Suchergebnisse

Medicament de teràpia avançada; Medicament en investigació; Translacional (regulació) ; Medicamento de terapia avanzada; Medicamento en investigación; Traslacional (regulación) ; Advanced therapy medicinal product; Investigational medicinal product; Translational (regulation) ; A systematic and ordered product development program, in compliance with current quality and regulatory standards, increases the likelihood of yielding a successful advanced therapy medicinal product (ATMP) for clinical use as safe and effective therapy. As this is a novel field, little accurate information is available regarding the steps to be followed, and the information to be produced to support the development and use of an ATMP. Notably, successful clinical translation can be somewhat cumbersome for academic researchers. In this article, we have provided a summary of the available information, supported by our experience in Spain throughout the development of an ATMP for myocardial infarction, from the pre-clinical stage to phase I clinical trial approval. ; This work was supported by the Spanish Cell Therapy Network (TerCel) [RD16/0011/0006 and RD16/0011/0028]; and CIBER Cardiovascular [CB16/11/00403] projects, as a part of the National R&D&I Plan, and was co-funded by the ISCIII-Sub-Directorate General for Research Assessment and Promotion and the European Regional Development Fund (ERDF); the Government of Catalonia: Agency for Management of University and Research Grants (AGAUR) [2017-SGR-483 and 2017-SGR-719], PERIS Program (Health Department) [SLT002/16/00234 and SLT002/16/00209] and CERCA Program; La Caixa Banking Foundation; grants from the Spanish Ministry of Science, Innovation and Universities (MICINN) [SAF2017-84324-C2-1-R]; Institute of Health Carlos III (ISCIII) [PI18/00256, PIC18/00014, ICI19/00039, and PI19/01788], and cofunded by European Union (ERDF/ESF) - A way to build Europe. This work has also been funded by the Sociedad Española de Cardiología and by the Call for Expression of Interest (EoI) for Collaborative Projects on Regenerative Medicine 2019 of Center for Regenerative Medicine of Barcelona (CMR[B]). The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

[EN] Contractile restoration of myocardial scars remains a challenge with important clinical implications. Here, a combination of porous elastomeric membrane, peptide hydrogel, and subcutaneous adipose tissue-derived progenitor cells (subATDPCs) was designed and evaluated as a bioimplant for cardiac regeneration in a mouse model of myocardial infarction. SubATDPCs were doubly transduced with lentiviral vectors to express bioluminescent-fluorescent reporters driven by constitutively active, cardiac tissue-specific promoters. Cells were seeded into an engineered bioimplant consisting of a scaffold (polycaprolactone methacryloyloxyethyl ester) filled with a peptide hydrogel (PuraMatrix(TM)), and transplanted to cover injured myocardium. Bioluminescence and fluorescence quantifications showed de novo and progressive increases in promoter expression in bioactive implant-treated animals. The bioactive implant was well adapted to the heart, and fully functional vessels traversed the myocardium-bioactive implant interface. Treatment translated into a detectable positive effect on cardiac function, as revealed by echocardiography. Thus, this novel implant is a promising construct for supporting myocardial regeneration. ; The research leading to these results received funding from the European Union Seventh Framework Programme (Project RECATABI, 7FP/2007-2013) under grant agreement number 229239. This work was also supported by Ministerio de Ciencia e Innovación (SAF2011- 30067-C02-01), Fundació La Marató de TV3 (080330), Red de Terapia Celular-TerCel (RD12/0019/0029), Red Cardio-vascular (RD12/0042/0047), Sociedad Española de Cardiología, and Fundació Privada Daniel Bravo Andreu ; Soler-Botija, C.; Bago, JR.; Llucia-Valldeperas, A.; Vallés Lluch, A.; Castells-Sala, C.; Martinez-Ramos, C.; Fernandez-Muinos, T. (2014). Engineered 3D bioimplants using elastomeric scaffold, self-assembling peptide hydrogel, and adipose tissue-derived progenitor cells for cardiac regeneration. American Journal of Translational Research. ...

[EN] Ischemia produced as a result of myocardial infarction might cause moderate or severe tissue death. Studies under development propose grafting stem cells into the affected area and we hypothesize that this mechanism could be enhanced by the application of a "bioactive implant." The implant herein proposed consists of a thin porous elastomeric membrane, filled with self-assembling nanofibers and human subcutaneous adipose tissue derived progenitor cells. We describe the development and characterization of two elastomeric membranes: poly(ethyl acrylate) (PEA) and poly(caprolactone 2-(methacryloyloxy) ethyl ester) (PCLMA). Both are a good material support to deliver cells within a soft self-assembling peptide and are elastic enough to withstand the stresses arising from the heartbeat. Both developed composites (PEA and PCLMA, combined with self-assembling peptide) equally facilitate the propagation of electrical pulses and maintain their genetic profile of the seeded cells. Preliminary studies with small animal models suggest that, at short times, the bioimplant shows good adhesion with the myocardium. After three days cells loaded in the patch remain alive at the implanted site. We propose that the bioactive patch (elastomeric membranes with self-assembling peptide and cells) could increase the efficacy of future cardiac cell therapy by improving cell immobilization and survival at the affected site. ; The authors wish to thank the Department of Cardiac Surgery (Hospital Germans Trias i Pujol, Badalona) for their collaboration in obtaining human samples, Dr. Bago for his kind contribution in the cell transduction process and BLI analysis, and Joan Gilabert from Biomaterials Laboratory (GEMAT, IQS-School of Engineering) who kindly helped them with wettability measurements. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant agreement no. 229239. This work was also supported by Grants from Ministerio de Educacion y Ciencia ...

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 × 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. INTERPRETATION: This preliminary report describes the development of a scalable clinical-size allogeneic PeriCord cardiac bioimplant, and its first-in-human implantation. FUNDING: 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.