INTRODUCTION
Tendon disorders compromise pain-free activity and often progress to chronic pain with a major impact on quality of life. Achilles tendinopathy (AT) is particularly common with many proposed therapies.
However, apart from eccentric loading exercises, none have been shown to be more effective than placebo[1]. Even the recent popular use of platelet-rich plasma has shown poor efficacy [2, 3]. There is therefore a clear need for new effective non-surgical treatments. Mesenchymal stem cells (MSCs) offer the potential for tendon regeneration and improved functional outcome via either direct or paracrine effects. We have therefore investigated the efficacy of bone marrow-derived MSCs (BM-MSCs) implanted into naturally-occurring over-strain injury of the equine superficial digital flexor tendon (SDFT), a commonly-injured weight-bearing tendon with many similarities to human AT. We hypothesised that autologous implanted MSCs would survive in the tendon and induce normalization of the tendon matrix and reduce re-injury rates.
METHODS
Labelling MSCs with technetium99m linked to HMPAO enabled non-invasive monitoring of cell fate in clinical cases (n=13).
This revealed high initial cell loss (~75% over 24 hours).
Longer term labelling with a fluorescent cytoplasmic dye showed the retention of small numbers of labelled cells for up to 5 months, similar to that reported for shorter term studies[4, 5].
RESULTS
In a controlled experimental study of naturally-occurring SDFT injuries (n=12), MSC-treated tendons had greater elasticity, reduced cross-sectional area, and cellularity, improved organisational scores, and lower GAG content compared to saline-treated tendons, although not all parameters were statistically significant.
In 113 treated racehorses, the re-injury percentage was 27.4%, which was significantly less than published for racehorses treated in other ways (p<0.05 versus 56%[6]; p<0.01 versus 50%[7]).
These findings in a large animal model of naturally-occurring tendinopathy provide supportive evidence for the efficacy and safety for the use of MSCs for the treatment of tendinopathy in humans.
ACKNOWLEDGEMENTS: Horserace Betting Levy Board, Japan Racing Association and Quy Bioscience Ltd (trading as VetCell).
REFERENCES:
1. Magnussen, R.A., W.R. Dunn, and A.B. Thomson, Nonoperative treatment of midportion Achilles tendinopathy: a systematic review. Clin J Sport Med, 2009. 19(1): p. 54-64.
2. de Vos, R.J., et al., Platelet-rich plasma injection for chronic Achilles tendinopathy: a randomized controlled trial. JAMA, 2010. 303(2): p. 144-9.
3. de Vos, R.J., et al., No effects of PRP on ultrasonographic tendon structure and neovascularisation in chronic midportion Achilles tendinopathy. Br J Sports Med, 2011. 45(5): p. 387-92.
4. Guest, D.J., M.R. Smith, and W.R. Allen, Monitoring the fate of autologous and allogeneic mesenchymal progenitor cells injected into the superficial digital flexor tendon of horses: preliminary study. Equine Vet J, 2008. 40(2): p. 178-81.
5. Guest, D.J., M.R. Smith, and W.R. Allen, Equine embryonic stem-like cells and mesenchymal stromal cells have different survival rates and migration patterns following their injection into damaged superficial digital flexor tendon. Equine Vet J, 2010. 42(7): p. 636-42.
6. Dyson, S.J., Medical management of superficial digital flexor tendonitis: a comparative study in 219 horses (1992-2000). Equine Vet J, 2004. 36(5): p. 415-9.
7. O'Meara, B., et al., An investigation of the relationship between race performance and superficial digital flexor tendonitis in the Thoroughbred racehorse. Equine Vet J, 2010. 42(4): p. 322-6.
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