Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn Care.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_9797A6B9E5DD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn Care.
Périodique
Pharmaceutics
Auteur⸱e⸱s
Chen X., Laurent A., Liao Z., Jaccoud S., Abdel-Sayed P., Flahaut M., Scaletta C., Raffoul W., Applegate L.A., Hirt-Burri N.
ISSN
1999-4923 (Print)
ISSN-L
1999-4923
Statut éditorial
Publié
Date de publication
16/09/2023
Peer-reviewed
Oui
Volume
15
Numéro
9
Pages
2334
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Autologous cell therapy manufacturing timeframes constitute bottlenecks in clinical management pathways of severe burn patients. While effective temporary wound coverings exist for high-TBSA burns, any means to shorten the time-to-treatment with cytotherapeutic skin grafts could provide substantial therapeutic benefits. This study aimed to establish proofs-of-concept for a novel combinational cytotherapeutic construct (autologous/allogeneic DE-FE002-SK2 full dermo-epidermal graft) designed for significant cutaneous cell therapy manufacturing timeframe rationalization. Process development was based on several decades (four for autologous protocols, three for allogeneic protocols) of in-house clinical experience in cutaneous cytotherapies. Clinical grade dermal progenitor fibroblasts (standardized FE002-SK2 cell source) were used as off-the-freezer substrates in novel autologous/allogeneic dermo-epidermal bilayer sheets. Under vitamin C stimulation, FE002-SK2 primary progenitor fibroblasts rapidly produced robust allogeneic dermal templates, allowing patient keratinocyte attachment in co-culture. Notably, FE002-SK2 primary progenitor fibroblasts significantly outperformed patient fibroblasts for collagen deposition. An ex vivo de-epidermalized dermis model was used to demonstrate the efficient DE-FE002-SK2 construct bio-adhesion properties. Importantly, the presented DE-FE002-SK2 manufacturing process decreased clinical lot production timeframes from 6-8 weeks (standard autologous combined cytotherapies) to 2-3 weeks. Overall, these findings bear the potential to significantly optimize burn patient clinical pathways (for rapid wound closure and enhanced tissue healing quality) by combining extensively clinically proven cutaneous cell-based technologies.
Mots-clé
FE002 dermal progenitor fibroblasts, autologous keratinocytes, burn center, cutaneous cell therapy, dermal template, dermo-epidermal grafts, early coverage solutions, manufacturing optimization, severe burns, standardized skin grafts
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/10/2023 13:32
Dernière modification de la notice
08/08/2024 6:37
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