Direct Evaluation of Myocardial Viability and Stem Cell Engraftment Demonstrates Salvage of the Injured Myocardium
2015
Rationale: 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+AMCs, and (3) AMC-derived induced pluripotent stem cells (MiPSCs).
Objective: To determine the differential restorative effects of the AMC-derived subpopulations in the murine myocardial injury model using multimodality imaging.
Methods and Results: 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+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+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.
Conclusion: 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.
# Novelty and Significance {#article-title-37}
Keywords:
- Stem-cell therapy
- Induced pluripotent stem cell
- Biology
- Stem cell
- Internal medicine
- Severe combined immunodeficiency
- Mesenchymal stem cell
- Myocardial infarction
- Cardiology
- Ligation
- Bioluminescence imaging
- Cancer research
- Molecular imaging
- Proto-Oncogene Proteins c-kit
- Reporter gene
- Surgery
- Magnetic resonance imaging
- Correction
- Source
- Cite
- Save
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