First-in-human PeriCord cardiac bioimplant: Scalability and GMP manufacturing of an allogeneic engineered tissue graft

Background: Small cardiac tissue engineering constructs show promise for limiting post-infarct sequelae in animal models. This study sought to scale-up a 2-cm2 preclinical construct into a human-size advanced therapy medicinal product (ATMP; PeriCord), and to test it in a first-in-human implantation...

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Detalles Bibliográficos
Autores: Prat Vidal, Cristina, Rodríguez Gomez, Luciano, Aylagas, Miriam, Nieto Nicolau, Núria, Gastelurrutia, Paloma, Agustí, Elba, Gálvez Montón, Carolina, Jorba, Ignasi, Teis, Albert, Monguió Tortajada, Marta, Roura, Santiago, Vives, Joaquim, Torrents Zapata, Silvia, Coca, María Isabel, Reales, Laura, Cámara Rosell, María Luisa, Cediel, Germán, Coll, Ruth, Farré Ventura, Ramon, Navajas Navarro, Daniel, Vilarrodona, Anna, García López, Joan, Muñoz Guijosa, Christian, Querol Giner, Sergi, Bayés Genís, Antoni
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/179267
Acceso en línea:https://hdl.handle.net/2445/179267
Access Level:acceso abierto
Palabra clave:Cirurgia cardiovascular
Infart de miocardi
Cardiovascular surgery
Myocardial infarction
Descripción
Sumario:Background: Small cardiac tissue engineering constructs show promise for limiting post-infarct sequelae in animal models. This study sought to scale-up a 2-cm2 preclinical construct into a human-size advanced therapy medicinal product (ATMP; PeriCord), and to test it in a first-in-human implantation. Methods: The PeriCord is a clinical-size (12-16 cm2) decellularised pericardial matrix colonised with human viable Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs). WJ-MSCs expanded following good manufacturing practices (GMP) met safety and quality standards regarding the number of cumulative population doublings, genomic stability, and sterility. Human decellularised pericardial scaffolds were tested for DNA content, matrix stiffness, pore size, and absence of microbiological growth. Findings: PeriCord implantation was surgically performed on a large non-revascularisable scar in the inferior wall of a 63-year-old male patient. Coronary artery bypass grafting was concomitantly performed in the non-infarcted area. At implantation, the 16-cm2 pericardial scaffold contained 12·5 × 106 viable WJ-MSCs (85·4% cell viability; <0·51 endotoxin units (EU)/mL). Intraoperative PeriCord delivery was expeditious, and secured with surgical glue. The post-operative course showed non-adverse reaction to the PeriCord, without requiring host immunosuppression. The three-month clinical follow-up was uneventful, and three-month cardiac magnetic resonance imaging showed ~9% reduction in scar mass in the treated area. Interpretation: This preliminary report describes the development of a scalable clinical-size allogeneic PeriCord cardiac bioimplant, and its first-in-human implantation.

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