Cell therapy for tendinitis, experimental and clinical report

Abstract

To compare cultured bone marrow mesenchymal cells (cBMSC), bone marrow mononucleated cells (BMMNCs), and placebo to repair collagenase-induced tissue damage in an equine model of experimental tendonitis, 6 Standardbred horses with no signs of previous SDF tendon injury have been recruited. Three weeks after collagenase treatment an average of either 5.5 x 10(6) cBMSCs or 122.3 x 10(6) BMMNCs, saline solution (placebo) or fibrin glue were injected intralesionally in random order. Horses were stall rested for 21 weeks, and tendon ultrasound scans performed before and during this period. Horses were euthanized and tendons harvested for histology and immunohistochemistry. Data observed in this study showed effectiveness of cBMSC and BMMNC in regenerating tendon tissue after collagenase -induced tendonitis. Both cBMSC and BMMNC transplantation resulted in qualitatively similar regeneration of tendon extracellular matrix in terms of type I/III collagen ratio, fiber orientation, and COMP expression. After this favourable results, 20 horses were recruited referred for spontaneous lesions of the flexor tendons or the suspensory ligament. Horses were treated with autologous graft of BMMNCs.After treatment the. the exercise program allowed was 8 weeks stall rest, 4 weeks hand walking, 4 weeks trotting, 4 weeks of gradually raising of exercise level then horses were gone back to race. US characteristics of lesions started to improve at T3. CSA-l, FPS and TLS were better in all patients, with an appreciable filling of lesions indicated by a decreasing of CSA-l and increasing of TLS. When horses started the exercise program T8 tendon architecture improved, demonstrated by their longitudinal alignment and length. At T6, and persistently in later follow-up, no lameness was evident by clinical examination. At time of writing 12 patients (60%) were go back to races, while other 8 (40%) are under controlled exercise program. Re-injury rate was assessed at 25%. All the owners judged good to excellent the outcome in term of athletic success.

Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses

“…Several studies have tested the efficacy in tendon repair of cultured and expanded BMMNCs [20,21], whereas there are only two studies investigating the potential of freshly harvested and transplanted BMMNCs in promoting horse tendon healing, with interesting results [10,22]. In our study, the one-step BMMNC isolation was preferred, avoiding the laboratory culture expansion, that requires a three-week period and high costs.…”

Effect of the application of stem cells for tendon injuries in sporting horses

“…At the time of reporting, 12 subjects (60%) had returned to racing and 8 (40%) were training under a controlled exercise program. It was observed a recurrence of injury of 35%, and all owners rated the outcome (in terms of sporting success) from good to excellent (Lacitignola et al 2008).…”

“…(Kasashima et al 2011). Lacitignola et al (2008) conducted a study on cell therapy for tendinitis in horses with collagenase-induced tendinitis. In this study, the transplantation of MSCs derived from bone marrow produced regeneration of the extracellular matrix of tendons by enhancing the rates of production of collagen type I/III, and expression of COMP and improving fiber orientation.…”

Stem cell-based tissue engineering in veterinary orthopaedics

“…Furthermore, the effects of autologous bone marrowderived expanded MSC and bone marrow-derived mononuclear cells on tendon healing have been compared, revealing a similar improvement in both treatment groups compared to the control group, which was demonstrated by significantly improved ultrasonography and histology scores, higher COMP expressions and relatively lower type III collagen contents (Crovace et al 2007(Crovace et al , 2010Lacitignola et al 2008). …”