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Hypoxic Incubation Conditions for Optimized Manufacture of Tenocyte-Based Active Pharmaceutical Ingredients of Homologous Standardized Transplant Products in Tendon Regenerative Medicine
Human fetal progenitor tenocytes (hFPT) produced in defined cell bank systems have recently been characterized and qualified as potential therapeutic cell sources in tendon regenerative medicine. In view of further developing the manufacture processes of such cell-based active pharmaceutical ingredi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616528/ https://www.ncbi.nlm.nih.gov/pubmed/34831095 http://dx.doi.org/10.3390/cells10112872 |
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author | Jeannerat, Annick Peneveyre, Cédric Armand, Florence Chiappe, Diego Hamelin, Romain Scaletta, Corinne Hirt-Burri, Nathalie de Buys Roessingh, Anthony Raffoul, Wassim Applegate, Lee Ann Laurent, Alexis |
author_facet | Jeannerat, Annick Peneveyre, Cédric Armand, Florence Chiappe, Diego Hamelin, Romain Scaletta, Corinne Hirt-Burri, Nathalie de Buys Roessingh, Anthony Raffoul, Wassim Applegate, Lee Ann Laurent, Alexis |
author_sort | Jeannerat, Annick |
collection | PubMed |
description | Human fetal progenitor tenocytes (hFPT) produced in defined cell bank systems have recently been characterized and qualified as potential therapeutic cell sources in tendon regenerative medicine. In view of further developing the manufacture processes of such cell-based active pharmaceutical ingredients (API), the effects of hypoxic in vitro culture expansion on key cellular characteristics or process parameters were evaluated. To this end, multiple aspects were comparatively assessed in normoxic incubation (i.e., 5% CO(2) and 21% O(2), standard conditions) or in hypoxic incubation (i.e., 5% CO(2) and 2% O(2), optimized conditions). Experimentally investigated parameters and endpoints included cellular proliferation, cellular morphology and size distribution, cell surface marker panels, cell susceptibility toward adipogenic and osteogenic induction, while relative protein expression levels were analyzed by quantitative mass spectrometry. The results outlined conserved critical cellular characteristics (i.e., cell surface marker panels, cellular phenotype under chemical induction) and modified key cellular parameters (i.e., cell size distribution, endpoint cell yields, matrix protein contents) potentially procuring tangible benefits for next-generation cell manufacturing workflows. Specific proteomic analyses further shed some light on the cellular effects of hypoxia, potentially orienting further hFPT processing for cell-based, cell-free API manufacture. Overall, this study indicated that hypoxic incubation impacts specific hFPT key properties while preserving critical quality attributes (i.e., as compared to normoxic incubation), enabling efficient manufacture of tenocyte-based APIs for homologous standardized transplant products. |
format | Online Article Text |
id | pubmed-8616528 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86165282021-11-26 Hypoxic Incubation Conditions for Optimized Manufacture of Tenocyte-Based Active Pharmaceutical Ingredients of Homologous Standardized Transplant Products in Tendon Regenerative Medicine Jeannerat, Annick Peneveyre, Cédric Armand, Florence Chiappe, Diego Hamelin, Romain Scaletta, Corinne Hirt-Burri, Nathalie de Buys Roessingh, Anthony Raffoul, Wassim Applegate, Lee Ann Laurent, Alexis Cells Article Human fetal progenitor tenocytes (hFPT) produced in defined cell bank systems have recently been characterized and qualified as potential therapeutic cell sources in tendon regenerative medicine. In view of further developing the manufacture processes of such cell-based active pharmaceutical ingredients (API), the effects of hypoxic in vitro culture expansion on key cellular characteristics or process parameters were evaluated. To this end, multiple aspects were comparatively assessed in normoxic incubation (i.e., 5% CO(2) and 21% O(2), standard conditions) or in hypoxic incubation (i.e., 5% CO(2) and 2% O(2), optimized conditions). Experimentally investigated parameters and endpoints included cellular proliferation, cellular morphology and size distribution, cell surface marker panels, cell susceptibility toward adipogenic and osteogenic induction, while relative protein expression levels were analyzed by quantitative mass spectrometry. The results outlined conserved critical cellular characteristics (i.e., cell surface marker panels, cellular phenotype under chemical induction) and modified key cellular parameters (i.e., cell size distribution, endpoint cell yields, matrix protein contents) potentially procuring tangible benefits for next-generation cell manufacturing workflows. Specific proteomic analyses further shed some light on the cellular effects of hypoxia, potentially orienting further hFPT processing for cell-based, cell-free API manufacture. Overall, this study indicated that hypoxic incubation impacts specific hFPT key properties while preserving critical quality attributes (i.e., as compared to normoxic incubation), enabling efficient manufacture of tenocyte-based APIs for homologous standardized transplant products. MDPI 2021-10-25 /pmc/articles/PMC8616528/ /pubmed/34831095 http://dx.doi.org/10.3390/cells10112872 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jeannerat, Annick Peneveyre, Cédric Armand, Florence Chiappe, Diego Hamelin, Romain Scaletta, Corinne Hirt-Burri, Nathalie de Buys Roessingh, Anthony Raffoul, Wassim Applegate, Lee Ann Laurent, Alexis Hypoxic Incubation Conditions for Optimized Manufacture of Tenocyte-Based Active Pharmaceutical Ingredients of Homologous Standardized Transplant Products in Tendon Regenerative Medicine |
title | Hypoxic Incubation Conditions for Optimized Manufacture of Tenocyte-Based Active Pharmaceutical Ingredients of Homologous Standardized Transplant Products in Tendon Regenerative Medicine |
title_full | Hypoxic Incubation Conditions for Optimized Manufacture of Tenocyte-Based Active Pharmaceutical Ingredients of Homologous Standardized Transplant Products in Tendon Regenerative Medicine |
title_fullStr | Hypoxic Incubation Conditions for Optimized Manufacture of Tenocyte-Based Active Pharmaceutical Ingredients of Homologous Standardized Transplant Products in Tendon Regenerative Medicine |
title_full_unstemmed | Hypoxic Incubation Conditions for Optimized Manufacture of Tenocyte-Based Active Pharmaceutical Ingredients of Homologous Standardized Transplant Products in Tendon Regenerative Medicine |
title_short | Hypoxic Incubation Conditions for Optimized Manufacture of Tenocyte-Based Active Pharmaceutical Ingredients of Homologous Standardized Transplant Products in Tendon Regenerative Medicine |
title_sort | hypoxic incubation conditions for optimized manufacture of tenocyte-based active pharmaceutical ingredients of homologous standardized transplant products in tendon regenerative medicine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616528/ https://www.ncbi.nlm.nih.gov/pubmed/34831095 http://dx.doi.org/10.3390/cells10112872 |
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