efficiency. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index