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TISSUE-SPECIFIC STEM CELLS

Isolation of a Bone Marrow-Derived Stem Cell Line with High Proliferation Potential and Its Application for Preventing Acute Fatal Liver Failure

^aDepartment of Cell Biology,
^bDepartment of Gastroenterology and Hepatology, and
^cDepartment of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho, Okayama, Japan;
^dDepartment of Food and Nutrition, Faculty of Human Services, Okayama Gakuin University, Aruki, Kurashiki, Japan;
^eDepartment of Biochemistry, Medical Faculty of Hasanuddin University, Makassar, South Sulawesi, Indonesia

Key Words. Rat bone marrow • Clonal stem cell lines • Hepatocyte-like cells • Mass production • Intrasplenic transplantation

Correspondence: Nam-ho Huh, M.D., Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Schikata-cho, Okayama 700-8558, Japan. Telephone: (81)-86-235-7393; Fax: (81)-86-235-7400; e-mail: namu{at}md.okayama-u.ac.jp

Received on February 7, 2007; accepted for publication on July 31, 2007.

First published online in STEM CELLS EXPRESS  August 16, 2007.


Transplantation of hepatocytes or hepatocyte-like cells of extrahepatic origin is a promising strategy for treatment of acute and chronic liver failure. We examined possible utility of hepatocyte-like cells induced from bone marrow cells for such a purpose. Clonal cell lines were established from the bone marrow of two different rat strains. One of these cell lines, rBM25/S3 cells, grew rapidly (doubling time, 24 hours) without any appreciable changes in cell properties for at least 300 population doubling levels over a period of 300 days, keeping normal diploid karyotype. The cells expressed CD29, CD44, CD49b, CD90, vimentin, and fibronectin but not CD45, indicating that they are of mesenchymal cell origin. When plated on Matrigel with hepatocyte growth factor and fibroblast growth factor-4, the cells efficiently differentiated into hepatocyte-like cells that expressed albumin, cytochrome P450 (CYP) 1A1, CYP1A2, glucose 6-phosphatase, tryptophane-2,3-dioxygenase, tyrosine aminotransferase, hepatocyte nuclear factor (HNF)1, and HNF4. Intrasplenic transplantation of the differentiated cells prevented fatal liver failure in 90%-hepatectomized rats. In conclusion, a clonal stem cell line derived from adult rat bone marrow could differentiate into hepatocyte-like cells, and transplantation of the differentiated cells could prevent fatal liver failure in 90%-hepatectomized rats. The present results indicate a promising strategy for treating human fatal liver diseases.

Disclosure of potential conflicts of interest is found at the end of this article.

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