title: Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells.
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, 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.
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Hida
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Miyoshi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kira
authors.forename: Kaoru
authors.initials: K
authors.lastname: Segawa
authors.forename: Taro
authors.initials: T
authors.lastname: Uyama
authors.forename: Taisuke
authors.initials: T
authors.lastname: Mori
authors.forename: Kenji
authors.initials: K
authors.lastname: Miyado
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Ikegami
authors.forename: ChangHao
authors.initials: C
authors.lastname: Cui
authors.forename: Tohru
authors.initials: T
authors.lastname: Kiyono
authors.forename: Satoru
authors.initials: S
authors.lastname: Kyo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
mesh_terms: D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods*; D018920:Coculture Techniques; D005260:Female; D006321:Heart / Q000502:physiology; D006801:Humans; D008297:Male; D008598:Menstruation / Q000097:blood*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells / Q000166:cytology