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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Autores: Lopez-Diaz-de-Cerio, A. (Ascensión)|||/items/29ab6acb-fcbb-43ff-b4c1-e2dc95e22bcb, Pérez-Estenaga, I. (Iñigo)|||/items/0d3c0f0f-c86e-4bac-a8cb-20efdddb5d2d, Inoges-Sancho, S.I. (Susana Inmaculada)|||/items/3e5dc866-6d34-4005-b3bc-405b2bdf9992, Abizanda-Sarasa, G. (Gloria)|||/items/1e76a0e3-32d0-424e-b58a-d9ddf7a82ef7, Gavira-Gómez, J.J. (Juan José)|||/items/a253ead5-4ef7-4b80-9aab-43b47605270e, Larequi-Ardanaz, E. (Eduardo)|||/items/158060ea-c001-4d92-8334-e27ba510a24b, Andreu, E.J. (Enrique José)|||/items/bfb7adec-1ed3-4313-a2a7-8b026c48eba6, Rodriguez, S. (Saray)|||/items/c707d2b6-1137-4320-915b-4ffd88ad86f2, Gil-Royo, A.G. (Ana Gloria)|||/items/f54744d1-e54a-42e1-b5d0-cbabefd3fc53, Crisostomo, V. (Verónica)|||/items/0b0c70b3-3582-401a-9b27-07f908d589df, Sanchez-Margallo, F.M. (Francisco Miguel)|||/items/e1a34346-de03-4b94-a59a-669749ee20cc, Bermejo-Busto, J. (Javier)|||/items/e611de00-b172-42cd-a032-9759bea45434, Jauregui, B. (Blanca)|||/items/fca71b48-f655-4093-97d5-8aa818c2d14e, Quintana, L. (Lluis)|||/items/54ea730f-0168-4aa9-a6fa-3cf668be22ac, Fernandez-Aviles, F. (Francisco)|||/items/b2f2d78a-c943-4591-8b6f-73f5b11576f0, Pelacho-Samper, B. (Beatriz)|||/items/aca35c0e-183d-435d-9d44-1888e0854ff3, Prosper-Cardoso, F. (Felipe)|||/items/3d1b0b82-06c3-4e63-8280-e903dc4dc0c1
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/115116
Acceso en línea:https://hdl.handle.net/10171/115116
Access Level:acceso abierto
Palabra clave:Adipose-derived mesenchymal stromal cells
Allogeneic
Collagen scaffold
Myocardial infarction
Safety
Descripción
Sumario: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.

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