Safety assessment of equine allogeneic tenogenic primed mesenchymal stem cells in horses with naturally occurring tendon and ligament injuries.

Background: Mesenchymal stem cells provide a valuable treatment option in orthopedic injuries in horses. Objectives: The aim of this study was to evaluate the hematological, biochemical, immunological and immunomodulatory parameters following intralesional treatment with tenogenic primed equine allogeneic peripheral blood-derived mesenchymal stem cells (tpMSCs) in client-owned horses with naturally occurring superficial digital flexor tendon (SDFT) and suspensory ligament (SL) injuries. Methods: The immunogenicity and immunomodulatory capacities of tpMSCs were assessed in a modified mixed lymphocyte reaction, including peripheral blood mononuclear cells (PBMCs) of 14 horses with SDFT and SL injuries after treatment with tpMSCs. In a second study, 18 horses with SDFT and SL injuries received either an intralesional injection with tpMSCs (n = 9) or no treatment (n = 9). Results: The tpMSCs did not provoke a cellular immune response (p < 0.001) and were able to immunomodulate stimulated T lymphocytes (p < 0.001) in vitro. Therapeutic use of tpMSCs did not result in relevant hematologic or biochemical abnormalities. Main limitations: Both studies had a small sample size. No statistical analyses were performed in the second study. Fibrinogen was only analyzed in a single horse prior to treatment. Conclusion: Co-incubation of tpMSCs and PBMCs of horses that have been previously exposed to tpMSCs did not elicit a cellular immune response and tpMSCs were able to immunomodulate stimulated T lymphocytes. Intralesional treatment with tpMSCs did not provoke abnormal changes in hematological and biochemical parameters.

Racing performance of Thoroughbred racehorses with suspensory ligament branch desmitis treated with mesenchymal stem cells (2010-2019).

BACKGROUND: Suspensory ligament branch desmitis (SLBD) is a common injury in Thoroughbred racehorses. Orthobiologic treatment of these injuries is a relatively new approach, and there is limited information available on post injury racing performance in racehorses treated with mesenchymal stem cells (MSCs). OBJECTIVES: To assess racing performance post injury in Thoroughbred racehorses with SLBD treated with MSCs. STUDY DESIGN: Retrospective case series. METHODS: Medical records of racehorses with SLBD treated with MSCs from 2010 to 2019 were reviewed. All horses were treated with allogeneic stem cells injected locally at the time of diagnosis and subsequently received 3-4 treatments with autologous bone-marrow derived MSCs. Ultrasonographic and radiographic images were evaluated to determine the degree of suspensory branch injury and sesamoiditis of the associated proximal sesamoid bone. Race performance was assessed by career length, class of races, number of starts and earnings post injury. Race performance of horses that raced pre and post injury were compared. RESULTS: Of 69 treated horses, 71% (49/69) [95% CI: 59%-81%] raced post injury. Horses that had raced pre injury were more likely to race post injury (90% [18/20]) than horses that did not race pre injury (63% [31/49]; p = 0.03). Females were less likely to race post injury than males (52% [11/21] vs. 79% [38/49], respectively; p = 0.02). In the 18 horses that raced pre and post injury, the number of races, earnings and earnings per start were not significantly different pre and post injury. The average career length of all horses that raced post injury was 29.5 months. MAIN LIMITATIONS: Retrospective study design and lack of controls. CONCLUSIONS: Treatment with MSCs resulted in a majority of Thoroughbred racehorses with SLBD racing post treatment. Racing pre injury and being male was positively associated with racing post injury.

Desmitis of the accessory ligament of the deep digital flexor tendon in the forelimb: A retrospective case study of 91 horses.

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.

Equine allogeneic tenogenic primed mesenchymal stem cells: A clinical field study in horses suffering from naturally occurring superficial digital flexor tendon and suspensory ligament injuries.

BACKGROUND: Mesenchymal stem cells are an innovative therapeutic for various equine orthopaedic diseases, including soft tissue injuries. OBJECTIVES: To evaluate the safety and efficacy of tenogenic primed equine allogeneic peripheral blood-derived mesenchymal stem cells (tpMSCs) in horses with naturally occurring superficial digital flexor tendon (SDFT) and suspensory ligament (SL) injuries. STUDY DESIGN: Multicentre, blinded, randomised, placebo-controlled clinical trial. METHODS: One hundred client-owned horses with SDFT and SL injuries were randomised to receive an intralesional tpMSC (66) or saline (34) injection. Clinical and ultrasonographic evaluation was performed before treatment and on Days 56 ± 3 and 112 ± 3 after treatment. Long-term data on re-injury was collected up to 2 years after treatment. RESULTS: Significantly more tpMSC-treated horses achieved improvement in fibre alignment score (FAS) (100% vs. 54.5%, p < 0.001) and echogenicity (97.0% vs. 57.6%, p < 0.001) on Day 112 ± 3, and their lesion size decreased significantly (-27.6 ± 25.91 vs. -4.6 ± 26.64 mm2 , p < 0.001) compared to the placebo group. A FAS = 0 was achieved in 65% of tpMSC-treated horses, as compared to 9% of placebo-treated horses at Day 112 ± 3. The attending veterinarians reported no re-injury in 41 of 53 tpMSC and in 2 of 26 saline-treated horses available for long-term follow-up (p < 0.001). MAIN LIMITATIONS: As this study consisted of client-owned horses, no samples for histology were collected. Long-term follow-up was only available for a subset of enrolled horses. CONCLUSIONS: The intralesional administration of tpMSCs was safe and improved the quality of healing and long-term outcomes in sports horses with naturally occurring SDFT and suspensory injuries.

Equine Autologous Conditioned Serum and Autologous Protein Solution.

Orthobiologics are used with increasing frequency in equine musculoskeletal disease to improve the quality of the repair tissue and prevent reinjury. Autologous blood-based products, or hemoderivatives, are made by processing the patient's blood using different systems to produce a final therapeutic product. Autologous conditioned serum (ACS) and autologous protein solution (APS) are commonly used to treat joint disorders and can also be used treat tendon and ligament injuries. Hemoderivatives contain increased concentrations of anti-inflammatory and immunomodulatory cytokines, and growth factors that help direct tissue healing and repair. The specifics of ACS and APS for treatment of musculoskeletal injuries are discussed.

Genetic architecture and polygenic risk score prediction of degenerative suspensory ligament desmitis (DSLD) in the Peruvian Horse.

Introduction: Spontaneous rupture of tendons and ligaments is common in several species including humans. In horses, degenerative suspensory ligament desmitis (DSLD) is an important acquired idiopathic disease of a major energy-storing tendon-like structure. DSLD risk is increased in several breeds, including the Peruvian Horse. Affected horses have often been used for breeding before the disease is apparent. Breed predisposition suggests a substantial genetic contribution, but heritability and genetic architecture of DSLD have not been determined. Methods: To identify genomic regions associated with DSLD, we recruited a reference population of 183 Peruvian Horses, phenotyped as DSLD cases or controls, and undertook a genome-wide association study (GWAS), a regional window variance analysis using local genomic partitioning, a signatures of selection (SOS) analysis, and polygenic risk score (PRS) prediction of DSLD risk. We also estimated trait heritability from pedigrees. Results: Heritability was estimated in a population of 1,927 Peruvian horses at 0.22 ± 0.08. After establishing a permutation-based threshold for genome-wide significance, 151 DSLD risk single nucleotide polymorphisms (SNPs) were identified by GWAS. Multiple regions of enriched local heritability were identified across the genome, with strong enrichment signals on chromosomes 1, 2, 6, 10, 13, 16, 18, 22, and the X chromosome. With SOS analysis, there were 66 genes with a selection signature in DSLD cases that was not present in the control group that included the TGFB3 gene. Pathways enriched in DSLD cases included proteoglycan metabolism, extracellular matrix homeostasis, and signal transduction pathways that included the hedgehog signaling pathway. The best PRS predictive performance was obtained when we fitted 1% of top SNPs using a Bayesian Ridge Regression model which achieved the highest mean of R2 on both the probit and logit liability scales, indicating a strong predictive performance. Discussion: We conclude that within-breed GWAS of DSLD in the Peruvian Horse has further confirmed that moderate heritability and a polygenic architecture underlies the trait and identified multiple DSLD SNP associations in novel tendinopathy candidate genes influencing disease risk. Pathways enriched with DSLD risk variants include ones that influence glycosaminoglycan metabolism, extracellular matrix homeostasis, signal transduction pathways.

Electrohydraulic Shockwave for Treatment of Forelimb Superficial Digital Flexor Tendinitis and Proximal Suspensory Desmitis in Horses.

Superficial digital flexor tendinitis (SDFT) and proximal suspensory desmitis (PSD) are common causes of lameness in horses. Current treatment options include rest, controlled exercise, administration of anti-inflammatories, intralesional injections, surgery, and electrohydraulic shock wave therapy (ESWT). ESWT is safe, noninvasive, and is used to treat a variety of musculoskeletal abnormalities. Medical records between 2010 and 2021 were reviewed. Horses were separated into two categories: (group 1: ≥ 3 ESWT treatments; group 2: < 3 ESWT treatments). Our objective was to examine the effect of the number of ESWT treatments in the management of SDFT and PSD injuries and to compare short- and long-term outcomes for the two groups. For group 1, lameness scores between the first and third treatments were significantly reduced in both PSD (P < .0001) and SDFT (P = .016) horses. However, neither the PSD (P = .062) nor SDFT's (P = .125) ultrasound findings were significantly different at the end of the third treatment. Horses with PSD showed a significant improvement in forelimb lameness between the first and third treatments compared to hindlimb (P = .033). In the multivariable ordered logistic regression model, only time (months of follow-up) was significantly associated with a positive outcome (P = .001) and there was no difference in short and long-term outcome between groups 1 and 2. Also, chronicity of injury was negatively associated with improvement of lameness (P = .028).

Chronic Collateral Sesamoidean Desmopathy in Draft Horses: Magnetic Resonance Imaging and Histopathological Findings.

Desmopathy of the collateral sesamoidean ligament (CSL) is an unusual disorder in draft horses. This study records the magnetic resonance imaging (MRI) features of chronic CSL desmopathy in eight draft horses and confirms these features by histopathology. The recorded chronic CSL desmopathy has usually affected the forelimbs (100%) and commonly bilateral (62.5%). All horses showed positive proximal digital nerve block, positive front digital flexion test, and negative interphalangeal extension test. Radiography revealed no osseous abnormalities in all feet. MRI features of chronic CSL desmopathy included thickening of the ligament with increased moderate intensity in fast low-angle shot, T1 turbo spin echo, and proton density images in the affected part of the ligament. Chronic CSL desmopathy was concomitant with deep digital flexor tendon injury and distal sesamoidean impar desmitis. In most chronic cases of CSL desmopathy, heterogeneous signal intensities were seen with multiple foci of low signal intensities interlaced with increased moderate signal intensities of thickened CSL. Histopathology confirmed the MRI findings and revealed separated bundles and fascicles by septa of less organized and loose connective tissues containing fibroblasts and loose collagen fibers. Multifocal islands of cartilaginous metaplasia, mineralized areas, and dystrophic calcification were observed in the injured ligament. In conclusion, chronic CSL desmopathy may progress to cartilaginous metaplasia and dystrophic calcification. MRI is a beneficial diagnostic and prognostic tool for chronic CSL desmopathy, and histopathology is a gold standard to document the MRI findings associated with CSL dysmopathy in draft horses.

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis.

BACKGROUND: Equine degenerative suspensory ligament desmitis (DSLD) is a systemic connective tissue disorder first identified in Peruvian Paso horses but afflicting other horse breeds as well. Inappropriate accumulation of proteoglycans in connective tissues, most prominently in tendons and ligaments, leads to progressive and debilitating lameness and pain. It is largely unknown what drives the overproduction of proteoglycans, but our previous studies suggest involvement of bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor-ß (TGFß) family, impacting synthesis of proteoglycans. To identify potential players in pathogenesis of DSLD a new approach utilizing next generation sequencing was undertaken. METHODS: Next generation sequencing was performed using RNA extracted from skin biopsies of six control Peruvian Pasos and six horses with DSLD (4 Peruvian Pasos and 2 warmbloods). The CuffDiff result sets were validated with algorithms used to run them. This was based on the determined false discovery rates derived from the P values adjusted for multiple testing for any given result. RESULTS: Bioinformatics analysis of transcriptomes revealed differential expression of over 1500 genes, including increased expression of genes for several growth factors (most prominently BMP2, FGF5, CTGF, many members of the EGF family), and mediators of signaling (Fos, Myc, MAPK system), and keratins. Two genes encoding for enzymes involved in synthesis of hyaluronan were also overexpressed. Gene expression was decreased for protein cores of many proteoglycans, several growth factors, most collagens, and many peptides with immune function. CONCLUSIONS: The overexpression of BMP2 correlates well with our previous data. However, the decrease in expression of numerous proteoglycans was unexpected. A mutation in a gene of a less characterized proteoglycan and/or glycosyltransferase with subsequent increased production of hyaluronan and/or a proteoglycan(s) undetected in our study could account for the systemic proteoglycan deposition. Decreased collagen gene expression indicates abnormal connective tissue metabolism. The increased expression of keratin genes and FGF5 supports reports of skin abnormalities in DSLD. Underexpression of immune function genes corresponds with lack of inflammation in DSLD tissues. Finally, though the proteoglycan and/or glycosaminoglycan abundant in DSLD has not been identified, we validated our previous data, including overexpression of BMP2, and systemic nature of DSLD due to disturbed metabolism of the extracellular matrix.

Standing low-field MRI of the equine proximal metacarpal/metatarsal region is considered useful for diagnosing primary bone pathology and makes a positive contribution to case management: A prospective survey study.

High-field MRI of the proximal metacarpal/metatarsal region has been associated with great diagnostic potential and clinical reports of standing low-field MRI of the forelimb suggest the same. To better understand diagnostic outcomes with standing low-field MRI of the proximal suspensory region, a prospective survey study was conducted and users of a widely available system questioned on their experience, operating procedures, and interpretation of standing low-field MRI findings. Response data included scores on a modified Likert scale from which weighted ratings were calculated for statistical analyses. Depending on the question, responses were obtained from 17 to 29 of the 38 invited facilities. Users indicated that standing low-field MRI was most frequently performed in the face of equivocal diagnostic findings; compared to Sports horses, general purpose riding horses were thought less likely to have detectable abnormalities and standing low-field MRI was rated most useful for the detection of primary bone pathology in the proximal metacarpal region. Standing low-field MRI signal change involving both the suspensory ligament and adjacent bone concurrently was rated most relevant and abnormalities solely affecting the muscle/adipose tissue bundles least relevant for diagnosing suspensory ligament injury. Transverse scans and in decreasing order T1-weighted gradient echo, short-tau inversion recovery FSE, T2*-weighted gradient echo, and T2-weighted FSE sequences were most frequently acquired and judged most useful by the majority of users experienced in imaging of the target area. This survey supports the relevant impact of standing low-field MRI on clinical case management, particularly in the context of imaging the proximal metacarpal region.

Histological and immunohistochemical evaluation of two cell therapy protocols in equine suspensory ligament repair / Avaliação histológica e imunoistoquímica do reparo do ligamento suspensório equino tratado com dois protocolos de terapia celular

This study aimed to histologically evaluate the quality of tissue repair in equine suspensory ligament treated with two cell therapy protocols. All four limbs of six animals were operated simultaneously to remove a fragment in each ligament using a skin biopsy punch. Two days later, intralesional injections were performed using bone marrow mononuclear fraction (BM group), cultivated cells derived from adipose tissue (AT group), saline (positive control group), or no treatment (negative control group), in such way that each horse received all treatments. After sixty days biopsies were performed for histological analysis (H & E, Masson's trichrome and picrosirius red) and immunohistochemistry analysis (collagen type III). Histological findings (H & E and Masson's trichrome), birefringence intensity (through picrosirius) and collagen type III expression (through immunohistochemistry) were analyzed. Samples from treated groups had better birefringence intensity (P=0.007) and fiber alignment scores were superior compared to controls, though not statistically significant (P=0.08). Presence of inflammatory cells and intense staining for collagen type III occurred in all groups demonstrating an active healing process. In conclusion, both protocols resulted in improvement of tissue repair indicating their potential to be used as an adjuvant treatment of equine suspensory ligament disorders.(AU)

Este estudo teve como objetivo a avaliação histológica e imunoistoquímica do reparo do ligamento suspensório equino tratado com dois protocolos de terapia celular. Os quatro membros dos seis animais do experimento foram submetidos a procedimento cirúrgico em que um fragmento de cada ligamento foi retirado, utilizando-se punch de biópsia. Dois dias após o procedimento, aplicações intralesionais foram realizadas, por meio de aspirado de medula óssea (bone marrow-BM), células mesenquimais derivadas de tecido adiposo (adipose tissue-AT), solução salina (positive control group-PC) ou controle (negative control-NC). Após 60 dias, biópsias foram retiradas da região de reparo dos ligamentos e foram submetidas à análise histológica (HE, tricrômio de Masson, picrosírius red) e imunoistoquímica (colágeno tipo III). Diferentes variáveis histológicas (HE e tricrômio de Masson), a intensidade de birrefringência das fibras colágenas (picrosírius red) e a expressão de colágeno tipo III foram avaliadas. Os grupos tratados apresentaram maior birrefringência (P=0,007) e alinhamento de fibras (P=0,08) comparados ao controle, para o qual o resultado não se mostrou estatisticamente significativo. Achados histológicos e imunoistoquímicos demonstraram um processo ativo de reparo tecidual em todos os grupos. Concluiu-se que os dois protocolos de terapia celular apresentaram melhora no reparo tecidual, demonstrando potencial terapêutico adjuvante no tratamento de afecções do ligamento suspensório equino.(AU)

Prospective randomized comparison of platelet rich plasma to extracorporeal shockwave therapy for treatment of proximal suspensory pain in western performance horses.

Proximal suspensory desmitis (PSD) is a frequent cause of lameness in the performance horse. Extracorporeal shockwave therapy (EST) and platelet rich plasma (PRP) have become common treatments for PSD yet clinical data on efficacy is limited. The main objective of this randomized, prospective clinical study was to compare long-term effectiveness of EST and PRP in Western performance horses. One hundred horses with lameness localized to the proximal suspensory ligament received treatment with either PRP or EST following baseline ultrasonographic evaluation. A veterinarian and agent evaluated the horses for lameness independently four days following the first treatment and long-term follow up was obtained from the agent at six and twelve months. Four days post treatment, horses treated with EST had significantly greater lameness improvement compared to PRP. At one-year horses with less severe baseline ultrasound changes (grades 0-1) appeared to respond better (degree of lameness) with EST treatment whereas horses with more severe ultrasound changes (grade 2) responded better to PRP. Horses with baseline lameness graded 1 or 2 were 5.1 times more likely to be back in work at 1 year compared to those presenting with grade 3 or 4. EST treatment was associated with going back to work 3.8 times more at one year compared to PRP independent of baseline ultrasound score. Both PRP and EST can be expected to yield favorable therapeutic responses in Western performance horses with lameness localized to the proximal suspensory region. Baseline ultrasound may guide treatment selection.

Ultrasonic debridement with stem cell therapy of suspensory branch desmitis in an equine patient.

Ultrasonic debridement as a treatment for tendinopathy and desmitis is a relatively new approach in orthopedic surgery. Previously only used in limited cases, this procedure shows promise for treating ligament-bone and tendon-bone interface injuries. We present a case study of a 2-yr-old thoroughbred male horse, unable to train due to recalcitrant symptoms after extensive conservative management of suspensory branch desmitis. It was then treated with ultrasonic debridement and concurrent manubrial stem cell autograft injection, to treat the ultrasound visualized lesion. Post-surgically, the patient recovered quickly, began training within 16 wk, and went onto win several races. Repeat ultrasound imaging reveals a complete restoration of the internal fiber architecture of the ligament. With a 3-yr follow-up, there has been consistent training and race performance with no re-injury. This study is the first to document the successful outcome of ultrasonic debridement with concurrent stem cell injection in the treatment of equine desmitis.

Intermediate patellar ligament desmopathy often occurs in conjunction with other stifle abnormalities.

Intermediate patellar ligament (IPL) desmopathy is a relatively uncommon injury previously reported to have a poor prognosis for return to athletic activity. There is little documentation of the clinical and ultrasonographic features, clinical significance, and outcome for return to work following IPL injury in horses. The aim of this retrospective descriptive study was to describe the clinical and ultrasonographic features of IPL desmopathy, its association with other injuries of the stifle, and outcome for return to work following injury. Forty-two stifles with an ultrasound diagnosis of IPL desmopathy over a 5-year time period were included. Data regarding signalment, clinical presentation, diagnostic imaging findings, treatment, and outcome are described. Intermediate patellar ligament desmopathy occurred most commonly in the midbody (35/42; 83%) of the ligament and lesions were predominantly hypoechoic discrete tears (31/42; 74%) that were obliquely oriented in a craniolateral to caudomedial direction (28/42; 67%). Rarely (1/42; 2%) was IPL desmopathy the only ultrasonographic abnormality detected. Of 13 horses that underwent recheck ultrasound examination, the majority (11/42; 85%) either did not improve or worsened ultrasonographically. Despite this, of 25 horses with long-term follow-up, 23 (92%) returned to work, 16 at the same level or higher. A variety of treatments were utilized. The clinical significance of IPL desmopathy is difficult to determine because it is usually found in conjunction with other stifle abnormalities. Although IPL desmopathy rarely shows ultrasonographic improvement over time, prognosis can be good for return to work.

Does BMP2 play a role in the pathogenesis of equine degenerative suspensory ligament desmitis?

OBJECTIVE: Horses afflicted with degenerative suspensory ligament desmitis (DSLD) suffer from progressive leg pain and lameness without history of trauma. DSLD is a systemic disorder caused by abnormal accumulation of proteoglycans in many connective tissues. One proteoglycan found in higher quantities in DSLD is decorin. The accumulated decorin has an abnormally glycosylated glycosaminoglycan chain in DSLD. In addition to acellular accumulations of proteoglycans foci of active fibroblasts/tenoblasts were observed in some tendons and suspensory ligaments (SLs) from DSLD cases We have hypothesized that this represents an early event in DSLD and that production of chondrogenic growth factors, such as BMP2, and/or enzyme participating in glycosylation of glycosaminoglycans is a major factor in initiation and progression of DSLD. RESULTS: Using immunohistochemistry we have identified BMP2 in these cellular foci, indicating association with proteoglycan production, but not in other cells in the tendon and SLs. In contrast, very little staining for TGFß and dermatan sulfate epimerase, an enzyme involved in glycosylation of glycosaminoglycan chains, was observed in these foci and other cells in both control and DSLD-affected tendons and SLs. Our data support our hypothesis that chondrogenic growth factors may be responsible, at least in part for progression of DSLD in horses.

Regenerative Medicine and Rehabilitation for Tendinous and Ligamentous Injuries in Sport Horses.

Tendon and ligament injuries are a common source of lameness in the athletic horse. Although tendons and ligaments have the ability to spontaneously heal, lesions tend to fill with biomechanically inferior fibrous tissue such that the horse is prone to reinjury. Regenerative medicine is used to improve quality of repair tissue and prevent reinjury. Platelet-rich plasma, stem cells, and autologous conditioned serum are the most commonly used orthobiologics in the horse. A tailored rehabilitation program is key to returning horses to athleticism following injury. The specifics of regenerative medicine and rehabilitation for tendonitis and desmitis in the horse are discussed.

Histological changes in the proximal suspensory ligament after neurectomy of the deep branch of the lateral palmar nerve of horses with induced proximal suspensory desmitis.

Proximal suspensory desmitis (PSD) is a common cause of lameness in the pelvic limb, but could also affect the thoracic limb of competing and non-competing horses. Most horses diagnosed with PSD in a thoracic limb respond to rest followed by controlled exercise, but in a small percentage of affected horses, lameness persists. In one study, four horses chronically lame because of PSD in a thoracic limb became sound after neurectomy of the deep branch of the lateral palmar nerve (DBLPaN), which innervates the proximal aspect of the suspensory ligament (SL; Guasco et al., 2013). Whether neurectomy of the DBLPaN results in changes in the SL that might predispose the horse to re-injury is not known. The aim of this study was to describe the findings observed during quantitative lameness evaluation, gross and histological examination of the proximal portion of the suspensory ligament (SL) of the thoracic limbs of eight horses after neurectomy of the DBLPaN performed after inducing unilateral PSD by injecting collagenase into the proximal portion of the SL. The clinical response to neurectomy was resolution of lameness in all horses. Muscle fibers of the denervated ligaments presented atrophy and were infiltrated with fat and connective tissue, thereby reducing the strength and elasticity of the ligament.

Equine Dental Pulp Connective Tissue Particles Reduced Lameness in Horses in a Controlled Clinical Trial.

OBJECTIVE: To assess if injection of allogeneic dental pulp tissue particles would improve lameness in horses with naturally occurring osteoarthritis (OA) or soft tissue (ST) injury. DESIGN: Prospective, randomized, blinded, and controlled clinical trial and client survey assessment. ANIMALS: Forty lame client-owned horses. PROCEDURES: Sterile dental pulp, recovered from otherwise healthy foals that perish during dystocia, was processed under good manufacturing processing to produce mechanically manipulated, unexpanded pulp tissue particles containing viable cells surrounded in extracellular matrix. Forty lame client-owned horses with confirmed OA (n = 20), or ST injury (desmitis or tendonitis) received a 2 mL intra-articular (n = 20 OA) or intra-lesional (n = 20) injection of control transport vehicle (n = 20) or 10 × 106 dental pulp tissue particles (n = 20). Acclimatized horses had baseline measurements performed and were then injected on day 0. Horses were treadmill exercised for 2 weeks, evaluated by clinical parameters, lameness score, edema (score and circumference), pain on flexion (OA) or pressure (ST), and clients' scores for pain and discomfort before and through 45 days after pulp injection. Twenty horses were available for >2.5-year follow-up. RESULTS: Pulp-treated horses showed decrease in lameness compared to baseline (P < 0.009) or placebo controls (P < 0.013) for at least 2 weeks. Client assessments of comfort were improved between before and 45 days after pulp injection (P < 0.001). Clinical improvement with ST injury was significantly greater than OA (P < 0.001). At >2.5-year follow-up, at least 10 horses were in work. CONCLUSION AND CLINICAL RELEVANCE: Dental pulp tissue particles can be considered as a treatment option for equine lameness due to OA, desmitis, or tendonitis.

Magnetic Resonance Imaging-Guided Treatment of Equine Distal Interphalangeal Joint Collateral Ligaments: 2009-2014.

OBJECTIVES: To determine the outcome of treating distal interphalangeal joint collateral ligament (DIJCL) desmopathy using magnetic resonance imaging (MRI)-guided ligament injection. METHODS: Medical records of 13 adult horses diagnosed with DIJCL desmopathy using low-field MRI and treated by MRI-guided ligament injection of mesenchymal stem cells and/or platelet-rich plasma (PRP) were reviewed. Information collected included signalment, MRI diagnosis, treatment type, time to resolution of lameness, and level of exercise after treatment. RESULTS: Collateral ligament inflammation was diagnosed as a cause of lameness in 13 horses. MRI was used to guide the injection of the injured DIJCL. All lameness attributed to DIJCL desmopathy resolved with the resulting level of performance at expected (10) or less than expected (3). CONCLUSION AND CLINICAL RELEVANCE: Injection of the DIJCL can be safely completed in horses standing in a low-field magnet guided by MRI as previously demonstrated in cadaver specimens. The positive response in all horses suggests that administration of stem cells or PRP along with rest and appropriate shoeing may be a safe and useful treatment for DIJCL desmopathy.

DYNAMIC SONOGRAPHY OF THE EQUINE METACARPO(TARSO)PHALANGEAL DIGITAL FLEXOR TENDON SHEATH.

Palmar/plantar annular desmitis is a common disease that may be associated with adhesions and structures affecting the flexor tendons, which requires tenoscopy to diagnose. The purpose of this descriptive study was to develop a dynamic sonographic technique for evaluating the motion of normal equine flexor tendons in relation to the palmar/plantar annular ligament and to compare findings with horses previously diagnosed with palmar/plantar annular desmitis. Ten healthy adult horses were examined prospectively and the images of four horses diagnosed with palmar/plantar annular desmitis were retrospectively evaluated. Dynamic sonography was performed at the level of the metacarpo/metatarsophalangeal joint by maximally extending and flexing the interphalangeal joints. Palmar/plantar annular ligament thickness (mm), size of any gap between the flexor tendons, and subjectively increased angulation of the long linear echoes of the superficial digital flexor tendon were measured. The presence of gliding motion between the palmar/plantar annular ligament and superficial digital flexor tendon was determined by consensus. Twenty-eight healthy control limbs (16 hind/12 fore) and four with palmar/plantar annular desmitis (3 hind/1 fore) were evaluated. Controls had unrestricted gliding motion between the palmar/plantar annular ligament and flexor tendons and zero to 13° of angulation of the long linear echoes. The four affected horses had restricted gliding motion and between 20-35° angulation of the long linear echoes. Dynamic ultrasound is a feasible technique for detecting restricted flexor tendon and palmar/plantar annular ligament gliding motion, as well as subjectively increased angulation of the long linear echoes of the flexor tendon in affected horses compared with controls and warrants further investigation.