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Development and Validation of a Fully GMP-Compliant Process for Manufacturing Stromal Vascular Fraction: A Cost-Effective Alternative to Automated Methods
The therapeutic use of adipose-derived stromal vascular fraction (SVF) is expanding in multiple pathologies. Various processes have been proposed for manufacturing SVF but they must be revisited based on advanced therapy medicinal product (ATMP) regulations. We report here the development and valida...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598595/ https://www.ncbi.nlm.nih.gov/pubmed/32987708 http://dx.doi.org/10.3390/cells9102158 |
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author | François, Pauline Giraudo, Laurent Veran, Julie Bertrand, Baptiste Dumoulin, Chloé Aboudou, Houssein Grimaud, Fanny Vogtensperger, Marie Velier, Mélanie Arnaud, Laurent Lyonnet, Luc Simoncini, Stéphanie Guillet, Benjamin Dignat-George, Françoise Magalon, Jérémy Sabatier, Florence |
author_facet | François, Pauline Giraudo, Laurent Veran, Julie Bertrand, Baptiste Dumoulin, Chloé Aboudou, Houssein Grimaud, Fanny Vogtensperger, Marie Velier, Mélanie Arnaud, Laurent Lyonnet, Luc Simoncini, Stéphanie Guillet, Benjamin Dignat-George, Françoise Magalon, Jérémy Sabatier, Florence |
author_sort | François, Pauline |
collection | PubMed |
description | The therapeutic use of adipose-derived stromal vascular fraction (SVF) is expanding in multiple pathologies. Various processes have been proposed for manufacturing SVF but they must be revisited based on advanced therapy medicinal product (ATMP) regulations. We report here the development and validation of a fully good manufacturing practices (GMP)-compliant protocol for the isolation of SVF. Adipose tissue was collected from healthy volunteers undergoing lipoaspiration. The optimal conditions of collagenase digestion and washing were determined based on measurements of SVF cell viability, yield recovery, and cell subset distribution. Comparability of the SVF obtained using the newly developed manufacturing process (n = 6) and the Celution-based automated method (n = 33), used as a reference, was established using inter-donor analyses. Characteristics of SVF (n = 5) generated using both manufacturing protocols were analyzed for an intra-donor comparison. In addition, these comparisons also included the determination of colony-forming unit fibroblast frequency, in vitro angiogenic activity, and in vivo regenerative effects in a mouse ischemic cutaneous wound model. We successfully developed a process for the generation of SVF presenting higher cell viability and yield recovery compared to the Celution device-based protocol. Characteristics of the SVF including phenotype, capacity for angiogenesis, and wound-healing promotion attested to the comparability of the two manufacturing processes. We validated an optimized non-automated process that should allow for a GMP-compliant, more affordable, and reduced-cost strategy to exploit the potential of SVF-based regenerative therapies. |
format | Online Article Text |
id | pubmed-7598595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75985952020-10-31 Development and Validation of a Fully GMP-Compliant Process for Manufacturing Stromal Vascular Fraction: A Cost-Effective Alternative to Automated Methods François, Pauline Giraudo, Laurent Veran, Julie Bertrand, Baptiste Dumoulin, Chloé Aboudou, Houssein Grimaud, Fanny Vogtensperger, Marie Velier, Mélanie Arnaud, Laurent Lyonnet, Luc Simoncini, Stéphanie Guillet, Benjamin Dignat-George, Françoise Magalon, Jérémy Sabatier, Florence Cells Article The therapeutic use of adipose-derived stromal vascular fraction (SVF) is expanding in multiple pathologies. Various processes have been proposed for manufacturing SVF but they must be revisited based on advanced therapy medicinal product (ATMP) regulations. We report here the development and validation of a fully good manufacturing practices (GMP)-compliant protocol for the isolation of SVF. Adipose tissue was collected from healthy volunteers undergoing lipoaspiration. The optimal conditions of collagenase digestion and washing were determined based on measurements of SVF cell viability, yield recovery, and cell subset distribution. Comparability of the SVF obtained using the newly developed manufacturing process (n = 6) and the Celution-based automated method (n = 33), used as a reference, was established using inter-donor analyses. Characteristics of SVF (n = 5) generated using both manufacturing protocols were analyzed for an intra-donor comparison. In addition, these comparisons also included the determination of colony-forming unit fibroblast frequency, in vitro angiogenic activity, and in vivo regenerative effects in a mouse ischemic cutaneous wound model. We successfully developed a process for the generation of SVF presenting higher cell viability and yield recovery compared to the Celution device-based protocol. Characteristics of the SVF including phenotype, capacity for angiogenesis, and wound-healing promotion attested to the comparability of the two manufacturing processes. We validated an optimized non-automated process that should allow for a GMP-compliant, more affordable, and reduced-cost strategy to exploit the potential of SVF-based regenerative therapies. MDPI 2020-09-24 /pmc/articles/PMC7598595/ /pubmed/32987708 http://dx.doi.org/10.3390/cells9102158 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article François, Pauline Giraudo, Laurent Veran, Julie Bertrand, Baptiste Dumoulin, Chloé Aboudou, Houssein Grimaud, Fanny Vogtensperger, Marie Velier, Mélanie Arnaud, Laurent Lyonnet, Luc Simoncini, Stéphanie Guillet, Benjamin Dignat-George, Françoise Magalon, Jérémy Sabatier, Florence Development and Validation of a Fully GMP-Compliant Process for Manufacturing Stromal Vascular Fraction: A Cost-Effective Alternative to Automated Methods |
title | Development and Validation of a Fully GMP-Compliant Process for Manufacturing Stromal Vascular Fraction: A Cost-Effective Alternative to Automated Methods |
title_full | Development and Validation of a Fully GMP-Compliant Process for Manufacturing Stromal Vascular Fraction: A Cost-Effective Alternative to Automated Methods |
title_fullStr | Development and Validation of a Fully GMP-Compliant Process for Manufacturing Stromal Vascular Fraction: A Cost-Effective Alternative to Automated Methods |
title_full_unstemmed | Development and Validation of a Fully GMP-Compliant Process for Manufacturing Stromal Vascular Fraction: A Cost-Effective Alternative to Automated Methods |
title_short | Development and Validation of a Fully GMP-Compliant Process for Manufacturing Stromal Vascular Fraction: A Cost-Effective Alternative to Automated Methods |
title_sort | development and validation of a fully gmp-compliant process for manufacturing stromal vascular fraction: a cost-effective alternative to automated methods |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598595/ https://www.ncbi.nlm.nih.gov/pubmed/32987708 http://dx.doi.org/10.3390/cells9102158 |
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