Autologous and Allogeneic Cytotherapies for Large Knee (Osteo)Chondral Defects: Manufacturing Process Benchmarking and Parallel Functional Qualification

Author:

Philippe Virginie12,Jeannerat Annick3,Peneveyre Cédric3,Jaccoud Sandra24,Scaletta Corinne2,Hirt-Burri Nathalie2ORCID,Abdel-Sayed Philippe25ORCID,Raffoul Wassim2ORCID,Darwiche Salim67ORCID,Applegate Lee Ann278ORCID,Martin Robin1ORCID,Laurent Alexis23ORCID

Affiliation:

1. Orthopedics and Traumatology Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland

2. Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland

3. Preclinical Research Department, LAM Biotechnologies SA, CH-1066 Epalinges, Switzerland

4. Laboratory of Biomechanical Orthopedics, Federal Polytechnic School of Lausanne, CH-1015 Lausanne, Switzerland

5. STI School of Engineering, Federal Polytechnic School of Lausanne, CH-1015 Lausanne, Switzerland

6. Musculoskeletal Research Unit, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, Switzerland

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

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

Abstract

Cytotherapies are often necessary for the management of symptomatic large knee (osteo)-chondral defects. While autologous chondrocyte implantation (ACI) has been clinically used for 30 years, allogeneic cells (clinical-grade FE002 primary chondroprogenitors) have been investigated in translational settings (Swiss progenitor cell transplantation program). The aim of this study was to comparatively assess autologous and allogeneic approaches (quality, safety, functional attributes) to cell-based knee chondrotherapies developed for clinical use. Protocol benchmarking from a manufacturing process and control viewpoint enabled us to highlight the respective advantages and risks. Safety data (telomerase and soft agarose colony formation assays, high passage cell senescence) and risk analyses were reported for the allogeneic FE002 cellular active substance in preparation for an autologous to allogeneic clinical protocol transposition. Validation results on autologous bioengineered grafts (autologous chondrocyte-bearing Chondro-Gide scaffolds) confirmed significant chondrogenic induction (COL2 and ACAN upregulation, extracellular matrix synthesis) after 2 weeks of co-culture. Allogeneic grafts (bearing FE002 primary chondroprogenitors) displayed comparable endpoint quality and functionality attributes. Parameters of translational relevance (transport medium, finished product suturability) were validated for the allogeneic protocol. Notably, the process-based benchmarking of both approaches highlighted the key advantages of allogeneic FE002 cell-bearing grafts (reduced cellular variability, enhanced process standardization, rationalized logistical and clinical pathways). Overall, this study built on our robust knowledge and local experience with ACI (long-term safety and efficacy), setting an appropriate standard for further clinical investigations into allogeneic progenitor cell-based orthopedic protocols.

Funder

S.A.N.T.E

Sandoz Foundations

Lausanne Orthopedics Research Foundation

Service of Promotion of the Economy and Innovation of the Canton of Vaud

Publisher

MDPI AG

Subject

Pharmaceutical Science

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