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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1830.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Therapeutic Potential of Unrestricted Somatic Stem Cells Isolated from Placental Cord Blood for Cardiac Repair Post Myocardial Infarction

Hiroto Iwasaki; Atsuhiko Kawamoto; Christina Willwerth; Miki Horii; Akira Oyamada; Hiroshi Akimaru; Toshihiko Shibata; Hidekazu Hirai; Shigefumi Suehiro; Stephan Wnendt; William L. Fodor; Takayuki Asahara

From Stem Cell Translational Research (H.I., A.K., M.H., A.O., H.A., T.A.), Institute of Biomedical Research and Innovation/RIKEN Center for Developmental Biology, Kobe, Japan; the Department of Cardiovascular Surgery (H.I., T.S., H.H., S.S.), Osaka City University Graduate School of Medicine, Japan; ViaCell Inc (C.W., S.W., W.L.F.), Cambridge, Mass; and the Department of Regenerative Medicine Science (T.A.), Tokai University School of Medicine, Isehara, Japan.

Correspondence to Takayuki Asahara, MD, Stem Cell Translational Research, Institute of Biomedical Research and Innovation/RIKEN Center for Developmental Biology, 2-2 Minatojima-Minamimachi, Chuo-Ku, Kobe 650-0047, Japan. E-mail asa777{at}is.icc.u-tokai.ac.jp

Objective— Unrestricted somatic stem cells (USSCs) were successfully identified from human cord blood. However, the efficacy of USSC transplantation for improving left ventricular (LV) function post myocardial infarction (MI) is still controversial.

Methods and Results— PBS, 1x10⁶ human fibroblasts (Fbr), 1x10⁵ USSCs (LD), or 1x10⁶ USSCs (HD) were transplanted intramyocardially 20 minutes after ligating the LAD of nude rats. Echocardiography and a microtip conductance catheter at day 28 revealed a dose-dependent improvement of LV function after USSC transplantation. Necropsy examination revealed dose-dependent augmentation of capillary density and inhibition of LV fibrosis. Dual-label immunohistochemistry for cardiac troponin-I and human nuclear antigen (HNA) demonstrated that human cardiomyocytes (CMCs) were dose-dependently generated in ischemic myocardium 28 days after USSC transplantation. Similarly, dual-label immunostaining for smooth muscle actin and class I human leukocyte antigen or that for von Willebrand factor and HNA also revealed a dose-dependent vasculogenesis after USSC transplantation. RT-PCR indicated that expression of human-specific genes of CMCs, smooth muscle cells, and endothelial cell markers in infarcted myocardium were significantly augmented in USSC-treated animals compared with control groups.

Conclusions— USSC transplantation leads to functional improvement and recovery from MI and exhibits a significant and dose-dependent potential for concurrent cardiomyogenesis and vasculogenesis.

USSCs can be expanded up to 10¹⁵ cells without losing pluripotency in culture. The USSC therapy resulted in dose-dependent enhancement of neovascularization, inhibition of LV remodeling, and improvement of LV function post MI. USSCs could be used as a highly valuable resource for cellular cardiomyoplasty in the future clinical application.

Key Words: USSC • cardiomyogenesis • vasculogenesis • cell therapy • myocardial infarction