Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn Care
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/9/2334 |
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| author | Xi Chen Alexis Laurent Zhifeng Liao Sandra Jaccoud Philippe Abdel-Sayed Marjorie Flahaut Corinne Scaletta Wassim Raffoul Lee Ann Applegate Nathalie Hirt-Burri |
| author_facet | Xi Chen Alexis Laurent Zhifeng Liao Sandra Jaccoud Philippe Abdel-Sayed Marjorie Flahaut Corinne Scaletta Wassim Raffoul Lee Ann Applegate Nathalie Hirt-Burri |
| author_sort | Xi Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T22:15:22Z |
| format | Article |
| id | doaj.art-65e16a3ba0cc47408d51811888797ffd |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T22:15:22Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-65e16a3ba0cc47408d51811888797ffd2023-11-19T12:28:19ZengMDPI AGPharmaceutics1999-49232023-09-01159233410.3390/pharmaceutics15092334Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn CareXi Chen0Alexis Laurent1Zhifeng Liao2Sandra Jaccoud3Philippe Abdel-Sayed4Marjorie Flahaut5Corinne Scaletta6Wassim Raffoul7Lee Ann Applegate8Nathalie Hirt-Burri9Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, SwitzerlandPlastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, SwitzerlandPlastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, SwitzerlandPlastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, SwitzerlandPlastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, SwitzerlandPlastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, SwitzerlandPlastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, SwitzerlandPlastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, SwitzerlandPlastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, SwitzerlandPlastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, SwitzerlandAutologous 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.https://www.mdpi.com/1999-4923/15/9/2334autologous keratinocytesburn centercutaneous cell therapydermal templatedermo-epidermal graftsearly coverage solutions |
| spellingShingle | Xi Chen Alexis Laurent Zhifeng Liao Sandra Jaccoud Philippe Abdel-Sayed Marjorie Flahaut Corinne Scaletta Wassim Raffoul Lee Ann Applegate Nathalie Hirt-Burri Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn Care Pharmaceutics autologous keratinocytes burn center cutaneous cell therapy dermal template dermo-epidermal grafts early coverage solutions |
| title | Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn Care |
| title_full | Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn Care |
| title_fullStr | Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn Care |
| title_full_unstemmed | Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn Care |
| title_short | Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn Care |
| title_sort | cutaneous cell therapy manufacturing timeframe rationalization allogeneic off the freezer fibroblasts for dermo epidermal combined preparations de fe002 sk2 in burn care |
| topic | autologous keratinocytes burn center cutaneous cell therapy dermal template dermo-epidermal grafts early coverage solutions |
| url | https://www.mdpi.com/1999-4923/15/9/2334 |
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