Regenerative therapy for tendon and ligament disorders in horses: results of treatment with stemcells, blood products, scaffolds and growth factors – review of the literature and meta analysis

Abstract

ZusammenfassungHerkömmliche Behandlungsansätze bei Sehnen-und Banderkrankungen führen nach einer langen Heilungsphase zur Entstehung von funktionell minderwertigem Ersatzgewebe (Reparatur Regenerative therapy for tendon and ligament disorders in horses: results of treatment with stemcells, blood products, scaffolds and growth factors -review of the literature and meta analysis Conventional treatments for tendon and ligament disorders give rise to functionally inferior repair tissue within a relatively long healing phase which results in a relatively high recurrence rate. There is however increasing evidence that intralesional treatments with cells, blood products, scaffolds and biological factors such as growth factors have a regenerative effect. In the present review the principal scientific findings on the clinical effects in living horses of, for example, bone-marrow-derived and adipose-tissue-derived mesenchymal stromal cells (MSCs), embryonic stem cells (ESCs) and blood products such as PRP (platelet rich plasma), ACP (autologous conditioned plasma) and ACS (autologous conditioned serum) are summarized and discussed. Relating to horses, several scientific investigations with different study designs can be found in the literature: 1) Clinical case series, which allow a limited comparison of different treatment methods on the basis of the resulting recurrence rate. 2) Experimental animal studies on controlled artificial tendon defects, which often provide detailed results on the histological, biochemical and biomechanical quality of repair tissue. 3) Single placebo-controlled studies of naturally occurring tendinopathies which should, at least theoretically, provide the highest degree of evidence, however show methodological weaknesses in many cases. Among other aspects, the advantages and disadvantages of the various substrates, their biological safety, their effect with regard to the structural and biomechanical properties of different tendons and ligaments and their effect on the recurrence rate of tendon and ligament disorders are described and discussed. There is increasing evidence that substrates with regenerative potential are superior to other, i.e. conventional, treatments although it is still not clear which product or combination of substrates is most appropriate in individual cases.

The Use of Platelet-Rich Plasma for Treatment of Tenodesmic Lesions in Horses: A Systematic Review and Meta-Analysis of Clinical and Experimental Data

“…Differently from recent human and veterinary reviews [15,22,23,[25][26][27]64], both in vivo and in vitro investigations were included in this study. Tendon and ligament explants cultured in PRP showed enhanced expression of matrix protein and growth factors with no concomitant increase in the catabolic molecules.…”

“…Some studies [23,35,50,54,55] (study ID in Table 1: 10, 11, 16, 23, 24) selected horses from the patients referred to respective hospitals, while other trials do not specify the selection process. The age, sex, breed, and aptitude of the horses selected for the investigations differ in the same study and between different studies.…”

“…Platelet concentrate has been tested on tendons in nine trials [23,30,31,40,44,45,47,48,51] (study ID in Table 1: 4-6, 9, 11, 12, 14, 17, 21), on ligaments in five experiments [35,39,41,54] (study ID in Table 1: 10, 20, 22, 23), and on both structures in two studies [3,38] (study ID in Table 1: 3, 13).…”

“…Systematic PRP evaluation for repairing tendon and ligament injuries may provide a scientific reference for treatment and clinical application strategies. Indeed, although in human and veterinary medicine several systematic reviews and meta-analyses have been subsequently published [3,15,[21][22][23][24][25][26][27][28][29], it is still not clear which product or combination of substrates is most appropriate related to individual cases. Due to the variety of lesions and products, clinical studies would require large numbers, with economic and ethical concerns [30][31][32].…”