PMID- 34926672
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220929
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 9
IP  - 21
DP  - 2021 Nov
TI  - Changes in the hepatic differentiation potential of human mesenchymal stem cells 
      aged in vitro.
PG  - 1628
LID - 10.21037/atm-21-4918 [doi]
LID - 1628
AB  - BACKGROUND: Due to their multipotency and ability for self-renewal, human 
      umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold great promise for 
      generating hepatocytes. Previous research has successfully generated hepatocytes 
      from early-passage [i.e., passage (P)3] hUC-MSCs; however, the populations of 
      early-passage cells are limited, and these cells cannot produce sufficient 
      functional hepatocytes for large-scale application in clinical therapy. Thus, a 
      thorough investigation of the hepatic differentiation potential of in vitro-aged 
      hUC-MSCs is needed. METHODS: hUC-MSCs were passaged in vitro and subcultured 
      every 3 days up to P8, and their morphology, proliferative capacity, 
      liver-specific marker expression, and liver function at the end of each passage 
      were analyzed. The efficiency of the hepatogenic differentiation of hUC-MSCs 
      driven by a functional hit 1 (FH1)-based strategy at different passages was also 
      evaluated. RESULTS: The in vitro-aged hUC-MSCs gradually displayed morphological 
      inhomogeneity, had reduced proliferative capability, and exhibited senescent 
      properties while maintaining adipogenic and osteogenic differentiation potential. 
      Additionally, senescence also decreased the expression of messenger RNA (mRNA) 
      levels in albumin (ALB) and alpha 1-antitrpsin (A1AT) in these cells and their 
      relative protein expression, which is the marker of a mature hepatocyte. The 
      liver function of the in vitro-aged hUC-MSCs also deteriorated gradually. 
      Finally, the percentage of hepatocyte-like cells (HLCs) generated from in 
      vitro-aged hUC-MSCs reduced significantly, and the mature hepatocyte functions, 
      such as ALB secretion, glycogen synthesis, low-density lipoprotein (LDL) intake, 
      and indocyanine green (ICG) uptake, also changed. CONCLUSIONS: hUC-MSCs possess 
      mature hepatocytes' specific markers and functions, which change gradually as 
      they undergo cell senescence. Due to the loss of these properties within in vitro 
      subcultures, the hepatic differentiation efficiency of in vitro-aged hUC-MSCs 
      decreased dramatically in the late passage (P8). The current study provides 
      valuable information can inform future research on 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 - Xiao, Shuai
AU  - Xiao 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 - 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
EIN - Ann Transl Med. 2022 Sep;10(17):946. PMID: 36172109
PMC - PMC8640908
OTO - NOTNLM
OT  - Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)
OT  - cell aging
OT  - hepatic differentiation
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at https://dx.doi.org/10.21037/atm-21-4918). The authors have no 
      conflicts of interest to declare.
EDAT- 2021/12/21 06:00
MHDA- 2021/12/21 06:01
PMCR- 2021/11/01
CRDT- 2021/12/20 06:19
PHST- 2021/08/31 00:00 [received]
PHST- 2021/10/13 00:00 [accepted]
PHST- 2021/12/20 06:19 [entrez]
PHST- 2021/12/21 06:00 [pubmed]
PHST- 2021/12/21 06:01 [medline]
PHST- 2021/11/01 00:00 [pmc-release]
AID - atm-09-21-1628 [pii]
AID - 10.21037/atm-21-4918 [doi]
PST - ppublish
SO  - Ann Transl Med. 2021 Nov;9(21):1628. doi: 10.21037/atm-21-4918.