Mesenchymal stem cells (MSCs) and their therapeutic properties

Treatment

Stem cells can be used for advanced therapies to enhance tissue or organ repair by harnessing the body’s own mechanisms. Among the different types of stem cells, mesenchymal stem cells (MSCs) are one of the most prominent types for therapy. These are adult multipotent stem cells that can be found in a wide variety of tissues in the horse, including bone marrow, adipose tissue, muscle, periosteum and peripheral blood, among many others.

MSCs exert their therapeutic function through several mechanisms: on the one hand, they can integrate into the tissue to replace damaged cells and produce extracellular matrix. On the other hand, they also have a trophic effect mediated by the secretion of a variety of mediators to limit cell damage and promote cell proliferation, as well as an anti-fibrotic effect that can improve the quality of the repaired tissue. Nevertheless, MSC main therapeutic mechanism is through their immunomodulatory and anti-inflammatory capacities. Such properties are making them particularly relevant in current research to develop new therapies. Using these mechanisms, the use of MSCs in regenerative medicine aims to restore or re-establish the normal structure and function of tissues lost as a result of disease, injury or age-related degeneration.

The role of MSCs in regenerative therapy

Treatment with MSCs can be carried out with cells from the same patient (autologous origin) or from a donor of the same species (allogeneic origin). However, treatment with autologous cells is not always possible because the quality of MSCs may be impaired in some individuals due to certain diseases or related to advance age. As a result, the therapeutic properties of these MSCs may be affected and not be suitable for therapy. In addition, certain treatments require large numbers of MSCs, which must be expanded in vitro and characterised to ensure their cell lineage before implantation. This process takes up to several weeks, delaying the delivery of the therapy. For these reasons, treatment with allogeneic cells obtained from healthy donors, previously characterised, quality-assured and stored in cell banks is a great advantage.

The importance of MSC haplotype for MHC I, II and III

Recent research into immune response of the patient against donor’s MSCs highlights the importance of using compatible allogeneic stem cells to increase the chances of success and improve safety. Compatibility between donor and recipient depends to a large extent on the degree of similarity between the molecules of the well-known major histocompatibility complex (MHC), which are expressed in the cell surface or present in a soluble form. The haplotype for MHC-I, II and III can be analysed to ensure similarity between donor and recipient MHC. The MHC haplotype refers to the set of genes that encode these molecules and that for genetic reasons (their close location on the chromosome) tend to be inherited together, i.e. as a group. Each parent contributes one haplotype (a group of genes) to their offspring, so that all individuals end up having two haplotypes, one inherited from the father and the other one from the mother.
Our research group has extensive experience in equine haplotyping for MHC I, II and III. Using a small blood sample we study 10 markers, known as microsatellite markers, to determine which MSCs from our stem cell bank would be compatible with the equine patient. However, to date, more than 500 equine MHC haplotypes have been described in various breeds, which makes it very difficult to find a donor completely matching with the patient. Therefore, our goal is to identify the most frequent haplotypes among the main breeds in Spain (Purebred Spanish Horse, Purebred Arabian and Spanish Sport Horse) and to create a bank with equine MSCs carrying the most common MHC haplotypes to facilitate finding such compatibilities. Our final goal is to provide researchers, veterinary practitioners, and biotech/pharma companies with well-characterised cells to advance research into regenerative cell therapies.