The therapeutic potential of human umbilical mesenchymal stem cells from Wharton's jelly in the treatment of rat liver fibrosis

✍ Scribed by Pei-Chun Tsai; Tz-Win Fu; Yi-Ming Arthur Chen; Tsui-Ling Ko; Tien-Hua Chen; Yang-Hsin Shih; Shih-Chieh Hung; Yu-Show Fu

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 513 KB
• Volume: 15
• Category: Article
• ISSN: 1527-6465
• DOI: 10.1002/lt.21715

✦ Synopsis

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)ϩHUMSC 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)ϩHUMSC (liver) group had significantly lower levels of serum glutamic oxaloacetic transaminase, glutamic pyruvate transaminase, ␣-smooth muscle actin, and transforming growth factor-␤1 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 ␣-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)ϩHUMSC (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.