An <i>In Vivo</i> Model for Monitoring <i>Trans</i>-Differentiation of Bone Marrow Cells into Functional Hepatocytes

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  • Terai Shuji
    Department of Molecular Science & Applied Medicine (Gastroenterology & Hepatology), Yamaguchi University School of Medicine
  • Sakaida Isao
    Department of Molecular Science & Applied Medicine (Gastroenterology & Hepatology), Yamaguchi University School of Medicine
  • Yamamoto Naoki
    Department of Molecular Science & Applied Medicine (Gastroenterology & Hepatology), Yamaguchi University School of Medicine
  • Omori Kaoru
    Department of Molecular Science & Applied Medicine (Gastroenterology & Hepatology), Yamaguchi University School of Medicine
  • Watanabe Tomomi
    Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo
  • Ohata Shinya
    Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo
  • Katada Toshiaki
    Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo
  • Miyamoto Koji
    Department of Molecular Science & Applied Medicine (Bio-Regulation), Yamaguchi University School of Medicine
  • Shinoda Koh
    Departmemt of Neuro-anatomy & Neuroscience, Yamaguchi University School of Medicine
  • Nishina Hiroshi
    Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo
  • Okita Kiwamu
    Department of Molecular Science & Applied Medicine (Gastroenterology & Hepatology), Yamaguchi University School of Medicine

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Other Title
  • An In Vivo Model for Monitoring Trans-Differentiation of Bone Marrow Cells into Functional Hepatocytes
  • In Vivo Model for Monitoring Trans Differentiation of Bone Marrow Cells into Functional Hepatocytes
  • An in vivo model for monitoring trans‐differentiation of bone marrow cells into functional hepatocytes

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Abstract

The plasticity of bone marrow cells (BMCs) remains controversial. The present study found that persistent injury induces efficient trans-differentiation of BMCs into functional hepatocytes. Mice with liver cirrhosis induced by carbon tetrachloride were injected with 1×105 non-treated green fluorescent protein (GFP)-positive BMCs via the tail vein. In these mice, transplanted GFP-positive BMCs efficiently migrated into the peri-portal area of liver lobules after one day, repopulating 25% of the recipient liver by 4 weeks. In contrast, no GFP-positive BMCs were detected following transplantation into control mice with undamaged livers. BMCs trans-differentiated into functional mature hepatocytes via immature hepatoblasts. Serum albumin levels were significantly elevated to compensate for chronic liver failure in BMC transplantation. These results reveal that recipient conditions and microenvironments represent key factors for successful cell therapy using BMCs.

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