PMID- 29290652 OWN - NLM STAT- MEDLINE DCOM- 20180814 LR - 20181202 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 23 IP - 46 DP - 2017 Dec 14 TI - In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis. PG - 8152-8168 LID - 10.3748/wjg.v23.i46.8152 [doi] AB - AIM: To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. METHODS: A CCl(4)-induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. RESULTS: We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo. Functionally, the transplantation of hUC-MSCs to CCl(4)-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. CONCLUSION: Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl(4)-induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis. FAU - Zhang, Guo-Zun AU - Zhang GZ AD - Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China. FAU - Sun, Hui-Cong AU - Sun HC AD - Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China. FAU - Zheng, Li-Bo AU - Zheng LB AD - Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China. FAU - Guo, Jin-Bo AU - Guo JB AD - Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China. FAU - Zhang, Xiao-Lan AU - Zhang XL AD - Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China. xiaolanzh@hb2h.com. LA - eng PT - Journal Article PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - CL2T97X0V0 (Carbon Tetrachloride) SB - IM MH - Animals MH - Carbon Tetrachloride/toxicity MH - *Cell Differentiation MH - Cells, Cultured MH - Disease Models, Animal MH - Extracellular Matrix/metabolism MH - Fibrosis MH - Hepatic Stellate Cells/physiology MH - Hepatocytes/physiology MH - Humans MH - Liver/cytology/drug effects/*pathology MH - Liver Cirrhosis/blood/chemically induced/pathology/*therapy MH - Liver Function Tests MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*physiology MH - Rats MH - Rats, Wistar MH - Umbilical Cord/cytology PMC - PMC5739922 OTO - NOTNLM OT - Collagen metabolism OT - Differentiation OT - Hepatocyte OT - Liver fibrosis/cirrhosis OT - Mesenchymal stem cells COIS- Conflict-of-interest statement: We declare that there are no conflicts of interest to disclose. EDAT- 2018/01/02 06:00 MHDA- 2018/08/15 06:00 PMCR- 2017/12/14 CRDT- 2018/01/02 06:00 PHST- 2017/03/27 00:00 [received] PHST- 2017/05/29 00:00 [revised] PHST- 2017/08/09 00:00 [accepted] PHST- 2018/01/02 06:00 [entrez] PHST- 2018/01/02 06:00 [pubmed] PHST- 2018/08/15 06:00 [medline] PHST- 2017/12/14 00:00 [pmc-release] AID - 10.3748/wjg.v23.i46.8152 [doi] PST - ppublish SO - World J Gastroenterol. 2017 Dec 14;23(46):8152-8168. doi: 10.3748/wjg.v23.i46.8152.