First-in-human PeriCord cardiac bioimplant: Scalability and GMP manufacturing of an allogeneic engineered tissue graft
Por:
Prat-Vidal, C, Rodriguez-Gomez, L, Aylagas, M, Nieto-Nicolau, N, Gastelurrutia, P, Agusti, E, Galvez-Monton, C, Jorba, I, Teis, A, Monguio-Tortajada, M, Roura, S, Vives, J, Torrents-Zapata, S, Coca, MI, Reales, L, Camara-Rosell, ML, Cediel, G, Coll, R, Farre, R, Navajas, D, Vilarrodona, A, Garcia-Lopez, J, Munoz-Guijosa, C, Querol, S, Bayes-Genis, A
Publicada:
1 abr 2020
Resumen:
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.
Filiaciones:
Prat-Vidal, C:
Germans Trias i Pujol Hlth Sci Res Inst, ICREC Res Program, Can Ruti Campus, Badalona, Spain
Germans Trias i Pujol Univ Hosp, Heart Inst iCor, Carretera Canyet S-N, Badalona 08916, Barcelona, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Inst Invest Biomed Bellvitge IDIBELL, Lhospitalet De Llobregat, Spain
Rodriguez-Gomez, L:
Banc Sang & Teixits, Cell Therapy Serv, Edifici Dr Frederic Duran i Jorda, Barcelona 08005, Spain
Aylagas, M:
Banc Sang & Teixits, Cell Therapy Serv, Edifici Dr Frederic Duran i Jorda, Barcelona 08005, Spain
Autonomous Univ Barcelona, Vall dHebron Res Inst, Transfus Med Grp, Barcelona, Spain
Nieto-Nicolau, N:
Banc Sang & Teixits BST, Barcelona Tissue Bank BTB, Barcelona, Spain
Gastelurrutia, P:
Germans Trias i Pujol Hlth Sci Res Inst, ICREC Res Program, Can Ruti Campus, Badalona, Spain
Germans Trias i Pujol Univ Hosp, Heart Inst iCor, Carretera Canyet S-N, Badalona 08916, Barcelona, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Inst Invest Biomed Bellvitge IDIBELL, Lhospitalet De Llobregat, Spain
Agusti, E:
Banc Sang & Teixits BST, Barcelona Tissue Bank BTB, Barcelona, Spain
Galvez-Monton, C:
Germans Trias i Pujol Hlth Sci Res Inst, ICREC Res Program, Can Ruti Campus, Badalona, Spain
Germans Trias i Pujol Univ Hosp, Heart Inst iCor, Carretera Canyet S-N, Badalona 08916, Barcelona, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Jorba, I:
Univ Barcelona, Inst Bioengn Catalonia IBEC, Barcelona Inst Sci & Technol, CIBERES, Barcelona, Spain
Teis, A:
Germans Trias i Pujol Univ Hosp, Heart Inst iCor, Carretera Canyet S-N, Badalona 08916, Barcelona, Spain
Monguio-Tortajada, M:
Germans Trias i Pujol Hlth Sci Res Inst, ICREC Res Program, Can Ruti Campus, Badalona, Spain
Germans Trias i Pujol Hlth Sci Res Inst, REMAR IVECAT Grp, Can Ruti Campus, Badalona, Spain
Roura, S:
Germans Trias i Pujol Hlth Sci Res Inst, ICREC Res Program, Can Ruti Campus, Badalona, Spain
Germans Trias i Pujol Univ Hosp, Heart Inst iCor, Carretera Canyet S-N, Badalona 08916, Barcelona, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Vives, J:
Banc Sang & Teixits, Cell Therapy Serv, Edifici Dr Frederic Duran i Jorda, Barcelona 08005, Spain
Autonomous Univ Barcelona, Vall dHebron Res Inst VHIR, Musculoskeletal Tissue Engn Grp, Passeig Vall dHebron 129-139, Barcelona 08035, Spain
Univ Autonoma Barcelona, Dept Med, Passeig Vall dHebron 129-139, Barcelona 08035, Spain
Torrents-Zapata, S:
Banc Sang & Teixits, Cell Therapy Serv, Edifici Dr Frederic Duran i Jorda, Barcelona 08005, Spain
Coca, MI:
Banc Sang & Teixits, Cell Therapy Serv, Edifici Dr Frederic Duran i Jorda, Barcelona 08005, Spain
Reales, L:
Banc Sang & Teixits, Cell Therapy Serv, Edifici Dr Frederic Duran i Jorda, Barcelona 08005, Spain
Camara-Rosell, ML:
Germans Trias i Pujol Univ Hosp, Heart Inst iCor, Carretera Canyet S-N, Badalona 08916, Barcelona, Spain
Cediel, G:
Germans Trias i Pujol Univ Hosp, Heart Inst iCor, Carretera Canyet S-N, Badalona 08916, Barcelona, Spain
Coll, R:
Passeig Taulat, Res & Educ Banc Sang & Teixits, Edifici Dr Frederic Duran i Jorda, Barcelona 08005, Spain
Farre, R:
Univ Barcelona IDIBAPS CIBERES, Sch Med & Hlth Sci, Unit Biophys & Bioengn, Barcelona, Spain
Navajas, D:
Univ Barcelona, Inst Bioengn Catalonia IBEC, Barcelona Inst Sci & Technol, CIBERES, Barcelona, Spain
Vilarrodona, A:
Banc Sang & Teixits BST, Barcelona Tissue Bank BTB, Barcelona, Spain
Garcia-Lopez, J:
Passeig Taulat, Res & Educ Banc Sang & Teixits, Edifici Dr Frederic Duran i Jorda, Barcelona 08005, Spain
Munoz-Guijosa, C:
Germans Trias i Pujol Univ Hosp, Heart Inst iCor, Carretera Canyet S-N, Badalona 08916, Barcelona, Spain
Querol, S:
Banc Sang & Teixits, Cell Therapy Serv, Edifici Dr Frederic Duran i Jorda, Barcelona 08005, Spain
Autonomous Univ Barcelona, Vall dHebron Res Inst, Transfus Med Grp, Barcelona, Spain
Bayes-Genis, A:
Germans Trias i Pujol Hlth Sci Res Inst, ICREC Res Program, Can Ruti Campus, Badalona, Spain
Germans Trias i Pujol Univ Hosp, Heart Inst iCor, Carretera Canyet S-N, Badalona 08916, Barcelona, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Passeig Vall dHebron 129-139, Barcelona 08035, Spain
Green Published, gold
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