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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 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 Citation Map 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. Related Collections Hematopoiesis and Stem Cells Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents TRANSPLANTATION Human mesenchymal stem cells xenografted directly to rat liver are 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 From the Fourth Department of Internal Medicine, Department of Molecular Medicine, and Department of Biomedical Engineering, Sapporo Medical University, School of Medicine, Sapporo, Japan; and Department of Pathology, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan. 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 reverse transcription-polymerase chain reaction (RT-PCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (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 albumin 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 livers. (Blood. 2005;106:756-763) 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. Hayashi Transplantation of basic fibroblast growth factor-pretreated adipose tissue-derived stromal cells enhances regression of liver fibrosis in mice Am J Physiol Gastrointest Liver Physiol, February 1, 2009; 296(2): G157 - G167. [Abstract] [Full Text] [PDF] N. Brezillon, D. Kremsdorf, and M. C. Weiss Cell therapy for the diseased liver: from stem cell biology to novel models for hepatotropic human pathogens Dis. Model. Mech., September 1, 2008; 1(2-3): 113 - 130. [Abstract] [Full Text] [PDF] Y. Hayashi, S. Tsuji, M. Tsujii, T. Nishida, S. Ishii, H. Iijima, T. Nakamura, H. Eguchi, E. Miyoshi, N. Hayashi, et al. Topical Implantation of Mesenchymal Stem Cells Has Beneficial Effects on Healing of Experimental Colitis in Rats J. Pharmacol. Exp. Ther., August 1, 2008; 326(2): 523 - 531. [Abstract] [Full Text] [PDF] Y. Hayashi, S. Tsuji, M. Tsujii, T. Nishida, S. Ishii, H. Iijima, T. Nakamura, H. Eguchi, E. Miyoshi, N. Hayashi, et al. Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G778 - G786. [Abstract] [Full Text] [PDF] M. Sasaki, R. Abe, Y. Fujita, S. Ando, D. Inokuma, and H. Shimizu Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type J. Immunol., February 15, 2008; 180(4): 2581 - 2587. [Abstract] [Full Text] [PDF] S. J Forbes Stem cell therapy for chronic liver disease choosing the right tools for the job Gut, February 1, 2008; 57(2): 153 - 155. [Full Text] [PDF] L V. di Bonzo, I Ferrero, C Cravanzola, K Mareschi, D Rustichell, E Novo, F Sanavio, S Cannito, E Zamara, M Bertero, et al. 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M Dollinger, W. Schormann, J. Walldorf, J. G Hengstler, W. E Fleig, et al. Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers Gut, March 1, 2007; 56(3): 405 - 415. [Abstract] [Full Text] [PDF] Z. Ilic, H. Leffert, and S. Sell Sequential Exposure to Cytokines Reflecting Embryogenesis: The Key for In Vitro Differentiation of Adult Bone Marrow Stem Cells into Functional Hepatocyte-Like Cells Toxicol. Sci., December 1, 2006; 94(2): 235 - 239. [Full Text] [PDF] L. d. S. Meirelles, P. C. Chagastelles, and N. B. Nardi Mesenchymal stem cells reside in virtually all post-natal organs and tissues J. Cell Sci., June 1, 2006; 119(11): 2204 - 2213. [Abstract] [Full Text] [PDF] F. Zeng, M.-j. Chen, D. A. Baldwin, Z.-j. Gong, J.-b. Yan, H. Qian, J. Wang, X. Jiang, Z.-r. Ren, D. Sun, et al. 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