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

¹ Department of Cardiology, Keio University School of Medicine, Tokyo,160-8582, JAPAN; Department of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, Tokyo,157-8535, JAPAN; Department of Pathology, Keio University School of Medicine, Tokyo,160-8582, JAPAN
² Department of Cardiology, Keio University School of Medicine, Tokyo,160-8582, JAPAN; Department of Pathology, Keio University School of Medicine, Tokyo,160-8582, JAPAN
³ Department of Cardiology, Keio University School of Medicine, Tokyo,160-8582, JAPAN; Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine, Tokyo,160-8582, JAPAN
⁴ Department of Cardiology, Keio University School of Medicine, Tokyo,160-8582, JAPAN
⁵ Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo,160-8582, JAPAN
⁶ Department of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, Tokyo,157-8535, JAPAN
⁷ Department of Pathology, Keio University School of Medicine, Tokyo,160-8582, JAPAN
⁸ Department of Cardiology, Keio University School of Medicine, Tokyo,160-8582, JAPAN; Department of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, Tokyo,157-8535, JAPAN
⁹ Virology Division, National Cancer Center Research Institute, Tokyo,104-0045, JAPAN
¹⁰ Department of Obstetrics and Gynecology, Kanazawa University, School of Medicine, Kanazawa,920-0293, JAPAN
¹¹ Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo,162-8666, JAPAN

^* To whom correspondence should be addressed. E-mail: smiyoshi{at}cpnet.med.keio.ac.jp.

	Abstract

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, non-invasive 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 being 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.