Search

Abstract Low level laser therapy (LLLT) is frequently used in the treatment of wounds, soft tissue injury and in pain management. The exact penetration depth of LLLT in human tissue remains unspecified. Similar uncertainty regarding penetration depth arises in treating animals. This study was designed to test the hypothesis that transmission of LLLT in horses is increased by clipping the hair and/or by cleaning the area to be treated with alcohol, but is unaffected by coat colour. A LLLT probe (810 nm, 500 mW) was applied to the medial aspect of the superficial flexor tendon of seventeen equine forelimbs in vivo. A light sensor was applied to the lateral aspect, directly opposite the laser probe to measure the amount of light transmitted. Light transmission was not affected by individual horse, coat colour or leg. However, it was associated with leg condition (F = 4.42, p = 0.0032). Tendons clipped dry and clipped and cleaned with alcohol, were both associated with greater transmission of light than the unprepared state. Use of alcohol without clipping was not associated with an increase in light transmission. These results suggest that, when applying laser to a subcutaneous structure in the horse, the area should be clipped and cleaned beforehand.

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. [ABSTRACT FROM AUTHOR]

Background: In vivo measurement of limb stiffness and conformation provides a non-invasive proxy assessment of superficial digital flexor tendon (SDFT) and suspensory ligament (SL) function. Here, we compared it in fore and hindlimbs and after injury., Objectives: To compare the limb stiffness and conformation in forelimbs and hindlimbs, changes with age, and following injury to the SDFT and SL., Study Design: Retrospective cohort study., Methods: Limb stiffness was calculated using floor scales and an electrogoniometer taped to the dorsal fetlock. The fetlock angle and weight were simultaneously recorded five times with the limb weight-bearing and when the opposite limb was picked up (increased load). Limb stiffness of both limbs was calculated from the gradient of the regression line of angle versus load. Fetlock angle when the weight was zero was extrapolated from the graph and used as a measure of conformation. Limb stiffness was measured in uninjured forelimbs (n = 42 limbs), hindlimbs (n = 19 limbs), forelimbs with SDFT injury (n = 18) and hindlimbs with SL injury (n = 5)., Results: Limb stiffness correlated with weight in forelimbs as shown previously (p < 0.001) but also in hindlimbs (p = 0.006). When normalised to the horse's weight (503 kg, IQR 471.5-560), forelimb stiffness was significantly higher (22.3 [±4.5] × 10 -3 degree -1 ) than for the hindlimb (16.4 [±4.0] × 10 -3 degree -1 ; p < 0.001). While there were no significant differences between forelimb and hindlimb conformation in unaffected or SDFT injury, both limb stiffness and conformation was significantly greater in limbs with SL injury (p = 0.009 and p = 0.002, respectively)., Main Limitations: Small sample size, lack of clinical data including lameness and quantification of injuries., Conclusions: Injury to the forelimb SDFT does not alter limb stiffness or conformation in the long-term, while hindlimb SL injury simultaneously increases limb stiffness and fetlock angle, suggesting an increase in SL length following injury., (© 2024 The Author(s). Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Background: Desmitis of the accessory ligament of the deep digital flexor tendon (ALDDFT) is a commonly reported injury. Despite the commonality of this injury, the literature is limited to small case series, with the reported success following treatment varying from 18% to 75%., Objectives: To identify the prognosis and factors associated with a return to work following ALDDFT injury., Study Design: Retrospective case series., Methods: Medical records of horses from four equine hospitals (January 2000 and December 2018) with a diagnosis of desmitis of ALDDFT were reviewed. Data retrieved included case detail, use, history, lameness treatment and follow-up. Success was defined as returning to work. Backward stepwise logistic regression was used to identify variables significantly associated with return to work., Results: Ninety-one horses were included. The mean age was 13.5 years (standard deviation 4.9 years). Thirty-four percent (28/91) of horses were sound at the initial presentation. Sixty-eight percent (62/91) of horses were managed using controlled exercise alone, 28% (29/91) were treated with intra-lesional injection, therapeutic ultrasound, extracorporeal shockwave therapy or desmectomy of the ALDDFT and 3% (3/91) were euthanased without treatment. Sixty-four percent (54/85) of horses returned to work. Horses that were lame at follow-up were less likely to return to work (odds ratio [OR] 107.93, 95% confidence interval [CI] 20.06-580.61, p < 0.001) than those that returned to soundness. Identification of adhesions on ultrasonography was also associated with having reduced odds for return to work when compared to horses without adhesions (OR 0.10, 95% CI 0.01-0.76, p = 0.03)., Main Limitations: Retrospective nature of the study, the potential of selection bias with regards to follow-up., Conclusion: Sixty-four percent (54/85) of horses returned to work following injury of the ALDDFT. Persistence of lameness and adhesion formation were significantly associated with a poor outcome., (© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Tendinopathy is a common age-related disease which causes significant morbidity for both human athletes and performance horses. In the latter, the superficial digital flexor tendon is an excellent model for human tendinopathies because it is a functional homologue of the human Achilles tendon and a primary site of injuries with strong similarities to the human disease. Corticosteroids have been previously used clinically to treat tendinopathic inflammation, but they upregulate the p53-p21 axis with concomitant reductions in cell proliferation and collagen synthesis in human tenocytes. This phenotype is consistent with the induction of cellular senescence in vitro and in vivo and probably represents an important clinical barrier to their effective use. Because of the many differences in senescence mechanisms between species, this study aimed to evaluate these mechanisms after corticosteroid treatment in equine tenocytes. Exposure to clinically reflective levels of dexamethasone for 48 hours drove equine tenocytes into steroid induced senescence (SIS). This was characterised by permanent growth arrest and upregulation of p53, the cyclin dependent kinase inhibitors p21waf and p16ink4a as well as the matrix degrading enzymes MMP1, MMP2 and MMP13. SIS also induced a distinctive equine senescence associated secretory phenotype (eSASP) characterised by enhanced secretion of IL-8 and MCP-1. Preincubation with resveratrol or the potent SIRT1 activator SRT1720 prevented SIS in equine tenocytes, while treatment with the non-SIRT1 activating resveratrol analogue V29 was equally protective against SIS, consistent with a novel, as yet uncharacterised SIRT1-indendent mechanism which has relevance for the development of future preventative and therapeutic strategies., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Heidari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Achilles tendinopathy is a disabling condition that affects more than 50% of runners. Pre-clinical studies in a large animal model of naturally-occurring tendinopathy similar to human Achilles tendinopathy has shown benefits of autologous bone marrow-derived mesenchymal stem cell (MSC) implantation. However, MSCs are advanced therapies medicinal products (ATMPs), with strict regulatory requirements. Guided by the regulator we carried out a first in man study to assess the safety and efficacy of autologous MSC injection in human patients with non-insertional Achilles tendinopathy. Ten patients, mean age 47 with mid-portion Achilles tendon pain and swelling for more than 6 months, underwent autologous cultured cell injections (median 12.2 × 10 6 , range 5-19 × 10 6 cells) into their Achilles tendon. At 24 weeks follow-up, no serious adverse reactions or important medical events were observed. MOXFQ, EQ-5D-5L, and VISA-A scores improved clinically at 12 and 24 weeks. VAS pain improved increasingly at 6, 12 and 24 weeks. MOXFQ Pain and VISA-A Scores improved > 12 points from baseline to 24 weeks in 8 patients. Maximum anteroposterior tendon thickness as measured by greyscale US decreased by mean 0.8 mm at 24 weeks. This phase IIa study demonstrated the safety of autologous MSC injection for non-insertional Achilles tendinopathy and provides proof-of-concept of the technique in patients, all of whom had previously failed conservative treatments for chronic disease and leads the way for a larger randomised controlled trial., (© 2024. The Author(s).)

Resveratrol (RSV; trans-3,5,4'-trihydroxystilbene) strongly activates sirtuin 1, and it and its analogue V29 enhance the proliferation of mesenchymal stem/stromal cells (MSCs).Although culture medium containing 5-azacytydine and RSV inhibits senescence of adipose tissue-derived MSCs isolated from horses with metabolic syndrome, few studies have reported the effects of RSV on equine bone marrow-derived MSCs (eBMMSCs) isolated from horses without metabolic syndrome. The aim of this study was to investigate the effects of RSV and V29 on the cell cycle of eBMMSCs. Following treatment with 5 µM RSV or 10 µM V29, the cell proliferation capacity of eBMMSCs derived from seven horses was evaluated by EdU (5-ethynyl-2'-deoxyuridine) and Ki-67 antibody assays. Brightfield images of cells and immunofluorescent images of EdU, Ki-67, and DAPI staining were recorded by fluorescence microscopy, and the number of cells positive for each was quantified and compared by Friedman's test at P<0.05. The growth fraction of eBMMSCs was significantly increased by RSV and V29 as measured by the EdU assay (control 28.1% ± 13.8%, V29 31.8% ± 14.6%, RSV 32.0% ± 10.8%; mean ± SD; P<0.05) but not as measured by the Ki-67 antibody assay (control 27.0% ± 11.2%, V29 27.4% ± 10.8%, RSV 27.7% ± 6.8%). RSV and V29 promoted progression of the cell cycle of eBMMSCs into the S phase and may be useful for eBMMSC expansion., (©2023 The Japanese Society of Equine Science.)

Background: Oral and parenteral drug delivery in horses can be difficult. Equine-specific transdermal drug formulations offer improved ease of treatment; development of such formulations requires a deeper understanding of the structural and chemical tissue barrier of horse skin., Hypothesis/objectives: To compare the structural composition and barrier properties of equine skin., Animals: Six warmblood horses (two males, four females) with no skin diseases., Materials and Methods: Routine histological and microscopic analyses were carried out with image analysis for skin from six different anatomical locations. In vitro drug permeation was analysed using a standard Franz diffusion cell protocol coupled with reversed phase-high-performance liquid chromatography detailing flux, lag times and tissue partitioning ratios of two model drug compounds., Results: Epidermal and dermal thicknesses varied between sites. The dermal and epidermal thicknesses of the croup were 1764 ± 115 μm and 36 ± 3.6 μm, respectively, and were significantly different (p < 0.05) from the inner thigh thicknesses which were 824 ± 35 μm and 49 ± 3.6 μm. Follicular density and size also varied. The highest flux for the model hydrophilic molecule (caffeine) was for the flank (3.22 ± 0.36 μg/cm 2 /h), while that for the lipophilic molecule (ibuprofen) was for the inner thigh (0.12 ± 0.02 μg/cm 2 /h)., Conclusions and Clinical Relevance: Anatomical location differences in equine skin structure and small molecule permeability were demonstrated. These results can aid in the development of transdermal therapies for horses., (© 2023 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.)

Tendon injuries occur commonly in both human and equine athletes, and poor tendon regeneration leads to functionally deficient scar tissue and an increased frequency of re-injury. Despite evidence suggesting inadequate resolution of inflammation leads to fibrotic healing, our understanding of the inflammatory pathways implicated in tendinopathy remains poorly understood, meaning successful targeted treatments are lacking. Here, we demonstrate IL-1β, TNFα and IFN-γ work synergistically to induce greater detrimental consequences for equine tenocytes than when used individually. This includes altering tendon associated and matrix metalloproteinase gene expression and impairing the cells' ability to contract a 3-D collagen gel, a culture technique which more closely resembles the in vivo environment. Moreover, these adverse effects cannot be rescued by direct suppression of IL-1β using IL-1RA or factors produced by BM-MSCs. Furthermore, we provide evidence that NF-κB, but not JNK, P38 MAPK or STAT 1, is translocated to the nucleus and able to bind to DNA in tenocytes following TNFα and IL-1β stimulation, suggesting this signalling cascade may be responsible for the adverse downstream consequences of these inflammatory cytokines. We suggest a superior approach for treatment of tendinopathy may therefore be to target specific signalling pathways such as NF-κB., (© 2022. The Author(s).)

Evaluation of diagnostic anesthesia during equine lameness examination requires comparison of complex movement patterns and can be influenced by expectation bias. There is limited research about how changes in movement asymmetries after successful analgesia are affected by different exercise conditions. Movement asymmetry of head, withers and pelvis was quantified in N = 31 horses undergoing forelimb or hindlimb diagnostic anesthesia. Evaluation on a straight line and a circle was performed with subjective diagnostic anesthesia outcome and quantitative changes recorded. Mixed linear models (P < .05) analyzed the differences in movement asymmetry before/after diagnostic anesthesia - random factor: horse, fixed factors: surface (soft, hard), direction (straight, inside, outside, inside-outside average), diagnostic anesthesia outcome (negative, partially positive, positive) and two-way interactions. Forelimb diagnostic anesthesia influenced primary movement asymmetry (all head and withers parameters) and compensatory movement asymmetry (two pelvic parameters) either individually (P≤.009) or in interaction with surface (P≤.03). Hindlimb diagnostic anesthesia influenced primary movement asymmetry (all pelvic parameters) and compensatory movement asymmetry (two head and two withers parameters) either individually (P≤.04) or in interaction with surface (P≤.01;) or direction (P≤.006). Direction was also significant individually for two pelvic parameters (P≤.04). Changes in primary movement asymmetries after partially positive or positive outcomes indicated improvement in the blocked limb. Compensatory changes were mostly in agreement with the 'law of sides'. The changes were more pronounced on the hard surface for hindlimb lameness and on the soft surface for forelimb lameness. Withers asymmetry showed distinct patterns for forelimb and hindlimb lameness potentially aiding clinical decision-making., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Diagnostic analgesia and lunging are parts of the equine lameness examination, aiding veterinarians in localizing the anatomical region(s) causing pain-related movement deficits. Expectation bias of visual assessment and complex movement asymmetry changes in lame horses on the lunge highlight the need to investigate data-driven approaches for optimally integrating quantitative gait data into veterinary decision-making to remove bias. A retrospective analysis was conducted with inertial sensor movement symmetry data before/after diagnostic analgesia relative to subjective judgement of efficacy of diagnostic analgesia in 53 horses. Horses were trotted on the straight and on the lunge. Linear discriminant analysis (LDA) applied to ten movement asymmetry features quantified the accuracy of classifying negative, partial and complete responses to diagnostic analgesia and investigated the influence of movement direction and surface type on the quality of the data-driven separation between diagnostic analgesia categories. The contribution of movement asymmetry features to decision-making was also studied. Leave-one-out classification accuracy varied considerably (38.3-57.4% for forelimb and 36.1-56.1% for hindlimb diagnostic analgesia). The highest inter-category distances (best separation) were found with the blocked limb on the inside of the circle, on hard ground for forelimb diagnostic analgesia and on soft ground for hindlimb diagnostic analgesia. These exercises deserve special attention when consulting quantitative gait data in lame horses. Head and pelvic upward movement and withers minimum differences were the features with the highest weighting within the first canonical LDA function across exercises and forelimb and hindlimb diagnostic analgesia. This highlights that movement changes after diagnostic analgesia affect the whole upper body. Classification accuracies based on quantitative movement asymmetry changes indicate considerable overlap between subjective diagnostic analgesia categories.

Competing Interests: JI is employed by CVS Group plc. With the University of Liverpool, JI is the joint license holder for the LOAD client-reported outcomes measure. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Tendinopathy remains one of the most common musculoskeletal disorders affecting both human and equine athletes and presents a considerable therapeutic challenge. The following workshop report comes from the third Dorothy Havemeyer Symposium of Tendinopathy which provided a unique overview of our current understanding of both the basic science and the clinical challenges for diagnosing and treating tendinopathy in both species. Pathologically, tendon demonstrates alterations in both cellular, molecular, structural, and biomechanical features, leading to a spectrum of pathological endotypes. To develop novel interventions to manage, treat or prevent tendinopathies it is vital to understand the underlying mechanisms that lead to both tendon failure, and also regeneration and resolution of inflammation. The horse shows analogous pathology with both human Achilles tendinopathy (superficial digital flexor tendon) and intrathecal rotator cuff tears (deep digital flexor tendon tears) enabling scientists and clinicians from both medical and veterinary fields to work jointly on matching naturally occurring disease models. The experience in human medicine on the design, conduct, and impact of clinical trials has much to inform clinical trials in horses. There is a need to design appropriate studies to address clear questions, socialize the study to achieve good enrollment, and consider the significance and impact of the clinical question as well as the cost of addressing it. Because economics is often a limitation in equine medicine the use of observational studies, and specifically registries, should be given careful consideration., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

We investigated endogenous tissue response to a woven and electrospun polydioxanone (PDO) and polycaprolactone (PCL) patch intended for tendon repair. A sheep tendon injury model characterised by a natural history of consistent failure of healing was chosen to assess the biological potential of woven and aligned electrospun fibres to induce a reparative response. Patches were implanted into 8 female adult English Mule sheep. Significant infiltration of tendon fibroblasts was observed within the electrospun component of the patch but not within the woven component. The cellular infiltrate into the electrospun fibres was accompanied by an extensive network of new blood vessel formation. Tendon fibroblasts were the most abundant scaffold-populating cell type. CD45 + , CD4 + and CD14 + cells were also present, with few foreign body giant cells. There were no local or systemic signs of excessive inflammation with normal hematology and serology for inflammatory markers three months after scaffold implantation. In conclusion, we demonstrate that an endogenous healing response can be safely induced in tendon by means of biophysical cues using a woven and electrospun patch.

Background: Pathology of the digital flexor tendon sheath is a significant cause of lameness in the horse. Imaging is important to identify lesions and inform on prognosis prior to tenoscopic surgery., Objectives: To use a large population to evaluate 1) the sensitivity and specificity of digital flexor tendon sheath (DFTS) contrast radiographs in diagnosing manica flexoria (MF) tears, deep digital flexor tendon (DDFT) tears and constriction of the palmar/plantar annular ligament (PAL) using novel criteria; 2) predisposition to pathology in signalment and limb affected., Study Design: Multicentre retrospective cohort study., Methods: The medical records of 206 horses with lameness localised to the DFTS, contrast radiographs and subsequent tenoscopic surgery were reviewed. Breed and limb predispositions were evaluated for pathology of the DDFT, MF and PAL constriction. Contrast radiographs of the DFTS were reviewed by four masked operators and for each pathology the sensitivity, specificity and interobserver variability were calculated., Results: Contrast tenography was a sensitive test for MF tears (92% confidence interval [CI] 88.4-94.4%; specificity 56%, CI 51.1-61.1%) and specific for diagnosing DDFT tears (73%, CI 68.6-76.8%; sensitivity 54%, CI 47.8-60.2%) but had a lower sensitivity (71%, CI 65.1-75.9% ) and specificity (45%, CI 39.1-52.0%) for PAL constriction. It had good to substantial interobserver agreement for MF and DDFT tears (Krippendorff's alpha 0.68 and 0.46 respectively). Ponies (57%) and cobs (58%) were significantly more likely to be affected with MF tears (other breeds 20-39%, P = 0.003) and Thoroughbreds (50%), warmbloods (45%) and draught breeds (48%) were more likely to have DDFT tears (other breeds 22-34%, P = 0.01). MF tears and PAL constriction were overrepresented in the hindlimbs compared to DDFT tears in forelimbs., Main Limitations: No standardisation of contrast radiographs was possible. The subjectivity of diagnosis of PAL constriction may also have led to bias. Radiographs were read as JPEGS reducing ability to manipulate images., Conclusions: Contrast radiography of the DFTS is accurate in the pre-operative diagnosis of DFTS pathologies. Different pathologies are overrepresented in certain breeds and limbs., (© 2019 EVJ Ltd.)

Tendon/ligament mineralization is recognized in horses but information regarding its clinical significance is limited. The aims of this observational study were to report the structures most commonly affected by ultrasonographically detectable mineralization and, for these, determine frequency of diagnosis and key clinical features. Cases presented at our hospital in April 1999-April 2013 and September 2014-November 2015 were included: a total of 27 horses (22 retrospective, five prospective). Mineralizations were most common in deep digital flexor tendons (10) and suspensory ligament branches (eight), representing 10% and 7% (estimated), respectively, of horses diagnosed with injuries to these structures during the study. Two deep digital flexor tendon and three suspensory ligament branch cases showed bilateral mineralization. Deep digital flexor tendon mineralization was restricted to the digital flexor tendon sheath, most commonly in the proximal sheath (±sesamoidean canal), and seven of 10 cases involved hindlimbs. Suspensory ligament branch mineralization was visible in the same ultrasound window as the proximal sesamoid bones in 10/11 limbs and six of eight cases involved forelimbs. Previous corticosteroid medication was a feature of one deep digital flexor tendon and one suspensory ligament branch case. Mineralization was associated with lameness in some but not all limbs. Mineralized foci within the deep digital flexor tendon preceded hypoechoic lesion formation in two limbs. Of the cases with deep digital flexor tendon or suspensory ligament branch injury only, one of three and two of three cases, respectively, became sound. Findings indicated that tendon/ligament mineralization can be associated with lameness in some horses, but can also be an incidental finding., (© 2018 American College of Veterinary Radiology.)

Background: Intra-synovial tendon injuries display poor healing, which often results in reduced functionality and pain. A lack of effective therapeutic options has led to experimental approaches to augment natural tendon repair with autologous mesenchymal stem cells (MSCs) although the effects of the intra-synovial environment on the distribution, engraftment and functionality of implanted MSCs is not known. This study utilised a novel sheep model which, although in an anatomically different location, more accurately mimics the mechanical and synovial environment of the human rotator cuff, to determine the effects of intra-synovial implantation of MSCs., Methods: A lesion was made in the lateral border of the lateral branch of the ovine deep digital flexor tendon within the digital sheath and 2 weeks later 5 million autologous bone marrow MSCs were injected under ultrasound guidance into the digital sheath. Tendons were recovered post mortem at 1 day, and 1-2, 4, 12 and 24 weeks after MSC injection. For the 1-day and 1-2-week groups, MSCs labelled with fluorescent-conjugated magnetic iron-oxide nanoparticles (MIONs) were tracked with MRI, histology and flow cytometry. The 4, 12 and 24-week groups were implanted with non-labelled cells and compared with saline-injected controls for healing., Results: The MSCs displayed no reduced viability in vitro to an uptake of 20.0 ± 4.6 pg MIONs per cell, which was detectable by MRI at minimal density of ~ 3 × 10 4 cells. Treated limbs indicated cellular distribution throughout the tendon synovial sheath but restricted to the synovial tissues, with no MSCs detected in the tendon or surgical lesion. The lesion was associated with negligible morbidity with minimal inflammation post surgery. Evaluation of both treated and control lesions showed no evidence of healing of the lesion at 4, 12 and 24 weeks on gross and histological examination., Conclusions: Unlike other laboratory animal models of tendon injury, this novel model mimics the failed tendon healing seen clinically intra-synovially. Importantly, however, implanted stem cells exhibited homing to synovium niches where they survived for at least 14 days. This phenomenon could be utilised in the development of novel physical or biological approaches to enhance localisation of cells in augmenting intra-synovial tendon repair.

Aim: The purpose of this study was to investigate the effect of normal synovial fluid (SF) on exposed endogenous tendon-derived cells (TDCs) and engrafted mesenchymal stem cells (MSCs) within the tendon extracellular matrix., Methods: Explants from equine superficial digital flexor (extra-synovial) and deep digital flexor tendons (DDFTs) from the compressed, intra-synovial and the tensile, extra-synovial regions were cultured in allogeneic or autologous SF-media. Human hamstring explants were cultured in allogeneic SF. Explant viability was assessed by staining. Proliferation of equine monolayer MSCs and TDCs in SF-media and co-culture with DDFT explants was determined by alamarblue®. Non-viable Native Tendon matrices (NNTs) were re-populated with MSCs or TDCs and cultured in SF-media. Immunohistochemical staining of tendon sections for the apoptotic proteins caspase-3, -8, and -9 was performed., Results: Contact with autologous or allogeneic SF resulted in rapid death of resident tenocytes in equine and human tendon. SF did not affect the viability of equine epitenon cells, or of MSCs and TDCs in the monolayer or indirect explant co-culture. MSCs and TDCs, engrafted into NNTs, died when cultured in SF. Caspase-3, -8, and -9 expression was the greatest in SDFT explants exposed to allogeneic SF., Conclusions: The efficacy of cells administered intra-synovially for tendon lesion repair is likely to be limited, since once incorporated into the matrix, cells become vlnerable to the adverse effects of SF. These observations could account for the poor success rate of intra-synovial tendon healing following damage to the epitenon and contact with SF, common with most soft tissue intra-synovial pathologies.