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Blood, 15 July 2005, Vol. 106, No. 2, pp. 756-763. Prepublished online as a Blood First Edition Paper on April 7, 2005; DOI 10.1182/blood-2005-02-0572. This Article Full Text (PDF) All Versions of this Article: 2005-02-0572v1 106/2/756    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sato, Y. Articles by Niitsu, Y. Search for Related Content PubMed PubMed Citation Articles by Sato, Y. Articles by Niitsu, Y. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 10, 2005 Accepted March 16, 2005 Human mesenchymal stem cells xenografted directly to rat liver differentiated into human hepatocytes without fusion Yasushi Sato, Hironobu Araki, Junji Kato, Kiminori Nakamura, Yutaka Kawano, Masayoshi Kobune, Tsutomu Sato, Koji Miyanishi, Tetsuji Takayama, Minoru Takahashi, Rishu Takimoto, Satoshi Iyama, Takuya Matsunaga, Seiji Ohtani, Akihiro Matsuura, Hirofumi Hamada, and Yoshiro Niitsu* Fourth Department of Internal Medicine, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido, Japan Department of Molecular Medicine, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido, Japan Department of Biomedical Engineering, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido, Japan Department of Pathology, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan * Corresponding author; email: niitsu{at}sapmed.ac.jp. Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34+cells and non MSCs/CD34- cells and examined them by directly xenografting to allylalcohol(AA) treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18) and asialoglycoprotein receptor (AGPR), and by RT-PCR for expression of AFP and Alb mRNA, were observed only in recipient liver with MSCs fraction. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by FISH. The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the Alb gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat liver. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H Aurich, M Sgodda, P Kaltwasser, M Vetter, A Weise, T Liehr, M Brulport, J G Hengstler, M M Dollinger, W E Fleig, et al. Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo Gut, April 1, 2009; 58(4): 570 - 581. [Abstract] [Full Text] [PDF] Y. Kamada, Y. Yoshida, Y. Saji, J. Fukushima, S. Tamura, S. Kiso, and N. 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