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

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 more than 80% of chronic lameness in horses. Effective treatments are not available and developing them is of utmost importance. For this purpose, stem cell therapy in under investigation. Induced pluripotent stem cells (iPSCs) are obtained by ‘reprogramming’ adult cells into pluripotent stem cells that resemble those in the embryo. These iPSCs can provide unlimited cells for therapy with ability to differentiate into almost any type of cell, while no carrying ethical concerns. However, pre-clinical knowledge is limited to small animals (rodents and rabbits) with low translational potential, as their anatomy and biomechanics differ from those in human. Larger species such as the horse better resembles human joint’s features and can also benefit from these therapies, since they are also veterinary patients (One Medicine). To develop this approach, the first mandatory step is obtaining suitable cartilage from equine iPSCs, but we still lack critical knowledge on the biology of these cells and their differentiation process into cartilage (chondrogenesis). Thus, the overall goal of CAREQiPSC is to examine approaches to obtaining cartilage from equine iPSCs and to explore its therapeutic potential, as a necessary step to advance osteoarthritis treatments for both equines and humans. There are four specific goals that underpin this objective: 1) Establishing equine iPSCs from new types of equine cells that may retain higher chondrogeneic ‘memory’. Cord blood cells and articular chondrocytes were initially selected, based on findings in human iPSCs. 2) Deriving mesenchymal-like cells as an intermediate population between equine iPSCs and chondrocytes. 3) Comparing the chondrogeneic ability of these mesenchymal cells under different in vitro three-dimensional culture systems that are designed to promote their differentiation. 4) Exploring the therapeutic potential of the cells in an ex vivo cartilage explant system. Two main conclusions have been obtained, providing evidence for the first time about: 1) Equine iPSCs can be generated more efficiently from cells of early developmental stages, which show higher proliferation and higher expression of pluripotent markers. 2) Chondrogenesis of equine iPSCs can be induced following different pathways, yet protocols require further fine-tuning to be adapted to the equine species.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз