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The therapeutic potential of human umbilical mesenchymal stem cells from Wharton's jelly in the treatment of rat liver fibrosis
Author(s) -
Tsai PeiChun,
Fu TzWin,
Chen YiMing Arthur,
Ko TsuiLing,
Chen TienHua,
Shih YangHsin,
Hung ShihChieh,
Fu YuShow
Publication year - 2009
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21715
Subject(s) - ccl4 , mesenchymal stem cell , wharton's jelly , hepatocyte growth factor , hepatic fibrosis , liver regeneration , stem cell , transplantation , sirius red , medicine , fibrosis , chemistry , pathology , regeneration (biology) , biology , carbon tetrachloride , microbiology and biotechnology , receptor , organic chemistry
We investigated the effect of human umbilical mesenchymal stem cells (HUMSCs) from Wharton's jelly on carbon tetrachloride (CCl 4 )–induced liver fibrosis in rats. Rats were treated with CCl 4 for 4 weeks, and this was followed by a direct injection of HUMSCs into their livers. After 4 more weeks of CCl 4 treatment (8 weeks in all), rats with HUMSC transplants [CCl 4 (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 CCl 4 for 8 weeks without HUMSC transplants [CCl 4 (8W)]. Moreover, rats in the CCl 4 (8W)+HUMSC (liver) group had significantly lower levels of serum glutamic oxaloacetic transaminase, glutamic pyruvate transaminase, α‐smooth muscle actin, and transforming growth factor‐β1 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 CCl 4 (8W) group. Notably, engrafted HUMSCs scattered mostly in the hepatic connective tissue but did not differentiate into hepatocytes expressing human albumin or α‐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 CCl 4 (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. Liver Transpl 15:484–495, 2009. © 2009 AASLD.