title: The therapeutic potential of human umbilical mesenchymal stem cells from Wharton's jelly in the treatment of rat liver fibrosis.
abstract: We investigated the effect of human umbilical mesenchymal stem cells (HUMSCs) from Wharton's jelly on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Rats were treated with CCl4 for 4 weeks, and this was followed by a direct injection of HUMSCs into their livers. After 4 more weeks of CCl4 treatment (8 weeks in all), rats with HUMSC transplants [CCl4 (8W)+HUMSC liver] exhibited a significant reduction in liver fibrosis, as evidenced by Sirius red staining and a collagen content assay, in comparison with rats treated with CCl4 for 8 weeks without HUMSC transplants [CCl4 (8W)]. Moreover, rats in the CCl4 (8W)+HUMSC (liver) group had significantly lower levels of serum glutamic oxaloacetic transaminase, glutamic pyruvate transaminase, alpha-smooth muscle actin, and transforming growth factor-beta1 in the liver, whereas the expression of hepatic mesenchymal epithelial transition factor-phosphorylated type (Met-P) and hepatocyte growth factor was up-regulated, in comparison with the CCl4 (8W) group. Notably, engrafted HUMSCs scattered mostly in the hepatic connective tissue but did not differentiate into hepatocytes expressing human albumin or alpha-fetoprotein. Instead, these engrafted, undifferentiated HUMSCs secreted a variety of bioactive cytokines that may restore liver function and promote regeneration. Human cytokine assay revealed that the amounts of human cutaneous T cell-attracting chemokine, leukemia inhibitory factor, and prolactin were substantially greater in the livers of the CCl4 (8W)+HUMSC (liver) group, with considerably reduced hepatic inflammation manifested by a micro positron emission tomography scan. Our findings suggest that xenogeneic transplantation of HUMSCs is a novel approach for treating liver fibrosis and may be a promising therapeutic intervention in the future.
authors.affiliation: Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Tsai
authors.forename: Tz-Win
authors.initials: TW
authors.lastname: Fu
authors.forename: Yi-Ming Arthur
authors.initials: YM
authors.lastname: Chen
authors.forename: Tsui-Ling
authors.initials: TL
authors.lastname: Ko
authors.forename: Tien-Hua
authors.initials: TH
authors.lastname: Chen
authors.forename: Yang-Hsin
authors.initials: YH
authors.lastname: Shih
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hung
authors.forename: Yu-Show
authors.initials: YS
authors.lastname: Fu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D002454:Cell Differentiation; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000601:surgery; D054425:Chemokine CCL27 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008115:Liver Regeneration; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism
chemical_list: C492276:CCL27 protein, human; D054425:Chemokine CCL27; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D011388:Prolactin; D003094:Collagen; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase