잠시만 기다려 주세요. 로딩중입니다.

Infusion of Human Mesenchymal Stem Cells Improves Regenerative Niche in Thioacetamide-Injured Mouse Liver

Tissue Engineering and Regenerative Medicine 2020년 17권 5호 p.671 ~ 682
Kao Ying-Hsien, Lin Yu-Chun, Lee Po-Huang, Lin Chia-Wei, Chen Po-Han, Tai Tzong-Shyuan, Chang Yo-Chen, Chou Ming-Huei, Chang Chih-Yang, Sun Cheuk-Kwan,
소속 상세정보
 ( Kao Ying-Hsien ) - E-DA Hospital Department of Medical Research
 ( Lin Yu-Chun ) - E-Da Hospital Department of Surgery
 ( Lee Po-Huang ) - E-Da Hospital Department of Surgery
 ( Lin Chia-Wei ) - Kaohsiung Medical University Department of Ophthalmology
 ( Chen Po-Han ) - E-DA Hospital Department of Medical Research
 ( Tai Tzong-Shyuan ) - E-DA Hospital Department of Medical Research
 ( Chang Yo-Chen ) - Kaohsiung Medical University Department of Ophthalmology
 ( Chou Ming-Huei ) - Chang Gung University College of Medicine Graduate Institute of Clinical Medical Sciences
 ( Chang Chih-Yang ) - E-Da Hospital Department of Gynecology and Obstetrics
 ( Sun Cheuk-Kwan ) - E-DA Hospital Department of Medical Research

Abstract


Background: This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism.

Methods: Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies.

Results: WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-β1-stimulation in Smad2 phosphorylation and RhoA upregulation.

Conclusion: These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.

키워드

Human umbilical cord; Hepatotoxin; Liver fibrosis; Plasma fibronectin; Wharton’s jelly tissue

원문 및 링크아웃 정보

등재저널 정보