Preclinical Evaluation of the Safety and Immunological Action of Allogeneic ADSC-Collagen Scaffolds in the Treatment of Chronic Ischemic Cardiomyopathy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Characterization of ADSCs and Production of Cellularized Collagen Scaffolds
2.2. Rat and Minipig MI Models
2.3. ADSC-CS Safety Assessment in Rodent Models
2.4. Implantation of alloADSC-CS in a Preclinical Porcine Model of MI
2.5. In Vitro Coculture of alloADSC-CS and PBMCs
3. Results
3.1. Safety Assessment of ADSC-CS
3.2. Inflammatory and Immunomodulatory Action of Allogeneic Pig ADSC-CS
3.3. In Vitro Assessment of Human ADSC-CS Immunomodulatory Action
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Time-Point | Findings | MI-ADSC-CS | MI-CS | Sham-ADSC-CS | Sham | ||||
---|---|---|---|---|---|---|---|---|---|
Day 2 | Sex (N° of animals) | Males (3) | Females (3) | Males (3) | Females (3) | Males (3) | Females (3) | Males (3) | Females (3) |
Remains of matrix | 3 | 3 | 3 | 3 | 3 | 2 | - | - | |
Inflammation, acute, pericardium | 3 (2.3) | 3 (1.3) | 3 (1.3) | 3 (1.3) | 3 (1.3) | 1 (2.0) | - | - | |
Myocardial necrosis | 3 (3.0) | 3 (3.0) | 3 (3.0) | 3 (2.7) | - | - | - | - | |
Macrophage aggregates | 3 (3.0) | 3 (1.7) | 3 (2.3) | 3 (2.0) | 3 (2.0) | 3 (1.3) | - | - | |
Pigmented macrophages | - | 1 (1.0) | 3 (1.0) | 3 (1.3) | - | - | - | - | |
Epicardial fibrosis | 3 (1.3) | 3 (1.7) | 3 (1.7) | 3 (1.0) | 2 (1.5) | 2 (2.0) | - | - | |
Multinucleated giant cells | - | - | - | - | - | - | - | - | |
Day 10 | Sex (N° of animals) | Males (3) | Females (3) | Males (3) | Females (3) | Males (3) | Females (3) | Males (3) | Females (3) |
Remains of matrix | 3 | 3 | 3 | 3 | 3 | 2 | - | - | |
Inflammation, acute, pericardium | - | - | - | - | - | - | - | - | |
Myocardial necrosis | 3 (3.0) | 3 (3.0) | 3 (3.0) | 3 (2.7) | - | - | - | - | |
Macrophage aggregates | 3 (3.0) | 3 (1.7) | 3 (2.3) | 3 (2.0) | 3 (2.0) | 3 (1.3) | - | - | |
Pigmented macrophages | - | 1 (1.0) | 3 (1.0) | 3 (1.3) | - | - | - | - | |
Epicardial fibrosis | 3 (1.3) | 3 (1.7) | 3 (1.7) | 3 (1.0) | 2 (1.5) | 2 (2.0) | - | - | |
Multinucleated giant cells | - | - | - | - | - | - | - | - | |
Day 90 | Sex (N° of animals) | Males (5) | Females (5) | Males (5) | Females (5) | Males (5) | Females (5) | Males (5) | Females (5) |
Remains of matrix | 0 | 0 | 1 | 0 | 0 | 1 | - | - | |
Inflammation, acute, pericardium | - | - | - | - | - | - | - | - | |
Myocardial necrosis | - | - | - | - | - | 1 (2.0) | - | - | |
Macrophage aggregates | - | - | - | - | - | - | - | - | |
Pigmented macrophages | 4 (1.5) | 4 (1.0) | 2 (1.0) | 1 (1.0) | - | 3 (1.0) | -- | - | |
Epicardial fibrosis | 5 (2.4) | 4 (1.8) | - | - | 2 (2.5) | 5 (2.2) | - | - | |
Multinucleated giant cells | 1 (1.0) | - | - | - | - | - | - | - | |
Myocardial mineralization | 5 (2.8) | 1 (3.0) | 1 (2.0) | - | - | - | - | - |
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López-Díaz de Cerio, A.; Perez-Estenaga, I.; Inoges, S.; Abizanda, G.; Gavira, J.J.; Larequi, E.; Andreu, E.; Rodriguez, S.; Gil, A.G.; Crisostomo, V.; et al. Preclinical Evaluation of the Safety and Immunological Action of Allogeneic ADSC-Collagen Scaffolds in the Treatment of Chronic Ischemic Cardiomyopathy. Pharmaceutics 2021, 13, 1269. https://doi.org/10.3390/pharmaceutics13081269
López-Díaz de Cerio A, Perez-Estenaga I, Inoges S, Abizanda G, Gavira JJ, Larequi E, Andreu E, Rodriguez S, Gil AG, Crisostomo V, et al. Preclinical Evaluation of the Safety and Immunological Action of Allogeneic ADSC-Collagen Scaffolds in the Treatment of Chronic Ischemic Cardiomyopathy. Pharmaceutics. 2021; 13(8):1269. https://doi.org/10.3390/pharmaceutics13081269
Chicago/Turabian StyleLópez-Díaz de Cerio, Ascensión, Iñigo Perez-Estenaga, Susana Inoges, Gloria Abizanda, Juan José Gavira, Eduardo Larequi, Enrique Andreu, Saray Rodriguez, Ana Gloria Gil, Verónica Crisostomo, and et al. 2021. "Preclinical Evaluation of the Safety and Immunological Action of Allogeneic ADSC-Collagen Scaffolds in the Treatment of Chronic Ischemic Cardiomyopathy" Pharmaceutics 13, no. 8: 1269. https://doi.org/10.3390/pharmaceutics13081269
APA StyleLópez-Díaz de Cerio, A., Perez-Estenaga, I., Inoges, S., Abizanda, G., Gavira, J. J., Larequi, E., Andreu, E., Rodriguez, S., Gil, A. G., Crisostomo, V., Sanchez-Margallo, F. M., Bermejo, J., Jauregui, B., Quintana, L., Fernández-Avilés, F., Pelacho, B., & Prósper, F. (2021). Preclinical Evaluation of the Safety and Immunological Action of Allogeneic ADSC-Collagen Scaffolds in the Treatment of Chronic Ischemic Cardiomyopathy. Pharmaceutics, 13(8), 1269. https://doi.org/10.3390/pharmaceutics13081269