CAREQiPSC aims at providing critical knowledge to facilitate in vivo application of iPSCs in the horse to treat osteoarthritis, which will both advance the veterinary field and will generate preclinical information transferable to human therapy. Osteoarthritis affects more than 303 million people worldwide and constitutes the single most common cause of disability in older adults, representing a huge socio-economic burden associated with reduced life quality and direct and indirect estimated costs greater than €11,000 annually per patient. In horses, osteoarthritis is responsible for up to 83.5% of chronic lameness. Due to the main use of these animals in sports, such pathology constitutes an important burden for the equine industry, which has an annual economic impact in Europe of over €100 billion, with an additional turnover of >€25 billion in horseracing betting. Actually, the equine sports and leisure market in Europe is the largest in the world and promotes EU regional sustainable growth.
Therefore, the lack of effective treatments for osteoarthritis is a timely issue that has led to interest in stem cell therapies, of which iPSCs hold great promise as they can provide an ethical and unlimited source of chondrocytes for cartilage repair. However, this is a new field with many challenges yet to face. While in vitro experiments and in vivo studies in rodents have provided valuable knowledge, further pre-clinical research in large animals is critical for clinical translation. The horse is both a highly valuable model and a potential beneficiary as patient, but very little progress has been made in obtaining cartilage from equine iPSCs.
This project provides fundamental knowledge to advance in this direction and facilitate human translation by using a Comparative Medicine approach. Specifically, different types of equine cells have been barely compared to obtain iPSCs, and there are no reports comparing pre-natal, peri-natal and adult equine cells. In fact, the equine parental cells covered by this project have not been explored before. Furthermore, there is not a clearly superior protocol for reprogramming equine iPSCs and this project helps developing more consistent and repeatable methodologies. Cartilage derivation from equine iPSCs has not been consistently reported, so assessing different methodologies and characterising the cartilage obtained facilitates establishing suitable protocols to promote the chondrogenesis of these cells, which is fundamental for both pre-clinical and clinical application. In this way, equine and human medicine are both advanced by helping each other under an innovative One Medicine approach.