Pancreatic β cells are the only cell source for insulin production. Dysregulation or loss of β cells leads to diabetes. In the last 20 years, islets transplantation has been considered a promising cell therapy approach for diabetic patients. However, due to the shortage of cadaveric donors, islets transplantation remains a limited therapy approach.
Pancreatic islet cells exhibit limited proliferation in adults. It remains unclear whether the adult islet contains stem/progenitor cells that contribute to β cell mass maintenance during homeostasis and regeneration. In vitro, it has been proven challenging to generate functional β cells.
In a recent study published in Cell, a research team led by Dr. ZENG Yi from Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, identified the stem/progenitor cell in adult mouse pancreatic islets, and established an in vitro culture system for the long-term expansion of functional islet organoids from these stem/progenitor cells.
Through single-cell RNA-sequencing, the researchers identified a novel population in pancreatic islets marked by the expression of surface Procr (Protein C Receptor). By genetic lineage tracing experiments in vivo, they further demonstrated their stem/progenitor cell properties.
Besides, the researchers cultured the Procr+ stem/progenitor cells in vitro, and established an in vitro system that can derive functional islet organoids for long-term.
These islet organoids displayed similar cellular composition and molecular features with mouse islets. They are glucose-responsive and insulin secreting. They can be cultured in vitro for long-term, maintaining exponentially growth. When transplanted into diabetic mice, they can reverse diabetes in vivo.
This study identifies a novel islet stem/progenitor cell population in adult mouse pancreas, and establishes an in vitro method for the induction and long-term expansion of islet-like organoids. This progenitor population may be explored for their existence in human and for treatment of diabetes.
Graphical Abstract: (Left) identification of Procr+ islet stem/progenitor cells in mouse pancreas; (Right) generation and long-term expansion of funcitonal islet organoids.
Reference: https://doi.org/10.1016/j.cell.2020.02.048
Contact: yzeng@sibcb.ac.cn
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