Preclinical Evaluation of the Safety and Immunological Action of Allogeneic ADSC-Collagen Scaffolds in the Treatment of Chronic Ischemic Cardiomyopathy

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...

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Published in:Pharmaceutics 2021-08, Vol.13 (8), p.1269
Main Authors: López-Díaz de Cerio, Ascensión, Perez-Estenaga, Iñigo, Inoges, Susana, Abizanda, Gloria, Gavira, Juan José, Larequi, Eduardo, Andreu, Enrique, Rodriguez, Saray, Gil, Ana Gloria, Crisostomo, Verónica, Sanchez-Margallo, Francisco Miguel, Bermejo, Javier, Jauregui, Blanca, Quintana, Lluis, Fernández-Avilés, Francisco, Pelacho, Beatriz, Prósper, Felipe
Format: Article
Language:English
Subjects:
adipose-derived mesenchymal stromal cells
allogeneic
Antibodies
Biocompatibility
Cardiomyopathy
Clinical trials
Collagen
collagen scaffold
Cytokines
Experiments
Females
Heart
Hogs
Immunology
Laboratory animals
Lymphocytes
Males
Medical technology
Mortality
myocardial infarction
safety
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Summary: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.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics13081269