Optimal management of tendon overuse injuries in equine and human athletes should avoid the formation of excessive scar tissue, regenerate normal tendon matrix, and reduce re-injury rates. We hypothesized that the implantation of marrow-derived stromal stem cells (BM-MSCs), in far greater numbers than are present normally within tendon tissue, would synthesize a matrix more closely resembling tendon matrix than scar tissue, and hence increase the capacity to return to performance successfully. This article reviews the technique used clinically in the horse and the current outcome data for horses treated by the autologous implantation of BM-MSCs into moderate to severe acute superficial digital flexor tendon (SDFT) injuries. Bone marrow was aspirated from the sternum under standing sedation. The nucleated adherent cell population (containing the BM-MSCs) were isolated and expanded so that, after approximately three weeks, the cells were re-suspended in the supernatant from the bone marrow and implanted into injured SDFT under ultrasonographic guidance. The horses then entered a 48-week rehabilitation period consisting of an ascending exercise regime. By September 2006, 168 racehorses had undergone this regimen. For horses which had returned to full work, 18% had re-injured, which compared favourably to previous studies on conventional management (56% re-injury rate). No adverse effects were noted other than needle tracts visible ultrasonographically. Autologous implantation of mesenchymal stem cells into tendon injuries may therefore improve clinical outcome although definitive proof of efficacy, which is still lacking, will require randomized controlled trials.
1 December 2002 in Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology
Strain induced tendon or ligament injuries are an all too common consequence of athletic endeavour in both horses1 and humans,2–4 resulting in high morbidity and often compromising a return to the same level of activity.
There is a paucity of data regarding molecular markers that identify the phenotype of the tendon cell. This study aims to quantify gene expression markers that distinguish between tendon fibroblasts and other mesenchymal cells which may be used to investigate tenogenesis.
Introduction: Autologous mesenchymal stem cell (MSC) injection into naturally-occurring equine tendon injuries has been shown to be safe and efficacious and protocols inform translation of the technique into humans. Efficient transfer of cells from the laboratory into tissue requires well-validated transport and implantation techniques. Methods: Cell viability in a range of media was determined over 72 hours and after injection through a 19G, 21G or 23G needle. Viability, proliferation and apoptosis were analysed using TrypanBlue, alamarBlue® and AnnexinV assays. Results: Cell viability was similar in all re-suspension media following 24 hour storage, however cell death was most rapid in bone marrow aspirate, platelet-rich plasma and serum after longer storage. Cryogenic media exhibited greatest viability regardless of storage time. Cell proliferation after 24 and 72 hour storage was similar for all media, except after 24 hours in serum wherein proliferation was enhanced. MSC tri-lineage differentiation and viability did not significantly change when extruded through 19G, 21G or 23G needles, but 21G and 23G needles significantly increased apoptotic cells compared to 19G and non-injected controls. All gauges induced a decrease in metabolic activity immediately post-injection but cells recovered by 2 hours. Conclusions: These data indicate storage and injection influence viability and subsequent cell behaviour and provide recommendations for MSC therapy that implantation of cells should occur within 24 hours of recovery from culture, using larger needle bores.