Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic Transplantation
Alexis Laurent,
Philippe Abdel-Sayed,
Aurélie Ducrot,
Nathalie Hirt-Burri,
Corinne Scaletta,
Sandra Jaccoud,
Katja Nuss,
Anthony S. de Buys Roessingh,
Wassim Raffoul,
Dominique Pioletti,
Brigitte von Rechenberg,
Lee Ann Applegate,
Salim Darwiche
Affiliations
Alexis Laurent
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland
Philippe Abdel-Sayed
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland
Aurélie Ducrot
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland
Nathalie Hirt-Burri
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland
Corinne Scaletta
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland
Sandra Jaccoud
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland
Katja Nuss
Musculoskeletal Research Unit, Zurich Tierspital, University of Zurich, CH-8952 Schlieren, 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
Dominique Pioletti
Laboratory of Biomechanical Orthopedics, Ecole Polytechnique Fédérale de Lausanne, CH-2002 Neuchâtel, Switzerland
Brigitte von Rechenberg
Musculoskeletal Research Unit, Zurich Tierspital, University of Zurich, CH-8952 Schlieren, Switzerland
Lee Ann Applegate
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland
Salim Darwiche
Musculoskeletal Research Unit, Zurich Tierspital, University of Zurich, CH-8952 Schlieren, Switzerland
Diverse cell therapy approaches constitute prime developmental prospects for managing acute or degenerative cartilaginous tissue affections, synergistically complementing specific surgical solutions. Bone marrow stimulation (i.e., microfracture) remains a standard technique for cartilage repair promotion, despite incurring the adverse generation of fibrocartilagenous scar tissue, while matrix-induced autologous chondrocyte implantation (MACI) and alternative autologous cell-based approaches may partly circumvent this effect. Autologous chondrocytes remain standard cell sources, yet arrays of alternative therapeutic biologicals present great potential for regenerative medicine. Cultured human epiphyseal chondro-progenitors (hECP) were proposed as sustainable, safe, and stable candidates for chaperoning cartilage repair or regeneration. This study describes the development and industrial transposition of hECP multi-tiered cell banking following a single organ donation, as well as preliminary preclinical hECP safety. Optimized cell banking workflows were proposed, potentially generating millions of safe and sustainable therapeutic products. Furthermore, clinical hECP doses were characterized as non-toxic in a standardized chorioallantoic membrane model. Lastly, a MACI-like protocol, including hECPs, was applied in a three-month GLP pilot safety evaluation in a caprine model of full-thickness articular cartilage defect. The safety of hECP transplantation was highlighted in xenogeneic settings, along with confirmed needs for optimal cell delivery vehicles and implantation techniques favoring effective cartilage repair or regeneration.
