Abstract
Mesenchymal stem cells (MSC) have emerged as a potential stem cell type for cardiac regeneration after myocardial infarction (MI). Recently, we isolated and characterized mesenchymal stem cells derived from rat fetal heart (fC-MSC), which exhibited potential to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. In the present study, we investigated the therapeutic efficacy of intravenously injected fC-MSC in a rat model of MI using multi-pinhole gated SPECT-CT system. fC-MSC were isolated from the hearts of Sprague Dawley (SD) rat fetuses at gestation day 16 and expanded ex vivo. One week after induction of MI, 2×106 fC-MSC labeled with PKH26 dye (n = 6) or saline alone (n = 6) were injected through the tail vein of the rats. Initial in vivo tracking of 99mTc-labeled fC-MSC revealed a focal uptake of cells in the anterior mid-ventricular region of the heart. At 4 weeks of fC-MSC administration, the cells labeled with PKH26 were located in abundance in infarct/peri-infarct region and the fC-MSC treated hearts showed a significant increase in left ventricular ejection fraction and a significant decrease in the end diastolic volume, end systolic volume and left ventricular myo-mass in comparison to the saline treated group. In addition, fC-MSC treated hearts had a significantly better myocardial perfusion and attenuation in the infarct size, in comparison to the saline treated hearts. The engrafted PKH26-fC-MSC expressed cardiac troponin T, endothelial CD31 and smooth muscle sm-MHC, suggesting their differentiation into all major cells of cardiovascular lineage. The fC-MSC treated hearts demonstrated an up-regulation of cardio-protective growth factors, anti-fibrotic and anti-apoptotic molecules, highlighting that the observed left ventricular functional recovery may be due to secretion of paracrine factors by fC-MSC. Taken together, our results suggest that fC-MSC therapy may be a new therapeutic strategy for MI and multi-pinhole gated SPECT-CT system may be a useful tool to evaluate cardiac perfusion, function and cell tracking after stem cell therapy in acute myocardial injury setting.
Highlights
Cellular cardiomyoplasty has emerged as a potential therapeutic strategy for patients with acute myocardial infarction (MI)
One week after MI, no significant differences in the ejection fraction (EF), end diastolic volume (EDV), end systolic volume (ESV) and left ventricular (LV) myo-mass were observed between saline and fC-Mesenchymal stem cells (MSC) treated hearts (Table 2 and Fig. 2)
We have demonstrated a significant improvement in the cardiac functions following fetal cardiac mesenchymal stem cells (fC-MSC) therapy in a rat model of MI using the multi-pinhole SPECT/CT technology
Summary
Cellular cardiomyoplasty has emerged as a potential therapeutic strategy for patients with acute myocardial infarction (MI). It has been shown that tissue specific MSC possess unique properties with inherent potential of differentiation in to cell lineages of their tissue of origin [13] In this context, we recently isolated and characterized MSC derived from rat fetal heart and described these cells as fetal cardiac mesenchymal stem cells (fC-MSC). We recently isolated and characterized MSC derived from rat fetal heart and described these cells as fetal cardiac mesenchymal stem cells (fC-MSC) They exhibited the potential to differentiate in to cardiomyocytes, endothelial cells and smooth muscle cells over successive passages, while maintaining expression of TERT and a normal karyotype [14]
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