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J. Biochem, 2003, Vol. 134, No. 4 551-558
© 2003 Japanese Biochemical Society

CELL

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

Shuji Terai*,1, Isao Sakaida1, Naoki Yamamoto1, Kaoru Omori1, Tomomi Watanabe2, Shinya Ohata2, Toshiaki Katada2, Koji Miyamoto3, Koh Shinoda4, Hiroshi Nishina2 and Kiwamu Okita1

1 Department of Molecular Science & Applied Medicine (Gastroenterology & Hepatology), Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755-8505; 2 Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033; 3 Department of Molecular Science & Applied Medicine (Bio-Regulation), Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755-8505; and 4 Departmemt of Neuro-anatomy & Neuroscience, Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755-8505

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 x 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.

* To whom correspondence should be addressed. Tel: +81-836-22-2241, Fax: +81-836-22-2240, E-mail: terais{at}yamaguchi-u.ac.jp


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