Tenogenically Induced Allogeneic Peripheral Blood Mesenchymal Stem Cells in Allogeneic Platelet-Rich Plasma: 2-Year Follow-up after Tendon or Ligament Treatment in Horses

Abstract

Poor healing of tendon and ligament lesions often results in early retirement of sport horses. Therefore, regenerative therapies are being explored as potentially promising treatment for these injuries. In this study, an intralesional injection was performed with allogeneic tenogenically induced mesenchymal stem cells and platelet-rich plasma 5–6 days after diagnosis of suspensory ligament (SL) (n = 68) or superficial digital flexor tendon (SDFT) (n = 36) lesion. Clinical, lameness and ultrasonographic evaluation was performed at 6 and 12 weeks. Moreover, a survey was performed 12 and 24 months after treatment to determine how many horses were competing at original level and how many were re-injured. At 6 weeks, 88.2% of SL (n = 68) and 97.3% of SDFT lesions (n = 36) demonstrated moderate ultrasonographic improvement. At 12 weeks, 93.1% of SL (n = 29) and 95.5% of SDFT lesions (n = 22) improved convincingly. Moreover, lameness was abolished in 78.6% of SL (n = 28) and 85.7% (n = 7) of SDFT horses at 12 weeks. After 12 months (n = 92), 11.8% of SL and 12.5% of SDFT horses were re-injured, whereas 83.8 of SL and 79.2% of SDFT returned to previous performance level. At 24 months (n = 89) after treatment, 82.4 (SL) and 85.7% (SDFT) of the horses returned to previous level of performance. A meta-analysis was performed on relevant published evidence evaluating re-injury 24 months after stem cell-based [17.6% of the SL and 14.3% of the SDFT group (n = 89)] versus conventional therapies. Cell therapies resulted in a significantly lower re-injury rate of 18% [95% confidence interval (CI), 0.11–0.25] 2 years after treatment compared to the 44% re-injury rate with conventional treatments (95% CI, 0.37–0.51) based on literature data (P < 0.0001).

The Use of Peripheral Blood-Derived Stem Cells for Cartilage Repair and Regeneration In Vivo: A Review

“…Pitchford et al found, that MSCs/CFU-F were not found in mice PB post-mobilization with G-CSF, but when adding vascular endothelial growth factor and CXCR4-antagonist (Pitchford et al, 2009). Spaas et al systematically studied the isolation and culture methods, cell characteristics, and clinical safety of equine PB-MSCs, and applied them to many veterinary clinical studies, such as promoting cartilage repair, cutaneous wound healing, and healing of tendon and ligament lesions (Spaas et al, 2013;Beerts et al, 2017;Martinello et al, 2018;Broeckx et al, 2019a). Allogenic or xenogeneic MSCs banks, improving the mobilization and purification techniques, and shortening the culture cycle might effectively account for deficiencies in autologous MSCs, reduce the burden on both patients and treatment providers, and promote the development of singlestage procedures (Moroni and Fornasari, 2013;Pescador et al, 2017).…”

Equine Fetal, Adult, and Embryonic Stem Cell-Derived Tenocytes Are All Immune Privileged but Exhibit Different Immune Suppressive Properties In Vitro

“…Although allogeneic tendon tissue transplantations are carried out in humans [11], they require decellularization to remove the immune cells within the tissue to prevent an immune response [12]. Tendon-derived stem cells have been shown to be nonimmunogenic in vitro [60] and in vivo [61,62], and MSCs stimulated to differentiate toward teno-cytes have been successfully used in allogeneic transplantations in horses [63]. However, to our knowledge, there are no reports on the immune properties of tenocytes isolated from tendon tissue.…”

Mesenchymal stem cell: Basic research and potential applications in cattle and buffalo

“…Use of MSCs in various animal species (canine and equine) have shown improved results in affections of muscle, tendon, ligament or bone injuries (Beerts et al, 2017;Brown, Harman, & Black, 2012;Canapp, Leasure, Cox, Ibrahim, & Carr, 2016;Case, Palmer, Valdes-Martinez, Egger, & Haussler, 2013;Gibson, Brown, & Brown, 2017;Leppanen, Heikkilä, Katiskalahti, & Tulamo, 2009). As in vitro studies confirm b-/buf-MSCs potential to transdifferentiate into myocytes and osteocytes, the cells may be used to treat the conditions.…”