PMID- 37413859
OWN - NLM
STAT- MEDLINE
DCOM- 20230728
LR  - 20230728
IS  - 1532-3072 (Electronic)
IS  - 0040-8166 (Linking)
VI  - 83
DP  - 2023 Aug
TI  - Comparison of two hepatocyte differentiation protocols in human umbilical cord 
      mesenchymal stem cells: In vitro study.
PG  - 102153
LID - S0040-8166(23)00141-6 [pii]
LID - 10.1016/j.tice.2023.102153 [doi]
AB  - Human umbilical cord mesenchymal stromal cells (HUCMSCs) are an emerging source 
      of cell therapy due to their self-renew and differentiation ability. They can 
      differentiate into three germ layers, including the potential to generate 
      hepatocytes. This study determined the transplantation efficiency and suitability 
      of HUCMSCs-derived hepatocyte-like cells (HLCs) for their therapeutic application 
      for liver diseases. This study aims to formulate ideal conditions to induce 
      HUCMSCs into the hepatic lineage and investigate the efficiency of the 
      differentiated HLCs based on their expression characteristics and capacity to 
      integrate into the damaged liver of CCl4-challenged mice. Hepatocyte growth 
      factor (HGF) and Activin A, Wnt3a were found to optimally promote the endodermal 
      expansion of HUCMSCs, which showed phenomenal expression of hepatic markers upon 
      differentiation in the presence of oncostatin M and dexamethasone. HUCMSCs 
      expressed MSC-related surface markers and could undergo tri-lineage 
      differentiations. Two hepatogenic differentiation protocols (differentiated 
      hepatocyte protocol 1 [DHC1]: 32 days and DHC2: 15 days) were experimented with. 
      The proliferation rate was faster in DHC2 than in DHC1 on day 7 of 
      differentiation. The migration capability was the same in both DHC1 and DHC2. 
      Hepatic markers like CK18, CK19, ALB, and AFP were upregulated. The mRNA levels 
      of albumin, alpha1AT, alphaFP, CK18, TDO2, CYP3A4, CYP7A1, HNF4A, CEBPA, PPARA, and PAH 
      were even higher in the HUCMSCs-derived HCLs than in the primary hepatocytes. 
      Western blot confirmed HNF3B and CK18 protein expression in a step-wise manner 
      differentiated from HUCMSCs. The metabolic function of differentiated hepatocytes 
      was evident by increasing PAS staining and urea production. Pre-treating HUCMSCs 
      with a hepatic differentiation medium containing HGF can drive their 
      differentiation towards endodermal and hepatic lineages, enabling efficient 
      integration into the damaged liver. This approach represents a potential 
      alternative protocol for cell-based therapy that could enhance the integration 
      potential of HUCMSC-derived HLCs.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Shibu, Marthandam Asokan
AU  - Shibu MA
AD  - Department of Biotechnology, Bharathiar University, Coimbatore, India.
FAU - Huang, Chih-Yang
AU  - Huang CY
AD  - Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi 
      Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; Graduate 
      Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan; 
      Department of Biological Science and Technology, Asia University, Taichung 413, 
      Taiwan; Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi 
      University of Science and Technology, Hualien 970, Taiwan; Department of Medical 
      Research, China Medical University Hospital, China Medical University Hospital, 
      Taichung 404, Taiwan.
FAU - Ding, Dah-Ching
AU  - Ding DC
AD  - Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Tzu 
      Chi University, Hualien 970, Taiwan; Graduate Institute of Medical Science, Tzu 
      Chi University, Hualien 970, Taiwan. Electronic address: dah1003@yahoo.com.tw.
LA  - eng
PT  - Journal Article
DEP - 20230630
PL  - Scotland
TA  - Tissue Cell
JT  - Tissue & cell
JID - 0214745
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Liver
MH  - Hepatocytes/metabolism
MH  - Cell Differentiation
MH  - *Mesenchymal Stem Cells
MH  - Umbilical Cord
OTO - NOTNLM
OT  - Basic fibroblast growth factor
OT  - Endoderm
OT  - Epidermal growth factor
OT  - Hepatic markers
OT  - Hepatocyte growth factor
OT  - Liver cirrhosis
OT  - Liver transplantation
OT  - Regenerative medicine
COIS- Declaration of Conflicting Interest The authors declared no potential conflicts 
      of interest with respect to this article's research, authorship, and/or 
      publication.
EDAT- 2023/07/07 01:05
MHDA- 2023/07/28 06:43
CRDT- 2023/07/06 18:06
PHST- 2023/04/09 00:00 [received]
PHST- 2023/06/28 00:00 [revised]
PHST- 2023/06/29 00:00 [accepted]
PHST- 2023/07/28 06:43 [medline]
PHST- 2023/07/07 01:05 [pubmed]
PHST- 2023/07/06 18:06 [entrez]
AID - S0040-8166(23)00141-6 [pii]
AID - 10.1016/j.tice.2023.102153 [doi]
PST - ppublish
SO  - Tissue Cell. 2023 Aug;83:102153. doi: 10.1016/j.tice.2023.102153. Epub 2023 Jun 
      30.