Abstract 20729: Allogenic Cardiac Progenitor Cells Are Immunosuppressive With Immune Regulatory Potentials

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Abstract

Introduction: Cardiac progenitor cells (CPCs) are an attractive cell type for cardiac regeneration. Although autologous CPC transplantation has demonstrated efficacy in a Phase I clinical trial in myocardial infarction (MI) patients but this involves time consuming expansion of patient-derived CPCs, which delays therapy. In this case therapeutic effectiveness of autologous CPCs is influenced by age and disease severity of patient itself. So the use of allogeneic CPCs is safe, effective and would obviate such limitations.

Hypothesis: In this study we aim to evaluate the immunogenicity and cardiac recovery potential of allogeneic CPCs in a rodent myocardial infarction (MI) model.

Methods and Results: Human CPCs (hCPCs) were isolated from adult patients undergoing coronary artery bypass grafting, and rat CPCs (rCPCs) were isolated from male Wistar-Kyoto (WKY) rat hearts. In vitro, hCPCs and rCPCs expressed major histocompatibility complex class I, but not class II antigens or co-stimulatory molecules (CD80, CD86). In mixed lymphocyte reaction assays, hCPCs inhibited T-cell proliferation and promoted T-regulatory cells, similar to human mesenchymal stem cells and human cardiosphere-derived cells (CDCs). But hCPCs also favored switching macrophages from a pro-inflammatory phenotype into a regulatory anti-inflammatory phenotype (M2). The in vivo functional potential of rCPCs was evaluated in the rodent MI model. In contrast to injected xenogeneic cells, injected allogeneic or syngeneic rCPCs significantly improved cardiac function and reduced myocardial fibrosis. Allogeneic CPCs induced immunosuppressive regulatory molecules like T regulatory cells (Treg), IL10, IL2 and M2 macrophages in the infarcted myocardium, which are anti-inflammatory and help to repair immune system.

Conclusion: Allogeneic CPCs are poorly immune stimulatory and elicit minimal inflammatory responses by increasing T-regulatory cells and M2 polarization both in vitro and in vivo, while maintaining their cardiac recovery potential and safety profile in a rodent MI model. Our observations strongly support the development of allogeneic CPCs therapy for broader patient applications.

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