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...

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Autores principales:	Annick Jeannerat, Cédric Peneveyre, Florence Armand, Diego Chiappe, Romain Hamelin, Corinne Scaletta, Nathalie Hirt-Burri, Anthony de Buys Roessingh, Wassim Raffoul, Lee Ann Applegate, Alexis Laurent
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	active pharmaceutical ingredients cell banking cell manufacture hypoxia human progenitor tenocytes optimization Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/dec4b8a9e444465f980e2e03665e212a
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spelling	oai:doaj.org-article:dec4b8a9e444465f980e2e03665e212a2021-11-25T17:08:21ZHypoxic Incubation Conditions for Optimized Manufacture of Tenocyte-Based Active Pharmaceutical Ingredients of Homologous Standardized Transplant Products in Tendon Regenerative Medicine10.3390/cells101128722073-4409https://doaj.org/article/dec4b8a9e444465f980e2e03665e212a2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2872https://doaj.org/toc/2073-4409Human 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<sub>2</sub> and 21% O<sub>2</sub>, standard conditions) or in hypoxic incubation (i.e., 5% CO<sub>2</sub> and 2% O<sub>2</sub>, 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.Annick JeanneratCédric PeneveyreFlorence ArmandDiego ChiappeRomain HamelinCorinne ScalettaNathalie Hirt-BurriAnthony de Buys RoessinghWassim RaffoulLee Ann ApplegateAlexis LaurentMDPI AGarticleactive pharmaceutical ingredientscell bankingcell manufacturehypoxiahuman progenitor tenocytesoptimizationBiology (General)QH301-705.5ENCells, Vol 10, Iss 2872, p 2872 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	active pharmaceutical ingredients cell banking cell manufacture hypoxia human progenitor tenocytes optimization Biology (General) QH301-705.5
spellingShingle	active pharmaceutical ingredients cell banking cell manufacture hypoxia human progenitor tenocytes optimization Biology (General) QH301-705.5 Annick Jeannerat Cédric Peneveyre Florence Armand Diego Chiappe Romain Hamelin Corinne Scaletta Nathalie Hirt-Burri Anthony de Buys Roessingh Wassim Raffoul Lee Ann Applegate Alexis Laurent Hypoxic Incubation Conditions for Optimized Manufacture of Tenocyte-Based Active Pharmaceutical Ingredients of Homologous Standardized Transplant Products in Tendon Regenerative Medicine
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<sub>2</sub> and 21% O<sub>2</sub>, standard conditions) or in hypoxic incubation (i.e., 5% CO<sub>2</sub> and 2% O<sub>2</sub>, 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	article
author	Annick Jeannerat Cédric Peneveyre Florence Armand Diego Chiappe Romain Hamelin Corinne Scaletta Nathalie Hirt-Burri Anthony de Buys Roessingh Wassim Raffoul Lee Ann Applegate Alexis Laurent
author_facet	Annick Jeannerat Cédric Peneveyre Florence Armand Diego Chiappe Romain Hamelin Corinne Scaletta Nathalie Hirt-Burri Anthony de Buys Roessingh Wassim Raffoul Lee Ann Applegate Alexis Laurent
author_sort	Annick Jeannerat
title	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_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_sort	hypoxic incubation conditions for optimized manufacture of tenocyte-based active pharmaceutical ingredients of homologous standardized transplant products in tendon regenerative medicine
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/dec4b8a9e444465f980e2e03665e212a
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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

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