Therapeutic mesenchymal stromal stem cells: Isolation, characterization and role in equine regenerative medicine and metabolic disorders.

Mesenchymal stromal cells (MSC) have become a popular treatment modality in equine orthopaedics. Regenerative therapies are especially interesting for pathologies like complicated tendinopathies of the distal limb, osteoarthritis, osteochondritis dissecans (OCD) and more recently metabolic disorders. Main sources for MSC harvesting in the horse are bone marrow, adipose tissue and umbilical cord blood. While the acquisition of umbilical cord blood is fairly easy and non-invasive, extraction of bone marrow and adipose tissue requires more invasive techniques. Characterization of the stem cells as a result of any isolation method, is also a crucial step for the confirmation of the cells' stemness properties; thus, three main characteristics must be fulfilled by these cells, namely: adherence, expression of a series of well-defined differentiation clusters as well as pluripotency. EVs, resulting from the paracrine action of MSCs, also play a key role in the therapeutic mechanisms mediated by stem cells; MSC-EVs are thus largely implicated in the regulation of proliferation, maturation, polarization and migration of various target cells. Evidence that EVs alone represent a complex network 0involving different soluble factors and could then reflect biophysical characteristics of parent cells has fuelled the importance of developing highly specific techniques for their isolation and analysis. All these aspects related to the functional and technical understanding of MSCs will be discussed and summarized in this review.