A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Transplanted adult human hepatic stem/progenitor cells prevent histogenesis of advanced hepatic fibrosis in mice induced by carbon tetrachloride
Tekijät: Yanzhen Bi, Xiyu Liu, Chuanping Si, Ye Hong, Yongke Lu, Pengfei Gao, Yonghong Yang, Xiaobei Zhang, Yibo Wang, Huabao Xiong, Zhongping Duan, Yu Chen, Feng Hong
Kustantaja: E-CENTURY PUBLISHING CORP
Julkaisuvuosi: 2019
Journal: American Journal of Translational Research
Tietokannassa oleva lehden nimi: AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
Lehden akronyymi: AM J TRANSL RES
Vuosikerta: 11
Numero: 4
Aloitussivu: 2350
Lopetussivu: 2358
Sivujen määrä: 9
ISSN: 1943-8141
eISSN: 1943-8141
Verkko-osoite: http://www.ajtr.org/V11_No4.html
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/40705752
Transplantation of adult human hepatic stem/progenitor cells (hHSPCs) has been considered as an alternative therapy, replacing donor liver transplantation to treat liver cirrhosis. This study assessed the antifibrotic effects of hHSPCs in mice with fibrosis induced by carbon tetrachloride (CCI4) and examined the actions of hHSPCs on the fibrogenic activity of human hepatic stellate cells (HSCs) in a coculture system. Isolated hHSPCs expressed stem/progenitor cell phenotypic markers. Mice were given CCl4 (twice weekly for 7 weeks) and hHSPC transplantation weekly. CCl4 induced advanced fibrosis (bridging fibrosis and cirrhosis) in mice, which was prevented by hHSPC transplantation. The liver of hHSPC-transplanted mice showed only occasional short septa and focal parenchymal fibrosis, and a 50% reduction in hepatic collagen, assessed by Sirius red stain histomorphometry. Moreover, the proteins for a-smooth muscle actin (alpha-SMA) and collagen I were decreased. While alpha-SMA, collagen alpha 1(I), and tissue inhibitor of metalloproproteinase-1 mRNAs were decreased, matrix metalloproteinase (MMP)-1 mRNA was increased, consistent with decreased fibrogenesis. MMP-2 and transforming growth factor-beta were not affected. Alanine aminotransferase and aspartate aminotransferase were lower, suggesting improvement of liver function/damage. In coculture, hHSPCs elicited changes of alpha-SMA and fibrogenic molecules in HSCs similar to those observed in vivo, providing evidence for a functional link between hHSPCs and HSCs. A decreased HSC proliferation was noted. Thus, transplantation of hHSPCs prevents histogenesis of advanced liver fibrosis caused by CCl4. hHSPCs mediate down-regulation of HSC activation coincident with modulation of fibrogenic molecule expression, leading to suppression of fibrogenesis both in vivo and in vitro.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
