Autologous and Allogeneic Cytotherapies for Large Knee (Osteo)Chondral Defects: Manufacturing Process Benchmarking and Parallel Functional Qualification
Virginie Philippe,
Annick Jeannerat,
Cédric Peneveyre,
Sandra Jaccoud,
Corinne Scaletta,
Nathalie Hirt-Burri,
Philippe Abdel-Sayed,
Wassim Raffoul,
Salim Darwiche,
Lee Ann Applegate,
Robin Martin,
Alexis Laurent
Affiliations
Virginie Philippe
Orthopedics and Traumatology Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland
Annick Jeannerat
Preclinical Research Department, LAM Biotechnologies SA, CH-1066 Epalinges, Switzerland
Cédric Peneveyre
Preclinical Research Department, LAM Biotechnologies SA, CH-1066 Epalinges, Switzerland
Sandra Jaccoud
Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
Corinne Scaletta
Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
Nathalie Hirt-Burri
Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
Philippe Abdel-Sayed
Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
Wassim Raffoul
Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
Salim Darwiche
Musculoskeletal Research Unit, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, Switzerland
Lee Ann Applegate
Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
Robin Martin
Orthopedics and Traumatology Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland
Alexis Laurent
Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
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.