Optimized Manufacture of Lyophilized Dermal Fibroblasts for Next-Generation Off-the-Shelf Progenitor Biological Bandages in Topical Post-Burn Regenerative Medicine

Laurent, Alexis; Scaletta, Corinne; Abdel-Sayed, Philippe; Michetti, Murielle; Flahaut, Marjorie; Simon, Jeanne-Pascale; Roessingh, Anthony de Buys; Raffoul, Wassim; Hirt-Burri, Nathalie; Applegate, Lee Ann

doi:10.3390/biomedicines9081072

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Optimized Manufacture of Lyophilized Dermal Fibroblasts for Next-Generation Off-the-Shelf Progenitor Biological Bandages in Topical Post-Burn Regenerative Medicine

^1,2,3,†,

^1,†,

¹,

¹,

⁴,

Anthony de Buys Roessingh

^5,6

Wassim Raffoul

^5,7

Nathalie Hirt-Burri

^1,‡ and

Lee Ann Applegate

^{1,5,8,9,*,‡}

Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Épalinges, Switzerland

Manufacturing Department, TEC-PHARMA SA, CH-1038 Bercher, Switzerland

Manufacturing Department, LAM Biotechnologies SA, CH-1066 Épalinges, Switzerland

⁴

Unit of Legal Affairs, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland

⁵

Romand Burn Center, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland

⁶

Children and Adolescent Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland

⁷

Plastic, Reconstructive, and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland

⁸

Center for Applied Biotechnology and Molecular Medicine, University of Zurich, CH-8057 Zurich, Switzerland

⁹

Oxford OSCAR Suzhou Center, Oxford University, Suzhou 215123, China

Author to whom correspondence should be addressed.

^†

Equal first co-authors.

^‡

Equal last co-authors.

Academic Editor: Bart De Geest

Biomedicines 2021, 9(8), 1072; https://doi.org/10.3390/biomedicines9081072

Received: 26 July 2021 / Revised: 18 August 2021 / Accepted: 20 August 2021 / Published: 23 August 2021

(This article belongs to the Special Issue New Insights in Gene and Cell Therapy)

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Abstract

Cultured fibroblast progenitor cells (FPC) have been studied in Swiss translational regenerative medicine for over two decades, wherein clinical experience was gathered for safely managing burns and refractory cutaneous ulcers. Inherent FPC advantages include high robustness, optimal adaptability to industrial manufacture, and potential for effective repair stimulation of wounded tissues. Major technical bottlenecks in cell therapy development comprise sustainability, stability, and logistics of biological material sources. Herein, we report stringently optimized and up-scaled processing (i.e., cell biobanking and stabilization by lyophilization) of dermal FPCs, with the objective of addressing potential cell source sustainability and stability issues with regard to active substance manufacturing in cutaneous regenerative medicine. Firstly, multi-tiered FPC banking was optimized in terms of overall quality and efficiency by benchmarking key reagents (e.g., medium supplement source, dissociation reagent), consumables (e.g., culture vessels), and technical specifications. Therein, fetal bovine serum batch identity and culture vessel surface were confirmed, among other parameters, to largely impact harvest cell yields. Secondly, FPC stabilization by lyophilization was undertaken and shown to maintain critical functions for devitalized cells in vitro, potentially enabling high logistical gains. Overall, this study provides the technical basis for the elaboration of next-generation off-the-shelf topical regenerative medicine therapeutic products for wound healing and post-burn care. View Full-Text

Keywords: cell biobanking; biotechnology; cell therapies; lyophilization; manufacturing optimization; organ donation; regenerative medicine; skin fibroblast progenitor cells; standardized transplants; wound healing

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MDPI and ACS Style

Laurent, A.; Scaletta, C.; Abdel-Sayed, P.; Michetti, M.; Flahaut, M.; Simon, J.-P.; Roessingh, A.d.B.; Raffoul, W.; Hirt-Burri, N.; Applegate, L.A. Optimized Manufacture of Lyophilized Dermal Fibroblasts for Next-Generation Off-the-Shelf Progenitor Biological Bandages in Topical Post-Burn Regenerative Medicine. Biomedicines 2021, 9, 1072. https://doi.org/10.3390/biomedicines9081072

AMA Style

Laurent A, Scaletta C, Abdel-Sayed P, Michetti M, Flahaut M, Simon J-P, Roessingh AdB, Raffoul W, Hirt-Burri N, Applegate LA. Optimized Manufacture of Lyophilized Dermal Fibroblasts for Next-Generation Off-the-Shelf Progenitor Biological Bandages in Topical Post-Burn Regenerative Medicine. Biomedicines. 2021; 9(8):1072. https://doi.org/10.3390/biomedicines9081072

Chicago/Turabian Style

Laurent, Alexis, Corinne Scaletta, Philippe Abdel-Sayed, Murielle Michetti, Marjorie Flahaut, Jeanne-Pascale Simon, Anthony de Buys Roessingh, Wassim Raffoul, Nathalie Hirt-Burri, and Lee Ann Applegate. 2021. "Optimized Manufacture of Lyophilized Dermal Fibroblasts for Next-Generation Off-the-Shelf Progenitor Biological Bandages in Topical Post-Burn Regenerative Medicine" Biomedicines 9, no. 8: 1072. https://doi.org/10.3390/biomedicines9081072

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Optimized Manufacture of Lyophilized Dermal Fibroblasts for Next-Generation Off-the-Shelf Progenitor Biological Bandages in Topical Post-Burn Regenerative Medicine

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