Direct Evaluation of Myocardial Viability and Stem Cell Engraftment Demonstrates Salvage of the Injured Myocardium. Issue 7 (27th March 2015)

• Record Type: Journal Article
• Authors: Kim, Paul J.; Mahmoudi, Morteza; Ge, Xiaohu; Matsuura, Yuka; Toma, Ildiko; Metzler, Scott; Kooreman, Nigel G.; Ramunas, John; Holbrook, Colin; McConnell, Michael V.; Blau, Helen; Harnish, Phillip; Rulifson, Eric; Yang, Phillip C.
• Is Part Of: Circulation research. Volume 116:Issue 7(2015)
• Publication Date: 2015-03-27
• Subjects: Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.116.304668
• Languages: English
• ISSNs: 0009-7330

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title> <underline>Rationale:</underline> </title> <p>The mechanism of functional restoration by stem cell therapy remains poorly understood. Novel manganese-enhanced MRI and bioluminescence reporter gene imaging were applied to follow myocardial viability and cell engraftment, respectively. Human-placenta–derived amniotic mesenchymal stem cells (AMCs) demonstrate unique immunoregulatory and precardiac properties. In this study, the restorative effects of 3 AMC-derived subpopulations were examined in a murine myocardial injury model: (1) unselected AMCs, (2) ckit<sup>+</sup>AMCs, and (3) AMC-derived induced pluripotent stem cells (MiPSCs).</p> </sec> <sec> <title> <underline>Objective:</underline> </title> <p>To determine the differential restorative effects of the AMC-derived subpopulations in the murine myocardial injury model using multimodality imaging.</p> </sec> <sec> <title> <underline>Methods and Results:</underline> </title> <p>SCID (severe combined immunodeficiency) mice underwent left anterior descending artery ligation and were divided into 4 treatment arms: (1) normal saline control (n=14), (2) unselected AMCs (n=10), (3) ckit<sup>+</sup>AMCs (n=13), and (4) MiPSCs (n=11). Cardiac MRI assessed myocardial viability and left ventricular function, whereas bioluminescence imaging assessed stem cell engraftment during a 4-week period. Immunohistological labeling and reverse transcriptase polymerase chain reaction of the explanted myocardium were performed. The unselected AMC and ckit<sup>+</sup>AMC–treated mice demonstrated transient left ventricular functional improvement. However, the MiPSCs exhibited a significantly greater increase in left ventricular function compared with all the other groups during the entire 4-week period. Left ventricular functional improvement correlated with increased myocardial viability and sustained stem cell engraftment. The MiPSC-treated animals lacked any evidence of de novo cardiac differentiation.</p> </sec> <sec> <title> <underline>Conclusion:</underline> </title> <p>The functional restoration seen in MiPSCs was characterized by increased myocardial viability and sustained engraftment without de novo cardiac differentiation, indicating salvage of the injured myocardium.</p> </sec> </abstract>