Engineered Epidermal Progenitor Cells Can Correct Diet-Induced Obesity and Diabetes.,Cell Stem Cell

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Engineered Epidermal Progenitor Cells Can Correct Diet-Induced Obesity and Diabetes.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2017-08-03 , DOI: 10.1016/j.stem.2017.06.016
Jiping Yue ₁ , Xuewen Gou ₁ , Yuanyuan Li ₁ , Barton Wicksteed ₂ , Xiaoyang Wu ₁

Affiliation

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.

中文翻译：

工程化的表皮祖细胞可以纠正饮食诱发的肥胖和糖尿病。

体细胞基因疗法是治疗其他疾病或使人衰弱的有前途的方法。人体皮肤是基因工程的有希望的渠道，因为它是最大和最容易接近的器官，表皮自体移植物和组织工程化的皮肤等效物已成功应用于临床，并且用于生成此类移植物的皮肤表皮干/祖细胞很容易获得并扩大体外。在这里，我们开发了小鼠和人类表皮祖细胞的皮肤移植物，这些皮肤移植物由CRISPR介导的基因组编辑工程化，可控制地释放GLP-1（胰高血糖素样肽1），GLP-1是调节血糖稳态的关键降钙素。从移植到具有免疫能力的宿主的工程小鼠细胞中诱导GLP-1可以增加胰岛素分泌，并逆转高脂饮食诱导的体重增加和胰岛素抵抗。综上所述，这些结果凸显了基于工程化的表皮祖细胞开发持久，安全且通用的基因治疗方法的临床潜力。

更新日期：2017-08-03

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