Objective: Previous regenerative studies have demonstrated massive cell losses after intramyocardial cellular delivery. Therefore, efforts at reducing mechanical losses may prove more successful in optimising cellular therapy. In this study, we hypothesized that escalating mesenchymal stem cells (MSCs) dose will not produce corresponding improvement in cardiac function due to washout of the small cells in microcirculation. Using microspheres similar in size to MSCs, that are encapsulated in alginate-poly-l-lysine-alginate (APA), we tested the hypothesis that size is an important factor in early losses. Methods: In experiment I, five groups of rats (n=9 each) underwent coronary ligation; group I had no treatment; the other groups received escalating 0.5×106, 1.5×106, 3×106 and 5×106 of MSCs each. Echocardiogram was performed at baseline, 2 days and 7 weeks after surgery. In experiment II, cell-sized microspheres (10μm) were encapsulated in APA microcapsules. In group I (n=16), rats received bare microspheres, group II (n=16) microspheres within 200μm microcapsules and in group III (n=16), microspheres within 400μm microcapsules. After 20min, hearts were quantified for the amount retained. Results: Myocardial function did not improve further with escalating cell doses beyond an initial response at 1.5×106 cells. Encapsulated microspheres in 200μm and 400μm microcapsules demonstrated a fourfold increase in retention rate compared with 10μm microspheres. Conclusion: We concluded that suboptimal functional improvement in this animal model starts at 1.5×106 cells and does not respond to escalating cell doses. Improving mechanical retention is possible by increasing the size of the injectate. Microencapsulation could be used to encapsulate donor cells and facilitate functional improvement in cellular heart failure therapy.
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