Rising Stars in Veterinary Regenerative Medicine: 2022

In equine medicine, the use of regenerative therapeutics has gained growing attention, but is still a new and complex field with room for improvement. Platelet lysate (PL) can be used as therapeutic agent but is also a promising supplement for the culture of multipotent mesenchymal stromal cells. To enable a targeted use of PL both in clinic and laboratory, it is crucial to learn more details on its effective ingredients. While so far, mainly growth factor components have been analyzed in platelet-based products such as PL, the current study focuses on the content of cytokines in serum, plasma, platelet concentrate and PL. Blood was harvested from 20 clinically healthy horses and subjected to blood count and chemistry analysis, as well as to further processing to PL. Plasma and platelet concentrate were produced by a buffy-coat-based method and PL was produced from the concentrate by freeze-thawing. Samples from each horse were analyzed regarding interleukin (IL)-1β, −4, −6 and −10, interferon-γ and tumor necrosis factor-α concentrations using sandwich ELISAs. Cytokine concentrations in serum, plasma, concentrate and PL were similar and correlated significantly. However, there was a large inter-individual variability in cytokine concentrations between the different donor horses. The samples from some donor animals had overall very high cytokine concentrations, while samples from other donors had no measurable cytokine ingredient. This pattern was observed for all cytokines. There was a noticeable link between high cytokine concentrations in the blood products and abnormal findings in blood chemistry. Cytokine concentrations in samples from horses with abnormal findings were significantly higher than in samples from the remaining horses. The interindividual differences in cytokine concentrations could be highly relevant when using PL for therapy and cell culture, as the mode of action of the PL is likely changed depending on the presence of pro- and anti-inflammatory cytokines. Blood chemistry might be useful to predict cytokine concentrations in blood products.

Osteoarthritis (OA) is a degenerative disease that eventually leads to the complete degradation of articular cartilage. Articular cartilage has limited intrinsic capacity for self-repair and, to date, there is no curative treatment for OA. Humans and horses have a similar articular cartilage and OA etiology. Thus, in the context of a One Health approach, progress in the treatment of equine OA can help improve horse health and can also constitute preclinical studies for human medicine. Furthermore, equine OA affects horse welfare and leads to significant financial losses in the equine industry. In the last few years, the immunomodulatory and cartilage regenerative potentials of mesenchymal stromal cells (MSCs) have been demonstrated, but have also raised several concerns. However, most of MSC therapeutic properties are contained in their secretome, particularly in their extracellular vesicles (EVs), a promising avenue for acellular therapy. From tissue origin to in vitro culture methods, various aspects must be taken into consideration to optimize MSC secretome potential for OA treatment. Immunomodulatory and regenerative properties of MSCs can also be enhanced by recreating a pro-inflammatory environment to mimic an in vivo pathological setting, but more unusual methods also deserve to be investigated. Altogether, these strategies hold substantial potential for the development of MSC secretome-based therapies suitable for OA management. The aim of this mini review is to survey the most recent advances on MSC secretome research with regard to equine OA.