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In vitro pancreatic islet cluster expansion facilitated by hormones and chemicals

By Jing-Yu Lin, Jie Cheng, Ya-Qin Du, Wei Pan, Zhong Zhang, Jin Wang, Jie An, Fan Yang, Yun-Fei Xu, Hui Lin, Wen-Tao An, Jia Wang, Zhao Yang, Ren-Jie Chai, Xue-Ying Sha, Hui-Li Hu, Jin-Peng Sun, Xiao Yu

Posted 16 Dec 2019
bioRxiv DOI: 10.1101/2019.12.16.873596 (published DOI: 10.1038/s41421-020-0159-x)

Tissue regeneration, such as pancreatic islet tissue propagation in vitro, could serve as a promising strategy for diabetes therapy and personalized drug testing. However, such a protocol has not been realized yet. Propagation could be divided by two steps, which are: (1) expansion in vitro and (2) repeat passaging. Even the in vitro expansion of the islet has not been achieved to date. Here, we describe a method to enable the expansion of islet clusters isolated from pregnant mice or wild-type rats by employing a combination of specific regeneration factors and chemical compounds in vitro. The expanded islet clusters expressed insulin, glucagon and somatostatin, which are markers corresponding to pancreatic β cells, α cells and δ cells, respectively. These different types of cells grouped together, were spatially organized and functioned similarly to primary islets. Further mechanistic analysis revealed that forskolin in our recipe contributed to renewal and regeneration, whereas exendin4 was essential for preserving islet cell identity. Our results provide a novel method for the in vitro expansion of islet clusters, which is an important step forward in developing future protocols and medium used for islet tissue propagation in vitro. Such method is important for future regenerative diabetes therapies and personalized medicine using large amounts of pancreatic islets derived from the same person.

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