3 years ago

Engineered Epidermal Progenitor Cells Can Correct Diet-Induced Obesity and Diabetes

Engineered Epidermal Progenitor Cells Can Correct Diet-Induced Obesity and Diabetes
Xiaoyang Wu, Barton Wicksteed, Yuanyuan Li, Xuewen Gou, Jiping Yue

Summary

Somatic gene therapy is a promising approach for treating otherwise terminal or debilitating diseases. The human skin is a promising conduit for genetic engineering, as it is the largest and most accessible organ, epidermal autografts and tissue-engineered skin equivalents have been successfully deployed in clinical applications, and skin epidermal stem/progenitor cells for generating such grafts are easy to obtain and expand in vitro. Here, we develop skin grafts from mouse and human epidermal progenitors that were engineered by CRISPR-mediated genome editing to controllably release GLP-1 (glucagon-like peptide 1), a critical incretin that regulates blood glucose homeostasis. GLP-1 induction from engineered mouse cells grafted onto immunocompetent hosts increased insulin secretion and reversed high-fat-diet-induced weight gain and insulin resistance. Taken together, these results highlight the clinical potential of developing long-lasting, safe, and versatile gene therapy approaches based on engineering epidermal progenitor cells.

Publisher URL: http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(17)30274-6

DOI: 10.1016/j.stem.2017.06.016

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