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: 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
• Journal: Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society (Liver Transpl) Vol. 15 Issue 5 Pg. 484-95 (May 2009) ISSN: 1527-6473 [Electronic] United States
• PMID: 19399744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL27 protein, human
• Chemokine CCL27
• LIF protein, human
• Leukemia Inhibitory Factor
• Prolactin
• Collagen
• Carbon Tetrachloride
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Carbon Tetrachloride
• Cell Differentiation
• Cells, Cultured
• Chemical and Drug Induced Liver Injury (pathology, surgery)
• Chemokine CCL27 (metabolism)
• Collagen (metabolism)
• Disease Models, Animal
• Fibrosis (chemically induced, metabolism, pathology, surgery)
• Hepatic Stellate Cells (metabolism, pathology)
• Humans
• Leukemia Inhibitory Factor (metabolism)
• Liver (metabolism, pathology, surgery)
• Liver Regeneration
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (metabolism)
• Prolactin (metabolism)
• Rats
• Rats, Sprague-Dawley
• Severity of Illness Index
• Time Factors
• Umbilical Cord (cytology, metabolism)