Abstract
The use of allogeneic adipose-derived mesenchymal stromal cells (alloADSCs) represents an attractive approach for treating myocardial infarction (MI). Furthermore, adding a natural support improves alloADSCs engraftment and survival in heart tissues, leading to a greater therapeutic effect. We aimed to examine the safety and immunological reaction induced by epicardial implantation of a clinical-grade collagen scaffold (CS) seeded with alloADSCs for its future application in humans. Thus, cellularized scaffolds were myocardially or subcutaneously implanted in immunosuppressed rodent models. The toxicological parameters were not significantly altered, and tumor formation was not found over the short or long term. Furthermore, biodistribution analyses in the infarcted immunocompetent rats displayed cell engraftment in the myocardium but no migration to other organs. The immunogenicity of alloADSC-CS was also evaluated in a preclinical porcine model of chronic MI; no significant humoral or cellular alloreactive responses were found. Moreover, CS cellularized with human ADSCs cocultured with human allogeneic immune cells produced no alloreactive response. Interestingly, alloADSC-CS significantly inhibited lymphocyte responses, confirming its immunomodulatory action. Thus, alloADSC-CS is likely safe and does not elicit any alloreactive immunological response in the host. Moreover, it exerts an immunomodulatory action, which supports its translation to a clinical setting.
Highlights
Cardiovascular diseases (CVDs) are the leading cause of death worldwide
We demonstrated that the transplantation of allogeneic ADSC-collagen scaffold (CS) in a porcine model of chronic myocardial infarction (MI) is safe and does not induce an alloreactive response
The primary goal of this study was to examine the safety and immunological reaction induced by transplantation of a GMP-grade alloADSC-CS into the heart for its clinical use in patients with MI
Summary
According to the most recent report from the European Society of Cardiology, CVDs remain the most common cause of death in Europe, accounting for 4 million deaths per year. The therapeutic benefit of mesenchymal stromal cells (MSCs) has been extensively demonstrated in different experimental models of myocardial infarction (MI) [2]. Several clinical trials, including the recent MSC-HF, MESAMI, and ATHENA trials, have been performed in patients with chronic cardiomyopathies, confirming the safety and feasibility of autologous MSC transplantation [3,4,5]. The benefits of such treatments have been modest at best, as poor engraftment and survival of the injected cells hinder their therapeutic potential [6]. Several approaches have been explored to improve cell retention, including the use of natural or synthetic matrices to facilitate cell support [7]
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