The therapeutic potential of human umbilical mesenchymal stem cells from Wharton's jelly in the treatment of rat liver fibrosis.
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.
Tsai
Pei-Chun
PC
Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Fu
Tz-Win
TW
Chen
Yi-Ming Arthur
YM
Ko
Tsui-Ling
TL
Chen
Tien-Hua
TH
Shih
Yang-Hsin
YH
Hung
Shih-Chieh
SC
Fu
Yu-Show
YS
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
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