Combined Cell Therapy for Ischemic Cardiomyopathy
Are two types of cells better than one for improving myocardial function after myocardial infarction (MI)?
Three months after ischemic injury, minipigs were injected transendocardially with mesenchymal stem cells (MSCs) alone or in combination with cardiac stem cells (CSCs), or vehicle. Cardiac magnetic resonance (CMR) imaging was performed at baseline and pre- and post-therapy.
Compared to placebo, pigs receiving cell treatment exhibited reduced scar size (MSCs: -44.1 ± 6.8%; CSCs/MSCs: -37.2 ± 5.4%; placebo: -12 ± 4.2%; p < 0.0001) and improved wall motion 3 months following treatment. However, significant improvements in ejection fraction (EF) only occurred in pigs receiving combined cell therapy (+6.9 ± 2.8 compared to +2.5 ± 1.6 EF units in placebo-treated animals; p = 0.0009). This was associated with increased cardiomyocyte mitotic activity.
The authors concluded that interactions between MSCs and CSCs enhance cardiac performance more than MSCs alone.
Although multiple cell replacement strategies for ischemic myocardial dysfunction have been tested, the optimal strategy remains to be determined. Preclinical and some clinical trials of ischemic heart disease have demonstrated efficacy with MSC treatment. This group recently demonstrated that combination treatment with CSCs and MSCs 2 weeks post-infarct is more efficacious than either treatment alone. This study confirms and extends the preclinical utility of this approach in a chronic ischemic model. This work provides impetus for further refinement of cell therapy strategies to improve ischemic myocardial dysfunction.
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