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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2007-0826v1 26/7/1695    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Google Scholar Articles by Hida, N. Articles by Umezawa, A. PubMed PubMed Citation Articles by Hida, N. Articles by Umezawa, A.

TISSUE-SPECIFIC STEM CELLS

Novel Cardiac Precursor-Like Cells from Human Menstrual Blood-Derived Mesenchymal Cells

^aDepartment of Cardiology, Keio University School of Medicine, Tokyo, Japan;
^bDepartment of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, Tokyo, Japan;
^cDepartment of Pathology, Keio University School of Medicine, Tokyo, Japan;
^dInstitute for Advanced Cardiac Therapeutics, Keio University School of Medicine, Tokyo, Japan;
^eDepartment of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan;
^fVirology Division, National Cancer Center Research Institute, Tokyo, Japan;
^gDepartment of Obstetrics and Gynecology, Kanazawa University, School of Medicine, Kanazawa, Japan;
^hInstitute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan

Key Words. Cardiomyogenesis human mesenchymal stem cell • Menstrual blood endometrial gland • Cell sheet technology cardiac precursors

Correspondence: Shunichiro Miyoshi M.D., Ph.D., Keio University School of Medicine, 35-Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan. Telephone: +81-3-3353-1211 (ext 62310); Fax: +81-3-3353-2502; e-mail: smiyoshi{at}cpnet.med.keio.ac.jp

Received October 2, 2007; accepted for publication April 6, 2008.
First published online in STEM CELLS EXPRESS   April 17, 2008.

Stem cell therapy can help repair damaged heart tissue. Yet many of the suitable cells currently identified for human use are difficult to obtain and involve invasive procedures. In our search for novel stem cells with a higher cardiomyogenic potential than those available from bone marrow, we discovered that potent cardiac precursor-like cells can be harvested from human menstrual blood. This represents a new, noninvasive, and potent source of cardiac stem cell therapeutic material. We demonstrate that menstrual blood-derived mesenchymal cells (MMCs) began beating spontaneously after induction, exhibiting cardiomyocyte-specific action potentials. Cardiac troponin-I-positive cardiomyocytes accounted for 27%–32% of the MMCs in vitro. The MMCs proliferated, on average, 28 generations without affecting cardiomyogenic transdifferentiation ability, and expressed mRNA of GATA-4 before cardiomyogenic induction. Hypothesizing that the majority of cardiomyogenic cells in MMCs originated from detached uterine endometrial glands, we established monoclonal endometrial gland-derived mesenchymal cells (EMCs), 76%–97% of which transdifferentiated into cardiac cells in vitro. Both EMCs and MMCs were positive for CD29, CD105 and negative for CD34, CD45. EMCs engrafted onto a recipient's heart using a novel 3-dimensional EMC cell sheet manipulation transdifferentiated into cardiac tissue layer in vivo. Transplanted MMCs also significantly restored impaired cardiac function, decreasing the myocardial infarction (MI) area in the nude rat model, with tissue of MMC-derived cardiomyocytes observed in the MI area in vivo. Thus, MMCs appear to be a potential novel, easily accessible source of material for cardiac stem cell-based therapy.

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