Non‐inferiority of microencapsulated mesenchymal stem cells to free cells in cardiac repair after myocardial infarction: A rationale for using paracrine factor(s) instead of cells

摘要

A major translational barrier to the use of stem cell ( )‐based therapy in patients with myocardial infarction ( ) is the lack of a clear understanding of the mechanism(s) underlying the cardioprotective effect of s. Numerous paracrine factors from s may account for reduction in infarct size, but myocardial salvage associated with transdifferentiation of s into vascular cells as well as cardiomyocyte‐like cells may be involved too. In this study, bone marrow‐derived rat mesenchymal ( s) were microencapsulated in alginate preventing viable cell release while supporting their secretory phenotype. The hypothesis on the key role of paracrine factors from s in their cardioprotective activity was tested by comparison of the effect of encapsulated vs free s in the rat model of . Intramyocardial administration of both free and encapsulated s after caused reduction in scar size (12.1 ± 6.83 and 14.7 ± 4.26%, respectively, vs 21.7 ± 6.88% in controls, = 0.015 and = 0.03 respectively). Scar size was not different in animals treated with free and encapsulated ( = 0.637). These data provide evidence that ‐derived growth factors and cytokines are crucial for cardioprotection elicited by . Administration of either free or encapsulated s was not arrhythmogenic in non‐infarcted rats. The consistency of our data with the results of other studies on the major role of secretome components in cardiac protection further support the theory that the use of live, though encapsulated, cells for therapy may be replaced with heart‐targeted‐sustained delivery of growth factors/cytokines.