Abstract
Aim: One of the main limitations for an effective cell therapy for the heart is the poor cell engraftment after implantation, which is partly due to a large percentage of cell death in the hostile myocardium. In the present study, we investigated the utilization of Necrostatin-1 (Nec-1) as a possible attenuator of cell death in Sca-1+ cardiac progenitor cells (CPCs). Methods and Results: Under oxidative stress conditions in vitro, Nec-1 pretreatment reduced necrotic cell death in Sca-1+ CPCs. In a mouse model of myocardial infarction, survival of CPCs 3 days after intra-myocardial injection was 39% higher (BLI signal, 71,665 ± 11,165 vs 117,138 ± 18,567 ph/s/cm2/sr) in cells pretreated with the Nec-1 compound. However, the increase in cell number did not translate into improved cardiac function at one month follow-up (EF %, 20.6±2.1 vs 21.4±2.5 for vehicle and Nec-1 treated CPC, respectively). We extensively investigated, but did not find, alternative effects to the pro-survival properties of the compound on the CPCs. Furthermore, CPCs rescued by Nec-1 remained functionally competent. Conclusion: A pharmacological pretreatment approach to solely enhance cell survival on the short-term does not seem to be effective strategy to improve cardiac cell therapy with Sca-1+ CPCs. Since the initial cell retention directly after injection is low (~10%), survival strategies could conceivably be more useful in a tissue engineering setting, in which they can exert their effects on larger number of cells.
Published Version
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