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The Results of Using Stem Cells to Treat Flexor Tendonitis
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Rationale behind the use of exogenous stem cells to treat tendon over-strain injuries
Tendon naturally heals (repairs) well but the scar tissue formed in this repair is functionally deficient compared to normal tendon, which has important consequences for the animal in terms of reduced performance and a substantial risk of re-injury, in spite of a multitude of treatments that have been proposed. As pain is not usually a feature of these conditions in the long-term, the primary need is to restore functionality and so this has encouraged the development of regenerative strategies. We have hypothesised that the implantation of autologous mesenchymal stem cells, in far greater numbers than are present normally within tendon tissue, would have the potential of regenerating or improving the repair of the tendon.
The equine digital flexor tendon strain injury provides many of the elements required for tendon tissue engineering – the lesion manifests within the central core of the tissue thus providing a natural enclosure for implantation and, by the time of stem cell implantation, is filled with granulation tissue which acts in the role of a scaffold. It has the added advantage of being highly vascularised and therefore capable of nutritional support of the implanted stem cells. The cytokine and mechanical environment, which are potentially important drives for differentiation, is provided by the intra-tendinous location of the cells and the suspension of MSCs in bone marrow supernatant which has been shown to have significant anabolic effects on cultures of equine ligament-derived cells.
Technique
BM-MSCs are still the most investigated and characterised post-natally derived stem cell as they appear to perform superiorly to MSCs recovered from other tissues in terms of differentiation into known cell types. Bone marrow is recovered from the sternum (or tuber coxae) under standing sedation and transferred to a laboratory in specially designed containers for culture and expansion of MSCs. Separation is largely dependent on the MSC’s property of adhesion to culture plastic which produces an enriched rather than pure cell preparation. As with other species, the presence of stem cells within equine MSC preparations has been shown by differentiating the cells along multiple cell lines using defined media (e.g. usually osteogenic, adipogenic and chondrogenic). After approximately 3 weeks, the cultured cells are transferred back to the veterinarian (10-50x106 cells, depending on the extent of the lesion) and implanted into the damaged tendon of the same horse under ultrasound guidance. The cells are suspended in bone marrow supernatant for implantation so that no ‘foreign’ material is implanted and to gain potential beneficial effects of the rich mix of growth factors present in the supernatant. After implantation, the limb is bandaged and the horses undergo a week of box rest to allow the cells to ‘take up residence in the tissue’. Thereafter the horses enter a controlled exercise programme for up to 48 weeks. This procedure has now become routine in equine clinical practice in many countries world-wide. Training course have been run to educate veterinarians on the technology, criteria for treatment and the practicalities of the technique to minimise inappropriate use. [...]
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