title: Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia.
abstract: Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC) transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP)-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion.
authors.affiliation: Department of Cardiovascular Surgery, Graduate School of Medicine, The University of Tokyo , Tokyo, Japan ; Equally contributed to the study.
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Research Team for Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology , Tokyo, Japan ; Equally contributed to the study.
authors.forename: M
authors.initials: M
authors.lastname: Toyoda
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine , Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Gojo
authors.affiliation: Research Team for Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology , Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Itakura
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine , Kyoto, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Kami
authors.affiliation: Department of Cardiology, Keio University School of Medicine , Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Miyoshi
authors.affiliation: Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, The University of Tokyo , Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kyo
authors.affiliation: Department of Cardiovascular Surgery, Graduate School of Medicine, The University of Tokyo , Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Reproductive Biology, National Research Institute for Child Health and Development , Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Umezawa
keywords: Allogeneic cell transplantation; Amniotic membrane; Chronic myocardial ischemia; Mesenchymal stromal cell; Porcine model