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INTRODUCTION: IFATS COLLECTION: TISSUE-SPECIFIC STEM CELLS

IFATS Collection: In Vivo Therapeutic Potential of Human Adipose Tissue Mesenchymal Stem Cells After Transplantation into Mice with Liver Injury

^aSection for Studies on Metastasis, National Cancer Center Research Institute, Tokyo, Japan;
^bDepartment of Biology, School of Education, Waseda University, Tokyo, Japan;
^cDepartment of Surgery, International Medical Center of Japan, Tokyo, Japan;
^dDepartment of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Tottori, Japan

Key Words. Adipose • Mesenchymal stem cells • Liver regeneration • Liver function

Correspondence: Correspondence: Takahiro Ochiya, Ph.D.,Head of Section for Studies on Metastasis, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. Telephone: 81-3-3542-2511, ext. 4452; Fax: 81-3-3541-2685; e-mail: tochiya{at}ncc.go.jp

Received on January 11, 2008; accepted for publication on May 27, 2008.

First published online in STEM CELLS EXPRESS  June 5, 2008.

Mesenchymal stem cells (MSCs), largely present in the adult human body, represent an attractive tool for the establishment of a stem cell-based therapy for liver diseases. Recently, the therapeutic potential and immunomodulatory activity of MSCs have been revealed. Adipose tissue-derived mesenchymal stem cells (AT-MSCs), so-called adipose-derived stem cells or adipose stromal cells, because of their high accessibility with minimal invasiveness, are especially attractive in the context of future clinical applications. The goal of the present study was to evaluate the therapeutic potential of AT-MSCs by their transplantation into nude mice with CCl₄-caused liver injury. We observed that after transplantation, AT-MSCs can improve liver functions, which we verified by changes in the levels of biochemical parameters. Ammonia, uric acid, glutamic-pyruvic transaminase, and glutamic-oxaloacetic transaminase concentrations returned to a nearly normal level after AT-MSC transplantation. These results raised the question of how AT-MSCs can achieve this. To discover the possible mechanisms involved in this therapeutic ability of AT-MSCs, in vitro production of cytokines and growth factors was analyzed and compared with MSCs from bone marrow (BM-MSCs) and normal human dermal fibroblasts (NHDFs). As a result we observed that AT-MSCs secrete interleukin 1 receptor (IL-1R), IL-6, IL-8, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein 1, nerve growth factor, and hepatocyte growth factor in a volume higher than both BM-MSCs and NHDFs. Thus, our findings suggest that AT-MSCs may account for their broad therapeutic efficacy in animal models of liver diseases and in the clinical settings for liver disease treatment.

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