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

Publication date: 3 August 2017
Source:Cell Stem Cell, Volume 21, Issue 2
Author(s): Jiping Yue, Xuewen Gou, Yuanyuan Li, Barton Wicksteed, Xiaoyang Wu
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.

Graphical abstract

Teaser

Wu and colleagues show that engineered epidermal progenitor cells can function as a gene therapy vehicle. Using an immunocompetent skin transplantation model, they show skin grafts that secrete GLP-1 in a controllable manner can normalize body weight and blood glucose levels in diet-induced obese and diabetic mice.


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