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

Authors

  • Pei-Chun Tsai,

    1. Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China
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  • Tz-Win Fu,

    1. Department of Laboratory Medicine Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
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  • Yi-Ming Arthur Chen,

    1. Institute of Microbiology and Immunology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China
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  • Tsui-Ling Ko,

    1. Department of Anatomy, School of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China
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  • Tien-Hua Chen,

    1. Department of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China
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  • Yang-Hsin Shih,

    1. Department of Neurosurgery, Neurological Institute Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
    2. School of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China
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  • Shih-Chieh Hung,

    Corresponding author
    1. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China
    2. Stem Cell Laboratory, Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
    • Stem Cell Laboratory, Medical Research and Education, Veterans General Hospital, 201 Shih-Pai Road, Section 2, Taipei, Taiwan 11217, Republic of China
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    • These authors contributed equally to this study.

    • Telephone: +886-2-28757396; FAX: +886-2-28757396

  • Yu-Show Fu

    Corresponding author
    1. Department of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China
    2. Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, Republic of China
    • Department of Anatomy, School of Medicine, National Yang-Ming University, 155 Li-Nung Street, Section 2, Taipei, Taiwan 112, Republic of China
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    • These authors contributed equally to this study.

    • Telephone: 011-886-2-28267254; FAX: 011-886-2-28212884


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, 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 CCl4 (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 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. Liver Transpl 15:484–495, 2009. © 2009 AASLD.

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