Rapid and high-efficiency generation of mature functional hepatocyte-like cells from adipose-derived stem cells by a three-step protocol
Authors: Yujing Zhang
Meijuan Huang
Junli Liu
Dechao Yu
Fen Xu
Yanli Fu
Yuan Wang
Pengchao Xu
Lin Cheng
Jie Deng
Xiaolei Chen
Yuquan Wei
Fuyi Cheng
Yunqi Yao
Hongxin Deng
Journal: Stem Cell Research & Therapy (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: functional hepatocytes; regenerative medicine; drug discovery; induced functional hepatocytes; adipose-derived stem cells
Affiliations: 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. ., Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan, 610041, P.R. China. .

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. 

Retracted: No

PubPeer comments:
 Fig 3 E PAS and ICG panels have unexpected overlap. How to explain it? Please make comment. Thanks!![file] , 
 Thank you very much for your comments! For this problem, we have checked the original data and found that the two experiments used the same batch of ADSC cells. In other words, ICG was added to the cell culture medium to observe the uptake of ICG by ADSC. After PBS rinsing, the photos were taken, and the results showed negative. ICG uptake and glycogen synthesis are two independent metabolic functions that exist simultaneously in certain cells (such as hepatocytes). These ADSC cells were directly fixed for glycogen synthesis detection (PAS staining), so the images of the two experiments might overlap. However, it should be noted that ICG uptake and PAS staining had been repeated several times in our study. Furthermore, according to our data, the results of ICG uptake and PAS staining for ADSC, whether using the same batch of cells or using two batches of cells separately, were negative. We are sorry to have chosen the images that make readers confused. , 
 #2 Thanks for your reply. Below please find the another duplicate. Fig 1b is the morf. of ADSCs at passage 3, suppose you use this plate for ICG and PAS experiment. For ICG experiment, you incubate the media containing ICG for 1h at 37C. For PAS staining, you said the cells were fixed prior to the staining. So I have 2 questions: 1. Why the ADSCs has the same morf. after 1h incubation? ICG staining photo is same with Fig 1b un-staining 1 hour earlier 2. Why the morf. after fix is same with unfix group? PAS staining photo is same with Fig1b and ICG photos Please make comment. Thanks! ![file] , 
 Thank you very much for your comment! Fig.1b is to show the typical spindle morphology of ADSC. We checked the original data carefully and found that we mistakenly placing the ICG image on the position of Fig.1b. We apologize for this mistake, and thank you for helping us find it! We will apply to the journal for a corrigendum to update the image in fig.1b. For the problem of ADSC morphology, the PAS fixative is very mild and the fixation time is relatively short, which has no obvious influence on the cell morphology. ,