An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes.
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 10(5) 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.
Terai
Shuji
S
Department of Molecular Science & Applied Medicine (Gastroenterology & Hepatology), Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755-8505. terais@yamaguchi-u.ac.jp
Sakaida
Isao
I
Yamamoto
Naoki
N
Omori
Kaoru
K
Watanabe
Tomomi
T
Ohata
Shinya
S
Katada
Toshiaki
T
Miyamoto
Koji
K
Shinoda
Koh
K
Nishina
Hiroshi
H
Okita
Kiwamu
K
D000418:Albumins / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D005355:Fibrosis; D049452:Green Fluorescent Proteins; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D013997:Time Factors
D000418:Albumins; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D002251:Carbon Tetrachloride