Direct Evaluation of Myocardial Viability and Stem Cell Engraftment Demonstrates Salvage of the Injured Myocardium
Rationale: The mechanism of functional restoration by stem cell therapy remains poorly under-stood. Novel manganese-enhanced MRI and bioluminescence reporter gene imaging (BLI) were applied to follow myocardial viability and cell engraftment, respectively. Human-placenta-derived amniotic mesenchymal stem cells (AMCs) demonstrate unique immunoregulatory and pre-cardiac properties. In this study, the restorative effects of three AMC-derived sub-populations were exam-ined in a murine myocardial injury model: 1) unselected AMCs (uAMCs), 2) ckit+AMCs (c+AMCs), and 3) AMC-derived iPSCs (MiPSCs).
Objective: Determine the differential restorative effects of the AMC-derived sub-populations in the murine myocardial injury model using multi-modality imaging.
Methods and Results: SCID mice underwent left anterior descending artery ligation and were divid-ed into 4 treatment arms: 1) normal saline control (n=14), 2) uAMCs (n=10), 3) c+AMCs (n=13), and 4) MiPSCs (n=11). Cardiac MRI assessed myocardial viability and left ventricular (LV) func-tion while BLI assessed stem cell engraftment over a four-week period. Immunohistological label-ing and RT-PCR of the explanted myocardium were performed. The uAMC and c+AMC treated mice demonstrated transient LV functional improvement. However, the MiPSCs exhibited a signifi-cantly greater increase in LV function compared to all the other groups during the entire four-week period. LV functional improvement correlated with increased myocardial viability and sustained stem cell engraftment. The MiPSCs treated animals lacked any evidence of de novo cardiac differ-entiation.
Conclusions: 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.
- amniotic mesenchymal stem cells
- manganese-enhanced MRI
- stem cell imaging
- cardiac magnetic resonance imaging
- stem cell
- ischemic heart disease
- acute myocardial infarction
- Received June 24, 2014.
- Revision received January 3, 2015.
- Accepted February 4, 2015.