Rapid and high-efficiency generation of mature functional hepatocyte-like cells from adipose-derived stem cells by a three-step protocol

Fen Xu; Junli Liu; Jie Deng; Xiaolei Chen; Yuan Wang; Pengchao Xu; Lin Cheng; Yanli Fu; Fuyi Cheng; Yunqi Yao; Yujing Zhang; Meijuan Huang; Dechao Yu; Yuquan Wei; Hongxin Deng

doi:10.1186/s13287-015-0181-3

Rapid and high-efficiency generation of mature functional hepatocyte-like cells from adipose-derived stem cells by a three-step protocol

Stem Cell Res Ther. 2015 Oct 5:6:193. doi: 10.1186/s13287-015-0181-3.

Authors

Fen Xu¹, Junli Liu², Jie Deng³, Xiaolei Chen⁴, Yuan Wang⁵, Pengchao Xu⁶, Lin Cheng⁷, Yanli Fu⁸, Fuyi Cheng⁹, Yunqi Yao¹⁰, Yujing Zhang¹¹, Meijuan Huang^{12

13}, Dechao Yu¹⁴, Yuquan Wei¹⁵, Hongxin Deng¹⁶

Affiliations

¹ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
² State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
³ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
⁴ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
⁵ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
⁶ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
⁷ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
⁸ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
⁹ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
¹⁰ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
¹¹ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
¹² State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
¹³ Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan, 610041, P.R. China. [email protected].
¹⁴ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
¹⁵ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].
¹⁶ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, section3, Renmin South Road, Chengdu, 610041, P.R. China. [email protected].

Abstract

The generation of functional hepatocytes is a major challenge for regenerative medicine and drug discovery. Here we show a method that facilitates generation of induced functional hepatocytes (iHeps) from adipose-derived stem cells (ADSCs) within 9 days. iHeps express hepatocytic gene programs and display functions characteristic of mature hepatocytes, including cytochrome P450 enzyme activity. Upon transplantation into mice with carbon tetrachloride (CCl4)-induced acute fulminant liver failure, iHeps restore the liver function and prolong survival. The work could contribute to the development of alternative strategies to obtain nonhepatic cell-derived mature hepatocytes with potential for biomedical and pharmaceutical applications.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Abdominal Fat / cytology
Adult Stem Cells / physiology*
Animals
Carbon Tetrachloride
Cell Differentiation*
Cells, Cultured
Female
Hepatocytes / physiology*
Hepatocytes / transplantation
Liver Failure / chemically induced
Liver Failure / therapy
Mice, Inbred BALB C
Mice, Nude
Neoplasm Transplantation
Rats, Inbred Lew

Substances

Carbon Tetrachloride

Grants and funding

N01AA21004/AA/NIAAA NIH HHS/United States