Abstract
Cardiac progenitor cells (CPCs) 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). Adult CPCs isolated from Wister Kyoto rat was transplanted into Brown Norway MI rats. MI rats transplanted with aCPCs+CsA demonstrated significant increase in MI recovery and cell retention compared to MI rats with aCPCs, CsA and Iscove Modified Dulbecco Media 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) analyzed by immunohistochemistry. Sera collected on day 2 and 7 of aCPCs group showed increased inflammatory cytokines (IL-2, IL-17, IFN-γ, TGF-β), antibodies to cardiac SAgs (Troponin-T and Myosin) allo antigens (RT1A, RT1B and RT1D) and reduced anti-inflammatory cytokines (IL-10). 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). In conclusion, MI rats transplanted with allogeneic aCPCs with immune suppressant 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 regeneration potential by increased transplanted aCPCs retention that resulted in enhanced myocardial recovery.
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