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-cm(2) preclinical construct into a human-size advanced therapy medicinal product (ATMP; PeriCord), and to test it in a first-in-human implantati...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p13653 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=13653 |
| Access Level: | acceso abierto |
| Palabra clave: | Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs) Biofabrication Advanced therapy medicinal product (ATMP) Cardiac tissue engineering Scaffold Myocardial infarction |
| 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-cm(2) 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 cm(2)) 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-cm(2) pericardial scaffold contained 12.5 x 10(6) 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 similar to 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. (C) 2020 The Authors. Published by Elsevier B.V. |
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