*Purpose: Cardiac progenitor cells (CPCs, c-kit⁺) are well-characterized stem cell type shown to potentiate cardiac regeneration in myocardial infarct (MI) model. However, auto and allo immune response to transplanted adult CPCs (aCPCs) reduces cell retention and MI recovery. We aimed to increase the regenerative potential of aCPCs by reducing immune response directed to the transplanted aCPCs using cyclosporine A (CSA).

*Methods: Adult CPCs isolated from Wister Kyoto rat was transplanted into Brown Norway MI rats. CSA were administered orally as immune suppressant. CSA alone and Iscove’s Modified Dulbecco’s Media (IMDM) were served as control groups. Echocardiogram was performed to determine MI recovery on day 1, 7 and 28. The transplanted rCPCs cell retention was detected using GFP expressing rCPCs and CD68⁺ cells on heart tissue by immune-histochemistry. Apoptotic cell death on injured myocardium was measured using TUNNEL assay. Sera collected on day 2, 7, 14, 21 and 28 were utilized to measure the inflammatory (IL-2, IL-17, IFN-γ, TGF-β), anti-inflammatory (IL-10) cytokines and antibodies against cardiac self-antigens (SAgs) Troponin-T and Myosin and allo antigens RT1A, RT1B and RT1D was measured using ELISA.

*Results: MI rats transplanted with aCPCs+CSA demonstrated significant increase in MI recovery and cell retention compared to MI rats with aCPCs, CSA and IMDM controls (p<0.05). MI rats transplanted with aCPCs showed increased infiltration of CD68⁺ cells and apoptotic cells in the infarcted myocardium compared to aCPCs+CSA group (p<0.05). Sera collected on day 2 and 7 of aCPCs group showed increased inflammatory cytokines, antibodies to cardiac SAgs and reduced anti-inflammatory cytokines. In contrast MI rats transplanted with aCPCs+CSA showed reduced inflammatory cytokines, abs to SAgs, allo antigens and increased anti-inflammatory cytokine IL-10 (p<0.05).

*Conclusions: In conclusion, MI rats transplanted with allogeneic aCPCs+CSA showed increased cell retention, reduced inflammatory cells and cytokines compared to aCPCs, CSA and IMDM control. Therefore, CSA reduces auto and allo immune response and increases the retention of transplanted aCPCs that resulted in increased myocardial recovery.

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