Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic Transplantation

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.