PMID- 34422999
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220828
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 9
IP  - 13
DP  - 2021 Jul
TI  - Functional hit 1 (FH1)-based rapid and efficient generation of functional 
      hepatocytes from human mesenchymal stem cells: a novel strategy for hepatic 
      differentiation.
PG  - 1087
LID - 10.21037/atm-21-2829 [doi]
LID - 1087
AB  - BACKGROUND: Because the liver is central to the physiology of the body, primary 
      hepatocytes are widely used in liver pathology and physiological research, such 
      as liver drug screening, bioartificial liver support system, and cell therapy for 
      liver diseases. However, the source of primary hepatocytes is limited. We 
      describe a novel non-transgenic protocol that facilitates the rapid generation of 
      hepatocyte-like cells from human umbilical cord-derived mesenchymal stem cells 
      (hUC-MSCs), providing a new source of functional hepatocytes. METHODS: In this 
      study, we used hUC-MSCs and human induced pluripotent cells (iPSCs) derived 
      mesenchymal stem cells (iMSCs) to investigate the new induction strategy. Passage 
      3 MSCs were induced into hepatocyte-like cells using small-molecule compounds 
      combined with cell factors in vitro. Functional hit 1 (FH1), a promising small 
      molecule compound was achieved to replace HGF in the hepatocyte maturation stage 
      to induce the hepatocyte-like cells differentiation. RESULTS: We rapidly induced 
      hUC-MSCs and human iMSCs into hepatocyte-like cells within 10 days in vitro, and 
      the cells were morphologically similarly to both hepatocytes derived from the 
      hepatocyte growth factor (HGF)-based method and the primary hepatocytes. They 
      expressed mature hepatocyte special genes and achieved functions such as glycogen 
      storage, albumin expression, urea secretion, cytochrome P450 activity, 
      Low-density lipoprotein (LDL) uptake, and indocyanine green (ICG) uptake. 
      CONCLUSIONS: We successfully established a small-molecule protocol without using 
      HGF to differentiate MSCs into hepatocyte-like cells, which provides a rapid and 
      cost-effective platform for in vitro studies of liver disease.
CI  - 2021 Annals of Translational Medicine. All rights reserved.
FAU - Luo, Sang
AU  - Luo S
AD  - State Key Laboratory of Virology, School of Life Sciences, Wuhan University, 
      Wuhan, China.
FAU - Ai, Yang
AU  - Ai Y
AD  - State Key Laboratory of Virology, School of Life Sciences, Wuhan University, 
      Wuhan, China.
FAU - Xiao, Shuai
AU  - Xiao S
AD  - State Key Laboratory of Virology, School of Life Sciences, Wuhan University, 
      Wuhan, China.
FAU - Wang, Ben
AU  - Wang B
AD  - State Key Laboratory of Virology, School of Life Sciences, Wuhan University, 
      Wuhan, China.
FAU - Wang, Yefu
AU  - Wang Y
AD  - State Key Laboratory of Virology, School of Life Sciences, Wuhan University, 
      Wuhan, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC8339809
OTO - NOTNLM
OT  - Functional hit 1 (FH1)
OT  - Hepatocyte differentiation
OT  - human mesenchymal stem cells (human MSCs)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at https://dx.doi.org/10.21037/atm-21-2829). The authors have no 
      conflicts of interest to declare.
EDAT- 2021/08/24 06:00
MHDA- 2021/08/24 06:01
PMCR- 2021/07/01
CRDT- 2021/08/23 06:37
PHST- 2021/05/19 00:00 [received]
PHST- 2021/06/25 00:00 [accepted]
PHST- 2021/08/23 06:37 [entrez]
PHST- 2021/08/24 06:00 [pubmed]
PHST- 2021/08/24 06:01 [medline]
PHST- 2021/07/01 00:00 [pmc-release]
AID - atm-09-13-1087 [pii]
AID - 10.21037/atm-21-2829 [doi]
PST - ppublish
SO  - Ann Transl Med. 2021 Jul;9(13):1087. doi: 10.21037/atm-21-2829.