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© 2024 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Background/Objectives: Biological products are emerging as therapeutic management options for intervertebral disc (IVD) degenerative affections and lower back pain. Autologous and allogeneic cell therapy protocols have been clinically implemented for IVD repair. Therein, several manufacturing process design considerations were shown to significantly influence clinical outcomes. The primary objective of this study was to preclinically qualify (chondrogenic potential, safety, resistance to hypoxic and inflammatory stimuli) cryopreserved primary progenitor cells (clinical grade FE002-Disc cells) as a potential cell source in IVD repair/regeneration. The secondary objective of this study was to assess the cell source’s delivery potential as cell spheroids (optimization of culture conditions, potential storage solutions). Methods/Results: Safety (soft agar transformation, β-galactosidase, telomerase activity) and functionality-related assays (hypoxic and inflammatory challenge) confirmed that the investigated cellular active substance was highly sustainable in defined cell banking workflows, despite possessing a finite in vitro lifespan. Functionality-related assays confirmed that the retained manufacturing process yielded strong collagen II and glycosaminoglycan (GAG) synthesis in the spheroids in 3-week chondrogenic induction. Then, the impacts of various process parameters (induction medium composition, hypoxic incubation, terminal spheroid lyophilization) were studied to gain insights on their criticality. Finally, an optimal set of technical specifications (use of 10 nM dexamethasone for chondrogenic induction, 2% O2 incubation of spheroids) was set forth, based on specific fine tuning of finished product critical functional attributes. Conclusions: Generally, this study qualified the considered FE002-Disc progenitor cell source for further preclinical investigation based on safety, quality, and functionality datasets. The novelty and significance of this study resided in the establishment of defined processes for preparing fresh, off-the-freezer, or off-the-shelf IVD spheroids using a preclinically qualified allogeneic human cell source. Overall, this study underscored the importance of using robust product components and optimal manufacturing process variants for maximization of finished cell-based formulation quality attributes.

Details

Title
Banked Primary Progenitor Cells for Allogeneic Intervertebral Disc (IVD) Therapy: Preclinical Qualification and Functional Optimization within a Cell Spheroid Formulation Process
Author
Jeannerat, Annick 1 ; Peneveyre, Cédric 1 ; Jaccoud, Sandra 2 ; Philippe, Virginie 3   VIAFID ORCID Logo  ; Scaletta, Corinne 4 ; Hirt-Burri, Nathalie 4   VIAFID ORCID Logo  ; Abdel-Sayed, Philippe 5   VIAFID ORCID Logo  ; Martin, Robin 6 ; Applegate, Lee Ann 7   VIAFID ORCID Logo  ; Pioletti, Dominique P 8   VIAFID ORCID Logo  ; Laurent, Alexis 9   VIAFID ORCID Logo 

 Development Department, LAM Biotechnologies SA, CH-1066 Epalinges, Switzerland; [email protected] (A.J.); [email protected] (C.P.) 
 Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland; [email protected] (S.J.); [email protected] (V.P.); [email protected] (C.S.); [email protected] (N.H.-B.); [email protected] (P.A.-S.); [email protected] (L.A.A.); Laboratory of Biomechanical Orthopedics, Federal Polytechnic School of Lausanne, CH-1015 Lausanne, Switzerland 
 Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland; [email protected] (S.J.); [email protected] (V.P.); [email protected] (C.S.); [email protected] (N.H.-B.); [email protected] (P.A.-S.); [email protected] (L.A.A.); Orthopedics and Traumatology Unit, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland; [email protected] 
 Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland; [email protected] (S.J.); [email protected] (V.P.); [email protected] (C.S.); [email protected] (N.H.-B.); [email protected] (P.A.-S.); [email protected] (L.A.A.) 
 Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland; [email protected] (S.J.); [email protected] (V.P.); [email protected] (C.S.); [email protected] (N.H.-B.); [email protected] (P.A.-S.); [email protected] (L.A.A.); STI School of Engineering, Federal Polytechnic School of Lausanne, CH-1015 Lausanne, Switzerland 
 Orthopedics and Traumatology Unit, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland; [email protected] 
 Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland; [email protected] (S.J.); [email protected] (V.P.); [email protected] (C.S.); [email protected] (N.H.-B.); [email protected] (P.A.-S.); [email protected] (L.A.A.); Center for Applied Biotechnology and Molecular Medicine, University of Zurich, CH-8057 Zurich, Switzerland; Oxford OSCAR Suzhou Center, Oxford University, Suzhou 215123, China 
 Laboratory of Biomechanical Orthopedics, Federal Polytechnic School of Lausanne, CH-1015 Lausanne, Switzerland 
 Development Department, LAM Biotechnologies SA, CH-1066 Epalinges, Switzerland; [email protected] (A.J.); [email protected] (C.P.); Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland; [email protected] (S.J.); [email protected] (V.P.); [email protected] (C.S.); [email protected] (N.H.-B.); [email protected] (P.A.-S.); [email protected] (L.A.A.) 
First page
1274
Publication year
2024
Publication date
2024
Publisher
MDPI AG
e-ISSN
19994923
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3120740753
Copyright
© 2024 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.