Industrial Development of Standardized Fetal Progenitor Cell Therapy for Tendon Regenerative Medicine: Preliminary Safety in Xenogeneic Transplantation
Alexis Laurent,
Philippe Abdel-Sayed,
Anthony Grognuz,
Corinne Scaletta,
Nathalie Hirt-Burri,
Murielle Michetti,
Anthony S. de Buys Roessingh,
Wassim Raffoul,
Peter Kronen,
Katja Nuss,
Brigitte von Rechenberg,
Lee Ann Applegate,
Salim E. Darwiche
Affiliations
Alexis Laurent
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Épalinges, Switzerland
Philippe Abdel-Sayed
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Épalinges, Switzerland
Anthony Grognuz
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Épalinges, Switzerland
Corinne Scaletta
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Épalinges, Switzerland
Nathalie Hirt-Burri
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Épalinges, Switzerland
Murielle Michetti
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Épalinges, Switzerland
Anthony S. de Buys Roessingh
Children and Adolescent Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland
Wassim Raffoul
Plastic, Reconstructive, and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland
Peter Kronen
Musculoskeletal Research Unit, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, Switzerland
Katja Nuss
Musculoskeletal Research Unit, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, Switzerland
Brigitte von Rechenberg
Musculoskeletal Research Unit, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, Switzerland
Lee Ann Applegate
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Épalinges, Switzerland
Salim E. Darwiche
Musculoskeletal Research Unit, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, Switzerland
Tendon defects require multimodal therapeutic management over extensive periods and incur high collateral burden with frequent functional losses. Specific cell therapies have recently been developed in parallel to surgical techniques for managing acute and degenerative tendon tissue affections, to optimally stimulate resurgence of structure and function. Cultured primary human fetal progenitor tenocytes (hFPT) have been preliminarily considered for allogeneic homologous cell therapies, and have been characterized as stable, consistent, and sustainable cell sources in vitro. Herein, optimized therapeutic cell sourcing from a single organ donation, industrial transposition of multi-tiered progenitor cell banking, and preliminary preclinical safety of an established hFPT cell source (i.e., FE002-Ten cell type) were investigated. Results underlined high robustness of FE002-Ten hFPTs and suitability for sustainable manufacturing upscaling within optimized biobanking workflows. Absence of toxicity or tumorigenicity of hFPTs was demonstrated in ovo and in vitro, respectively. Furthermore, a 6-week pilot good laboratory practice (GLP) safety study using a rabbit patellar tendon partial-thickness defect model preliminarily confirmed preclinical safety of hFPT-based standardized transplants, wherein no immune reactions, product rejection, or tumour formation were observed. Such results strengthen the rationale of the multimodal Swiss fetal progenitor cell transplantation program and prompt further investigation around such cell sources in preclinical and clinical settings for musculoskeletal regenerative medicine.
