Immunosuppression Increases Regenerative Potential of Adult Rat Cardiac Progenitor Cells in Allogeneic Rat Myocardial Infarction Model
Department of Surgery, University of Maryland, Baltimore 21201, MD
Meeting: 2019 American Transplant Congress
Abstract number: 597
Keywords: Heart failure, Inflammation, Rat, Stem cells
Session Information
Session Name: Concurrent Session: Stem Cell, Cellular Therapies and Regenerative Medicine
Session Type: Concurrent Session
Date: Tuesday, June 4, 2019
Session Time: 4:30pm-6:00pm
Presentation Time: 5:30pm-5:42pm
Location: Room 310
*Purpose: Cardiac progenitor cells (CPCs, c-kit+) are well-characterized stem cell type shown to potentiate cardiac regeneration in myocardial infarct (MI) model. However, 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 (1X106) to Brown Norway MI rats as aCPC group. Immune suppressant CSA were administered orally to MI rats with rCPCs transplantation grouped as aCPCs+CSA. 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 on heart tissue by immune-histochemistry (IHC). The rate of apoptotic cell death on injured myocardium was measured using TUNNEL assay. The inflammatory CD-68+ cells were measured by IHC. 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.
*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 CD-68+ 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 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 inflammation and increases the retention of transplanted aCPCs that resulted in increased myocardial recovery.
To cite this abstract in AMA style:
Gunasekaran M, Mishra R, Sharma S, Saha P, Arfat MY, Ambastha C, Morales D, Xuebin F, Bittle GJ, Li D, Kaushal S. Immunosuppression Increases Regenerative Potential of Adult Rat Cardiac Progenitor Cells in Allogeneic Rat Myocardial Infarction Model [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/immunosuppression-increases-regenerative-potential-of-adult-rat-cardiac-progenitor-cells-in-allogeneic-rat-myocardial-infarction-model/. Accessed May 12, 2025.« Back to 2019 American Transplant Congress