First-in-human PeriCord cardiac bioimplant : scalability and GMP manufacturing of an allogeneic engineered tissue graft
Prat-Vidal, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Rodríguez-Gómez, Luciano (Cell Therapy Service, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà)
Aylagas, Miriam (Hospital Universitari Vall d'Hebron)
Nieto-Nicolau, Núria (Banc de Sang i Teixits (Barcelona, Catalunya))
Gastelurrutia, Paloma (Institut d'Investigació Biomèdica de Bellvitge)
Agustí, Elba (Banc de Sang i Teixits (Barcelona, Catalunya))
Gálvez-Montón, Carolina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Jorba, Ignasi (Institut de Bioenginyeria de Catalunya)
Teis, Albert (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Monguió-Tortajada, Marta (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Rudilla, F. (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Vives Armengol, Joaquim (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Torrents-Zapata, Silvia (Banc de Sang i Teixits (Barcelona, Catalunya))
Coca, María Isabel (Banc de Sang i Teixits (Barcelona, Catalunya))
Reales, Laura (Banc de Sang i Teixits (Barcelona, Catalunya))
Cámara, Maria-Luisa (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Cediel, Germán (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Farré, Ramon (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Coll-Bonet, Ruth (Research and Education. Banc de Sang i Teixits)
Navajas, Daniel (Institut de Bioenginyeria de Catalunya)
Vilarrodona, Anna (Banc de Sang i Teixits (Barcelona, Catalunya))
García López, Joan (Banc de Sang i Teixits (Barcelona, Catalunya))
Muñoz-Guijosa, Christian (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Querol, Sergi (Hospital Universitari Vall d'Hebron)
Bayés-Genís, Antoni (Universitat Autònoma de Barcelona. Departament de Medicina)
Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol
Vall d'Hebron Institut de Recerca (VHIR)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2020
Abstract:	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. 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. 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 × 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 ~9% reduction in scar mass in the treated area. This preliminary report describes the development of a scalable clinical-size allogeneic PeriCord cardiac bioimplant, and its first-in-human implantation. La Marató de TV3 Foundation, Government of Catalonia, Catalan Society of Cardiology, "La Caixa" Banking Foundation, Spanish Ministry of Science, Innovation and Universities, Institute of Health Carlos III, and the European Regional Development Fund.
Grants:	Agencia Estatal de Investigación SAF2017-84324-C2-1-R Agencia Estatal de Investigación SAF2017-85574-R Agencia Estatal de Investigación DPI2017-83721-P Instituto de Salud Carlos III PI18/00256 Instituto de Salud Carlos III PIC18/00014 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-483
Note:	Altres ajuts: La Marató de TV3 Foundation, Government of Catalonia, Catalan Society of Cardiology, "La Caixa" Banking Foundation, Spanish Ministry of Science, Innovation and Universities, Institute of Health Carlos III, and the European Regional Development Fund.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs) ; Biofabrication ; Advanced therapy medicinal product (ATMP) ; Cardiac tissue engineering ; Scaffold ; Myocardial infarction
Published in:	EBioMedicine, Vol. 54 (april 2020) , ISSN 2352-3964

DOI: 10.1016/j.ebiom.2020.102729
PMID: 32304998

11 p, 2.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles