Engineered Hair Follicle Mesenchymal Stem Cells Overexpressing Controlled-Release Insulin Reverse Hyperglycemia in Mice with Type l Diabetes

Cell Transplantation

Article

Xiangwei Meng¹  Gang Li²  Lixing Tian³  Wenyue Jiang⁴  Guifang Zhao⁵  Yulin Li⁵  Jin Yu Liu⁵  Pengdong Li⁵  Chunling Wu⁵  Shaowei Lan⁵  Feilin Liu⁵ 

[1] Department of Gastroenterology, Fist Hospital of Jilin University, Changchun, Jilin, P.R. China;Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, P.R. China;Department of Pathology, Changchun Obstetrics and Gynecology Hospital, Changchun, Jilin, P.R. China;School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin, P.R. China;The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, P.R. China;

关键词: Mesenchymal stem cells;    Hair follicles;    Gene therapy;    Lentivirus;    Type 1 diabetes;   

DOI  :  10.3727/096368914X681919

 received in 2013-12-18, accepted in 2014-05-10,  发布年份 2015

来源: Sage Journals

【 摘 要 】

Genetically engineered stem cells that overexpress genes encoding therapeutic products can be exploited to correct metabolic disorders by repairing and regenerating diseased organs or restoring their function. Hair follicles are readily accessible and serve as a rich source of autologous stem cells for cell-based gene therapy. Here we isolated mesenchymal stem cells from human hair follicles (HF-MSCs) and engineered them to overexpress the human insulin gene and release human insulin in a time- and dose-dependent manner in response to rapamycin. The engineered HF-MSCs retained their characteristic cell surface markers and retained their potential to differentiate into adipocytes and osteoblasts. When mice with streptozotocin-induced type 1 diabetes were engrafted with these engineered HF-MSCs, these cells expressed and released a dose of human insulin, dramatically reversed hyperglycemia, and significantly reduced death rate. Moreover, the engineered HF-MSCs did not form detectable tumors throughout the 120-day animal tests in our experiment. Our results show that HF-MSCs can be used to safely and efficiently express therapeutic transgenes and therefore show promise for cell-based gene therapy of human disease.

【 授权许可】

Unknown   
© 2015 Cognizant Comm. Corp.

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