CAREQiPSC · Cartilage derived from equine induced pluripotent stem cells: an in vitro and ex vivo One Medicine approach for osteoarthritis

Osteoarthritis is a degenerative joint pathology that constitutes the first cause of disability in older adults and accounts for >80% of chronic lameness in horses. Effective treatments are not available while developing them is of utmost importance for the EU objective of translating knowledge into society’s benefit. Induced pluripotent stem cells (iPSCs) can provide unlimited cells for therapy with no ethical concerns. However, pre-clinical knowledge is limited to small animals with low translational potential. Larger species such as the horse better resembles human joint’s features and can also benefit from these therapies (One Medicine). To develop this approach, the first mandatory step is obtaining suitable cartilage from eqiPSCs. Thus, the goals of CAREQiPSC are: 1) establishing eqiPSCs from new sources with potential chondrogenic commitment, 2) derive mesenchymal-like cells with chondrogenic potential, 3) compare their chondrogenic ability under different conditions, 4) explore their therapeutic potential in an ex vivo cartilage explant system. To achieve these goals, eqiPSCs will be established from articular chondrocytes, umbilical cord mononuclear cells, and dermal fibroblasts, and their pluripotency will be studied. Mesenchymal cells derived from these lines will be characterised and induced to differentiate in the customary pellet system and in a 3D scaffold. The tissue obtained will be studied by histology, protein and gene expression, and its therapeutic potential will be investigated in cartilage explants, also including imaging and biomechanical assessment. The researcher’s previous experience in the equine model and the host’s expertise in iPSCs and infrastructure will ensure the achievement of these goals. The main outcome will be critical in vitro and ex vivo knowledge to facilitate in vivo application in the horse, which will generate preclinical information transferable to human therapy and will advance the veterinary medicine field.