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Repair of the injured adult heart involves new myocytes potentially derived from resident cardiac stem cells.

ABSTRACT: The ability of the adult heart to generate new myocytes after injury is not established.Our purpose was to determine whether the adult heart has the capacity to generate new myocytes after injury, and to gain insight into their source.Cardiac injury was induced in the adult feline heart by infusing isoproterenol (ISO) for 10 days via minipumps, and then animals were allowed to recover for 7 or 28 days. Cardiac function was measured with echocardiography, and proliferative cells were identified by nuclear incorporation of 5-bromodeoxyuridine (BrdU; 7-day minipump infusion). BrdU was infused for 7 days before euthanasia at days 10, 17, and 38 or during injury and animals euthanized at day 38. ISO caused reduction in cardiac function with evidence of myocyte loss from necrosis. During this injury phase there was a significant increase in the number of proliferative cells in the atria and ventricle, but there was no increase in BrdU+ myocytes. cKit+ cardiac progenitor cells were BrdU labeled during injury. During the first 7 days of recovery there was a significant reduction in cellular proliferation (BrdU incorporation) but a significant increase in BrdU+ myocytes. There was modest improvement in cardiac structure and function during recovery. At day 38, overall cell proliferation was not different than control, but increased numbers of BrdU+ myocytes were found when BrdU was infused during injury.These studies suggest that ISO injury activates cardiac progenitor cells that can differentiate into new myocytes during cardiac repair.

SUBMITTER: Angert D

PROVIDER: S-EPMC3322670 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Repair of the injured adult heart involves new myocytes potentially derived from resident cardiac stem cells.

Angert David D Berretta Remus M RM Kubo Hajime H Zhang Hongyu H Chen Xiongwen X Wang Wei W Ogorek Barbara B Barbe Mary M Houser Steven R SR

Circulation research 20110331 10

<h4>Rationale</h4>The ability of the adult heart to generate new myocytes after injury is not established.<h4>Objective</h4>Our purpose was to determine whether the adult heart has the capacity to generate new myocytes after injury, and to gain insight into their source.<h4>Methods and results</h4>Cardiac injury was induced in the adult feline heart by infusing isoproterenol (ISO) for 10 days via minipumps, and then animals were allowed to recover for 7 or 28 days. Cardiac function was measured ...[more]

PMID: 21454756

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Project description:Cardiac myocytes derived from pluripotent stem cells have demonstrated the potential to mitigate damage of the infarcted myocardium and improve left ventricular ejection fraction. However, the mechanism underlying the functional benefit is unclear.To evaluate whether the transplantation of cardiac-lineage differentiated derivatives enhance myocardial viability and restore left ventricular ejection fraction more effectively than undifferentiated pluripotent stem cells after a myocardial injury. Herein, we utilize novel multimodality evaluation of human embryonic stem cells (hESCs), hESC-derived cardiac myocytes (hCMs), human induced pluripotent stem cells (iPSCs), and iPSC-derived cardiac myocytes (iCMs) in a murine myocardial injury model.Permanent ligation of the left anterior descending coronary artery was induced in immunosuppressed mice. Intramyocardial injection was performed with (1) hESCs (n=9), (2) iPSCs (n=8), (3) hCMs (n=9), (4) iCMs (n=14), and (5) PBS control (n=10). Left ventricular ejection fraction and myocardial viability, measured by cardiac magnetic resonance imaging and manganese-enhanced magnetic resonance imaging, respectively, was significantly improved in hCM- and iCM-treated mice compared with pluripotent stem cell- or control-treated mice. Bioluminescence imaging revealed limited cell engraftment in all treated groups, suggesting that the cell secretions may underlie the repair mechanism. To determine the paracrine effects of the transplanted cells, cytokines from supernatants from all groups were assessed in vitro. Gene expression and immunohistochemistry analyses of the murine myocardium demonstrated significant upregulation of the promigratory, proangiogenic, and antiapoptotic targets in groups treated with cardiac lineage cells compared with pluripotent stem cell and control groups.This study demonstrates that the cardiac phenotype of hCMs and iCMs salvages the injured myocardium effectively than undifferentiated stem cells through their differential paracrine effects.

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Repair of the injured adult heart involves new myocytes potentially derived from resident cardiac stem cells.

Publications

Repair of the injured adult heart involves new myocytes potentially derived from resident cardiac stem cells.

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