Allogenic Cardiac Progenitor Cells Transplantation with Immune Suppressant Cyclosporine a Recovers Myocardial Infarction in Rodent Model
Pediatrics, Lurie Childrens Hospital, Chicago, IL
Meeting: 2022 American Transplant Congress
Abstract number: 1514
Keywords: Autoimmunity, Heart failure, Rat, Stem cells
Topic: Basic Science » Basic Science » 05 - Translational Cellular Therapies: Islet and Stem Cell Transplantation
Session Information
Session Name: Translational Cellular Therapies: Islet and Stem Cell Transplantation
Session Type: Poster Abstract
Date: Tuesday, June 7, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: 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).
*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 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).
*Conclusions: 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.
To cite this abstract in AMA style:
Gunasekaran M, Mishra R, Sharma S, Saha P, Chen L, Guru S, Stefanowicz A, Bilewska A, Zarinebaf S, Zhi-Dong G, Kaushal S. Allogenic Cardiac Progenitor Cells Transplantation with Immune Suppressant Cyclosporine a Recovers Myocardial Infarction in Rodent Model [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/allogenic-cardiac-progenitor-cells-transplantation-with-immune-suppressant-cyclosporine-a-recovers-myocardial-infarction-in-rodent-model/. Accessed May 18, 2025.« Back to 2022 American Transplant Congress