Effects of in vivo applications of peripheral blood‐derived mesenchymal stromal cells (PB‐MSCs) and platlet‐rich plasma (PRP) on experimentally injured deep digital flexor tendons of sheep

Abstract

Tendon injuries, degenerative tendinopathies, and overuse tendinitis are common in races horses. Novel therapies aim to restore tendon functionality by means of cell-based therapy, growth factor delivery, and tissue engineering approaches. This study examined the use of autologous mesenchymal stromal cells derived from peripheral blood (PB-MSCs), platelet-rich plasma (PRP) and a combination of both for ameliorating experimental lesions on deep digital flexor tendons (DDFT) of Bergamasca sheep. In particular, testing the combination of blood-derived MSCs and PRP in an experimental animal model represents one of the few studies exploring a putative synergistic action of these treatments. Effectiveness of treatments was evaluated at 30 and 120 days comparing clinical, ultrasonographic, and histological features together with immunohistochemical expression of collagen types 1 and 3, and cartilage oligomeric matrix protein (COMP). Significant differences were found between treated groups and their corresponding controls (placebo) regarding tendon morphology and extracellular matrix (ECM) composition. However, our results indicate that the combined use of PRP and MSCs did not produce an additive or synergistic regenerative response and highlighted the predominant effect of MSCs on tendon healing, enhanced tissue remodeling and improved structural organization. ß

Biomaterials for Tendon/Ligament and Skin Regeneration

“…Similar results were also observed using PRP with tendon-derived stem cells (TDSCs) [2]. However, in a sheep model, no differences were observed between the PRP group and PRP-stem cell group [3]. This approach is highly translational, since both autologous stem cells and PRP can be obtained from the same patients.…”

CORR® ORS Richard A. Brand Award for Outstanding Orthopaedic Research: Engineering Flexor Tendon Repair With Lubricant, Cells, and Cytokines in a Canine Model

“…Second, we did not test either the cell-based therapy or surface modification alone. However, some studies have shown that bone marrow stromal cells do increase tendon healing capacity [8,10,15], and others have shown that surface modification decreases tendon adhesions [14,40]. Therefore, the purposes of our study were to investigate the effects of combining these treatments on postoperative adhesion formation and tendon healing.…”

Tendon healing induced by chemically modified mRNAs

“…Because only early time points were investigated, it might be too early to draw final conclusion whether cmRNA hBMP-7 positively impacts physiological regeneration of tendons. Studies from other authors reported significant changes of collagen type I content and morphological changes towards regeneration as early as weeks or months post injury (Martinello et al, 2013). To finally answer the question, whether overexpression of hBMP-7 leads to increased content of collagen type I, further long term studies have to be conducted with examinations of the tendons at later time points.…”

“…As surgically injured rat tendons did not resemble these conditions, we additionally investigated cmRNA transfection efficacy in a large animal model of acute tendinopathy. Collagenase has already been used to generate tendon defects in sheep (Martinello et al, 2013). However, those defects do not closely resemble the morphology of acute tendon defects as seen in the clinics, as resulting inflammation and tissue destruction are distributed over the entire tendon.…”

“…Furthermore, physical methods, such as electromagnetic stimulation or shockwave therapy (Bosch et al, 2010;Seeliger et al, 2014) are also used. Also, various approaches using stem cell-based (Martinello et al, 2013;Renzi et al, 2013;Smith, 2008) and growth factor-based therapies have been investigated (Arguelles et al, 2008;Shah et al, 2013;Witte et al, 2011).…”