Tissue in horses refers to the various types of biological material that make up the body of the animal, including muscle, connective, epithelial, and nervous tissues. Each type of tissue has specific functions and characteristics, contributing to the overall physiology and health of the horse. Muscle tissue is responsible for movement and locomotion, connective tissue provides structural support and protection, epithelial tissue covers body surfaces and lines cavities, and nervous tissue is involved in transmitting signals for communication and coordination within the body. The study of equine tissue encompasses aspects such as growth, repair, and response to injury or disease. This page compiles peer-reviewed research studies and scholarly articles that explore the structure, function, and pathology of different tissue types in horses, offering insights into their role in equine health and disease management.
Sfraga H, Demeter EA, Pinn-Woodcock T, Guarino C, Young R, Cronk B, Cercone M.To investigate the presence of subclinical cranial nuchal bursitis and characterize its histopathologic features and association with Borrelia burgdorferi. Unassigned: This was a prospective descriptive cadaver study on a convenience population of horses in a B burgdorferi-endemic region (15 horses: 5 geldings and 10 mares of various breeds; 4 to 29 years old). Horses without history or clinical signs of cranial nuchal bursitis underwent euthanasia and tissue donation. Cranial nuchal bursa, synovial fluid, and nuchal ligament were collected postmortem. The bursa and ligament were evaluated via...
Normélia P Morais A, Gastal GDA, Aguiar FLN, Hyde KA, Gastal MO, Lima LF, Ñaupas LVS, Flávia B Silva A, Becerra VAB, Gheno L, Curcio BR....Understanding how to effectively isolate a large number of healthy follicles is essential for increasing success rates in ARTs, such as in vitro culture and cryopreservation. Late secondary (preantral) and early tertiary (antral) follicles isolated from the intermediary portion of equine ovarian tissue sliced at two different thicknesses (0.25 mm vs. 0.50 mm) were characterized according to regional distribution (dorsal, medial, and ventral), morphofunctional features, and epigenetic profiles. After isolation via microdissection, follicles were evaluated for membrane integrity (trypan blue), v...
Hmb O, L W, M V, Jm W, Ct F.A systematic study of regional skin thickness in different types of horses has not yet been described. Knowledge about regional skin thickness has long been used in human medicine to optimise wound care and skin grafting outcomes and similar knowledge could prove useful in equine wound management. The objective of the current study was to report the topographical variation in skin thickness of Warmblood (WB) and Coldblood (CB) type horses and to compare different methods for measuring skin thickness. Horses free of skin conditions and euthanised for reasons unrelated to this study were include...
Rosa MCB, Campos MEST, Albuquerque AS, Braz MS, Mapele RO, de Oliveira MCG, Toma HS, Ferraz PFP, Pereira RN, Raymundo DL.Skin wounds in horses, particularly in the distal extremities, often heal slowly due to mechanical stress, compromised perfusion, and excessive fibroplasia. This study evaluated the effects of topical Croton lechleri (CL) cream, alone or in combination with nitroglycerin, on the healing of skin wounds in the metatarsal region of horses. Six mares received six standardized wounds in each region and were treated with: saline solution, nitroglycerin (0.1 or 1 mg/mL), CL (1 or 10 µg/mL), or CL + nitroglycerin (10 µg/mL + 1 mg/mL). Wound contraction, histology, and bacterial culture were evaluate...
Li X, Qian S, Yang L, Yang X, Chang X, Zeng Y, Meng J.This study aimed to investigate the relationship between genes and metabolites involved in glycogen metabolism across different tissues of Yili mares using joint transcriptomic and metabolomic analyses. Glycogen content was measured in various tissues (pincer, trapezius, latissimus dorsi, gluteus medius, semitendinosus, external abdominal obliques, liver, and heart) from seven Yili mares. The liver, as the visceral tissue with the highest glycogen content, and the gluteus medius, as the muscle with the highest glycogen content, were selected for transcriptomic sequencing and metabolomic analys...
Amaral A, Cerveira-Pinto M, Santos C, Kordowitzki P, Skarzynski D, Ferreira-Dias G, Szóstek-Mioduchowska A.Transforming growth factor (TGF)-β1 is a pro-fibrotic cytokine that affects extracellular matrix (ECM) deposition and fibroblast activity. 17β-Estradiol (E), the dominant ovarian steroid during the follicular phase (FLP) of the estrous cycle, can also influence ECM remodeling and fibrosis, through prostaglandin (PG) synthesis. PGs have opposing roles in fibrosis, with PGE₂ showing anti-fibrotic effects and PGF₂α promoting fibrosis. Equine endometrosis, whose main pathological feature is fibrosis, is marked by chronic inflammation and ECM accumulation, and may involve mediators like TGF-...
Keller LE, Kelly TN, Chevalier JM, Jung HJ, Pearson GB, Begum L, Beane OS, Bhumiratana S, Fortier LA.Fresh osteochondral allograft (OCA) transplantation effectively repairs cartilage and subchondral bone; however, the persisting shortage of available donor OCAs and their short shelf-life make scheduling surgeries and meeting patient demand challenging. Attempts have been made to develop tissue-engineered solutions to address the limitations of OCA; nonetheless, these have failed to progress beyond the preclinical stage. Objective: To assess the safety and efficacy of a tissue-engineered osteochondral allograft (TE-OCA) as compared with equine OCA in an equine osteochondral defect model. Metho...
Bartenschlager F, Kuropka B, Schmitz P, Dumke F, Landmann K, Gruber AD, Weise C, Schnabel CL, Gehlen H, Mundhenk L.Mucus hypersecretion and accumulation are hallmark features of equine asthma (EA), a meaningful respiratory disorder in horses occurring in mild to moderate (MEA) and severe (SEA) forms. Changes of the proteomic composition of airway mucus in EA are poorly understood. Using label-free quantitative liquid chromatography-mass spectrometry, we analyzed airway mucus from SEA (n = 10), MEA (n = 6), and healthy (n = 8) horses. We identified and quantified 2,275 proteins including gel-forming mucins MUC5AC and MUC5B and membrane-bound mucins MUC1 and MUC4. Compared with healthy controls, ...
Verstraete MH, Norris JK, Loux SC, De Spiegelaere W, Carossino M, Daels P, Dini P.The placenta mediates critical interactions between mother and offspring that guide development and impact long-term health. Despite its importance, the cellular organization of the equine (Equus caballus) placenta remains poorly defined. The equine epitheliochorial placenta, characterized by the absence of trophoblast invasion and prominent endocrine activity, provides a unique comparative model for studying placental cellular composition and development. Methods: We applied single-cell RNA sequencing to chorioallantois tissue collected from first-trimester (n = 1) and term (n = 2) equine...
Rissi DR, Mendes RE.Squamous cell carcinoma (SCC) is the most common ocular and periocular neoplasm of horses, typically arising from the limbus, third eyelid mucosa or mucocutaneous junctions of the upper and lower eyelids. Tumours are locally invasive, prone to recurrence and may rarely metastasize. Histological evaluation is required for definitive diagnosis and atypical SCC subtypes may be diagnostically challenging. Here we describe a clear cell SCC in the third eyelid of a 16-year-old female Quarter Horse. The red and invasive mass was surgically excised for histological evaluation. The lesion consisted of ...
Bosman LM, Logan MG, Miszewski A, Pepper MS.Translational regenerative medicine, integrating human and veterinary approaches within the "One Health" framework, increasingly uses horses as models for human musculoskeletal conditions due to shared anatomical and functional features. Osteoarthritis and tendon disorders affect both species, often resulting from high-impact or repetitive strain activities. Regenerative medicine offers therapeutic opportunities by promoting tissue repair and modulating inflammation. Cellular orthobiologics such as mesenchymal stromal/stem cells (MSCs) show promise for treating osteoarthritis and tendon injuri...
Palomino Lago E, Roberts SJ, Orriss IR, Lumsden ES, Guest DJ.Bone is a dynamic tissue that is maintained through the co-ordination of bone resorption and bone formation. An imbalance of these processes can lead to bone disease. In vitro studies of osteoblasts can help to understand bone formation, but primary cells have a limited lifespan in culture. Herein, we report the successful generation of equine immortalized osteoblasts through the stable overexpression of human telomerase reverse transcriptase (hTERT) and Simian virus 40 (SV40) large T-antigen in osteoblasts isolated from trabecular bone taken from the third metacarpal of a two-year-old Thoroug...
Heilen LB, Roßgardt J, Dern-Wieloch J, Vogelsberg J, Staszyk C.Horses' hypsodont (high-crowned) teeth face permanent dental wear. This is compensated for by a continuous eruption, which requires a high adaptability of odontoblasts; otherwise, the dental pulp would be exposed. Here, we report on how equine odontoblasts respond to the challenge of maintaining a high production rate of dentin. We analyzed CD90, a marker of odontoblastic differentiation, and nestin, a marker of mature odontoblasts, in equine pulpal tissue via immunofluorescence. For comparison, we examined the hypselodont (ever-growing) incisors and brachydont (short-crowned) molars of rats. ...
An T, Dugarjaviin M.(1) Background: The dun coat color, a wild-type phenotype in horses characterized by pigment dilution and primitive markings, is regulated by . This study explored the expression and localization of in the Bider marking (a primitive mark unique to the shoulder of horses); (2) Methods: We compared skin tissues from Bider-marked and non-Bider dun Mongolian horses. Samples were collected from the Bider area (dark-colored/light-colored shoulder), dorsal midline, and croup. Histological staining, qRT-PCR, and Western blotting were used to analyze pigment distribution and expression at mRNA and pr...
Richardson LM, Gordon J, Davila C, Chamoun-Emanuelli AM, Zdyrski C, Whitfield-Cargile CM.Gastrointestinal (GI) disease is a major cause of morbidity and mortality in horses, with disruption of the intestinal epithelial barrier playing a central role in disease pathogenesis. A deeper understanding of the molecular and functional properties of the equine intestinal barrier is essential to improve diagnostics and therapeutics. While intestinal organoids have emerged as a promising tool for modeling GI physiology and disease, equine-specific data remain limited. Existing studies vary in methodology and often lack functional characterization, particularly across different intestinal re...
Ver Goltz L, Gomes SP, Schimming BC, Abdala FCM, Miglino MA, de Castro Sasahara TH.The equine ovary exhibits unique structural and developmental features that distinguish it from those of other domestic species, including the presence of an ovulation fossa and an inversion of cortical and medullary layers. This study aimed to investigate the morphostructural development of the equine fetal ovary, with particular emphasis on the formation of the ovulation fossa. Fourteen female equine fetuses, ranging from 70 to 200 days of gestation, were collected from a commercial abattoir. Results revealed a progressive increase in ovarian volume and marked histological changes througho...
Journal of biomechanicsJanuary 16, 2026
Volume 197 113169 doi: 10.1016/j.jbiomech.2026.113169
Collins AE, Wayne JS, Ferrando CA, De Vita R.This experimental study characterizes the elastic behavior of male and female equine genital tissues using uniaxial tensile testing, with strain measurements obtained via digital image correlation. Dog-bone-shaped tissue specimens were excised from mares and geldings (n=23 from female specimens and n=42 from male specimens) with all specimens aligned along the circumferential direction (CD) of the vagina, penis, and scrotum. The results include load-displacement data, stress-strain data, and tangent moduli for the penile sheath, vaginal canal, and scrotum, with strain measured in both the CD a...
Shahid MA, Guitart AS, Bertin FR, Simon O, Ceusters J, Serteyn D, Whitworth DJ.A minimally invasive microbiopsy-based method for the isolation of mesenchymal stem cells (MSCs) from equine skeletal muscle (M-MSCs) provides a readily accessible source of MSCs for clinical applications. We examined the expression of genes associated with immunomodulation and anti-inflammatory pathways, in addition to those of growth factors and the major histocompatibility complex (MHC) molecules I and II, at constitutive levels and after priming with inflammatory cytokines, an immunostimulant, and heat-shocking. While there was notable variation between the M-MSCs from each of the horses i...
Rodrigues MF, Neves AP, Ferreira R, Pessoa GA, Araujo DN, de Souza GV.Melatonin has demonstrated beneficial effects in regulating inflammatory processes in various tissues, but its role in mare uterine physiology remains unclear. Objective: To investigate the effects of melatonin on the gene expression of cytokines (IL-1β, IL-6, IL-8, IL-10, and TNF-α) in equine uterine explants cultured for 6, 12, or 24 hours. Methods: The study was divided into two experiments. Part 1 aimed to evaluate the cytotoxicity of melatonin at concentrations of 0, 0.5, 1, 2, 4, and 8 mM on endometrial cells. Part 2 aimed to determine the expression of inflammatory cytokines in uterin...
Liu X, Liu A, Khan MZ, Zhu Q, Zheng Y, Chen W, Cai B, Yan Z, Peng Y, Wang C.The gene family plays an indispensable role in regulating embryonic development, cell differentiation, and morphogenesis. This study employed bioinformatics approaches for systematic analysis, ultimately identifying 33 gene family members from the donkey genome. Physicochemical property analysis revealed that the number of amino acids encoded ranged from 94 to 444, with 31 members classified as alkaline proteins. Their secondary structure was predominantly composed of random coils and alpha helices, and all members were localized to the nucleus. Conserved motif analysis further demonstrated ...
Arevalo-Turrubiarte M, Edling CE, Moller-Levet C, Forbes B, Kemp V, Weir J, Marr C, Lewis R, Jeevaratnam K.The initiation and maintenance of atrial fibrillation have been associated with physiological alterations in myocardial sleeves of the pulmonary veins (PVs). Gene expression profiles of the myocardial sleeves of the PVs in healthy (n = 3) and paroxysmal atrial fibrillation (PAF) (n = 6) thoroughbred horses (Equus caballus) were studied. Tissue collected from the left superior PV, adjacent to the left atrium, was analyzed by RNA sequencing. Gene Set Enrichment Analysis demonstrated positive enrichment of gene ontology biological processes related to muscle and endothelial cell development, cell...
Underberg BA, Van der Vekens E, Drews B, Kaessmeyer S.Equine laminitis is a complex and potentially fatal disease characterized by severe vascular and inflammatory alterations within the equine foot. This study aimed to develop immunohistochemistry (IHC) protocols for the detection of cyclooxygenase-2 (COX-2) and von Willebrand factor (vWF) in equine feet with and without laminitis, post-mortem perfused with paraffin oil. Unassigned: A total of 12 equine forelimbs from 8 horses were utilized in this study, divided into two study cohorts: one with laminitis and the other as a non-laminitis control. To develop the IHC protocols thoroughly, the tiss...
Meeremans M, Devriendt B, Bairiot S, Van Poucke M, Peelman L, Demeyere K, Meyer E, Van Vlierberghe S, De Schauwer C.Macrophages play key roles in tissue homeostasis and regeneration-associated inflammation. Unlike humans, a reliable protocol to obtain and polarise equine monocyte-derived macrophages is lacking. In this study the polarisation of equine macrophages, derived from CD172a peripheral blood monocytes is described. After differentiation, IFN-γ/LPS or IL-4 were used to induce pro- and anti-inflammatory phenotypes, respectively. Evaluation criteria included morphology, mRNA (RT-qPCR) and protein expression (flow cytometry, immunofluorescence), nitric oxide and arginase production, cytokine secretion...
James AL, Vettorato E, Moura RA, Azevedo TMBPR, Mallicote MF, Chiavaccini L.Sedation with α₂-agonists can impair microcirculation and oxygen delivery. This prospective randomized crossover study investigated whether administering acepromazine maleate before detomidine hydrochloride maintains higher peripheral tissue oxygen saturation (StO₂) in sedated horses. Eight healthy adult horses randomly received intravenous detomidine (10 μg/kg) either alone (D) or in combination with acepromazine (20 μg/kg; DA), with a one-week washout. Hemoglobin concentration and central venous oxygen saturation (ScvO₂) were measured at baseline. Tissue oxygen saturation, tissue ...
Graide H, Duysens J, Frank T, Mouithys-Mickalad A, Niesten A, Sandersen C, Ceusters J, Serteyn D.Musculoskeletal pathologies present challenges in athletic horses, often leading to functional impairment. The slow or limited regenerative capacity of bone, joint, and tendon/ligament injuries, coupled with the limitations of conventional treatments, highlights the need for innovative therapies such as ortho-biologics and mesenchymal stem/stroma cells. Traditional 2D cell culture systems with fetal bovine serum (FBS) fail to replicate the complexity of the in vivo environment, whereas 3D cultures more accurately mimic native tissue architecture and cell-cell interactions. This study describes...
Profaska M, Zarzycka M, Dubniewicz K, Witkowski M, Wieczorek J, Gil D, Wafula S, Lanh DK, Kotula-Balak M.Mare endometrosis remains a poorly understood pathological process. Objective: Mare endometrial tissue with endometrosis was used to determine the effects of relaxin (RLX). Healthy tissues that were left untreated (H), or treated with vehicle (Hveh), and tissues with endometrosis that were left untreated (E), treated with vehicle (Eveh), and treated with RLX (10, 25, 50 nM; ER) were used for an ex vivo system for 72 h. Methods: Tissue histological examination, and immunoenzymatic measurement of the concentrations of transforming growth factor β (TGF-β), interleukins (IL-6 and IL-8), and pr...
Sabzpoosh M, Hoveizi E, Gooraninejad S.This study aimed to extract and isolate endometrial stromal cells from Arabian mares and investigate their growth and differentiation potential. Endometrial biopsies were obtained from three healthy 6-year-old Arabian mares using a standardized, minimally invasive protocol. The isolated cells were characterized using flow cytometry and differentiation analysis. Flow cytometry revealed mesenchymal markers CD90 (95.2%) and CD105 (97.4%) and hematopoietic markers CD34 (1.17%) and CD45 (0.339%). The cells exhibited differentiation potential into adipocytes, osteoblasts, and chondrocytes. The findi...
Da Silva-Álvarez E, Martín-Cano FE, Alonso JM, Becerro-Rey L, Zabalo-Palomo C, Gil MC, Peña FJ, Ortega-Ferrusola C.This study aims to characterize and compare the uterine fluid proteome and cytokine profile of reproductively healthy mares (HM; n = 15) and mares with Streptococcus equi subsp. zooepidemicus (S. zooepidemicus)-associated endometritis (SAE; n = 9). Uterine flush samples collected during the follicular phase were analyzed by shotgun proteomics and multiplex cytokine assays. Equine proteins were mapped to human orthologs, and enrichment and network analyses were performed using g:Profiler, Metascape, ToppGene, and STRING/MCODE. SAE mares showed higher levels of IL-1α, IL-1β, GRO, IL12p...
Partusch L, Rutland CS, Martens A, Du Cheyne C, De Spiegelaere W, Michler JK.Exuberant granulation tissue (EGT) is a second intention wound healing disorder. It commonly occurs in the distal limb of horses. EGT causes significant increase in the duration and cost of treatment, potentially leading to the decision not to pursue treatment and euthanize the patient. The underlying pathomechanisms of this fibroproliferative disorder remain unclear, particularly in terms of collagen composition and the association between myofibroblasts and blood vessels. This study investigated the collagen composition in naturally occurring EGT following trimming in 19 horses (EGT group). ...
Parker JL, Berghaus LJ, Gordon J, Mathews L, Akinde MA, Hall DB, Peroni JF.Mesenchymal stromal cells (MSCs) support wound healing through immunomodulation and by promoting tissue organization. Cell tracking studies demonstrate that MSCs must 'home' to injuries in order to participate in reparative processes. It has been reported that in vivo cell tracking labels, including superparamagnetic iron oxide particles (SPIOs), can alter MSC homing. Homing is thought to occur in coordinated steps including tethering, activation, arrest, diapedesis, and migration, guided by chemotactic stimuli. Equine distal limb injuries, which are commonly treated with MSCs, possess a disti...
Balazs EA, Denlinger JL.Viscosupplementation is a new medical concept that has as its therapeutic goal the restoration of rheological homeostasis in pathological structures such as osteoarthritic joints. When the normal viscoelasticity of a solid tissue compartment or the elastoviscosity of a liquid tissue compartment is decreased under pathological conditions, normal function and regenerative processes are impaired. By introducing viscosupplementary devices, the normal rheological state of such compartments is restored or augmented. These devices stay in the tissue compartment for various periods of time, depending ...
Higuchi R, Bowman B, Freiberger M, Ryder OA, Wilson AC.To determine whether DNA survives and can be recovered from the remains of extinct creatures, we have examined dried muscle from a museum specimen of the quagga, a zebra-like species (Equus quagga) that became extinct in 1883 (ref. 1). We report that DNA was extracted from this tissue in amounts approaching 1% of that expected from fresh muscle, and that the DNA was of relatively low molecular weight. Among the many clones obtained from the quagga DNA, two containing pieces of mitochondrial DNA (mtDNA) were sequenced. These sequences, comprising 229 nucleotide pairs, differ by 12 base substitu...
Frisbie DD, Oxford JT, Southwood L, Trotter GW, Rodkey WG, Steadman JR, Goodnight JL, McIlwraith CW.The current study investigated healing of large full-thickness articular cartilage defects during the first 8 weeks with and without penetration of the subchondral bone using microfracture in an established equine model of cartilage healing. Chondral defects in the weightbearing portion of the medial femoral condyle were made bilaterally; one defect in each horse was microfractured whereas the contralateral leg served as the control. The expression of cartilage extracellular matrix components (Types I and II collagen and aggrecan) was evaluated using histologic techniques, reverse transcriptio...
Schnabel LV, Mohammed HO, Miller BJ, McDermott WG, Jacobson MS, Santangelo KS, Fortier LA.Platelet rich plasma (PRP) has recently been investigated for use in tissue regeneration studies that seek to utilize the numerous growth factors released from platelet alpha-granules. This study examined gene expression patterns, DNA, and collagen content of equine flexor digitorum superficialis tendon (SDFT) explants cultured in media consisting of PRP and other blood products. Blood and bone marrow aspirate (BMA) were collected from horses and processed to obtain plasma, PRP, and platelet poor plasma (PPP). IGF-I, TGF-beta1, and PDGF-BB were quantified in all blood products using ELISA. Ten...
Thorpe CT, Udeze CP, Birch HL, Clegg PD, Screen HR.Tendons transfer force from muscle to bone. Specific tendons, including the equine superficial digital flexor tendon (SDFT), also store and return energy. For efficient function, energy-storing tendons need to be more extensible than positional tendons such as the common digital extensor tendon (CDET), and when tested in vitro have a lower modulus and failure stress, but a higher failure strain. It is not known how differences in matrix organization contribute to distinct mechanical properties in functionally different tendons. We investigated the properties of whole tendons, tendon fascicles ...
Caliari SR, Harley BA.Current surgical and tissue engineering approaches for treating tendon injuries have shown limited success, suggesting the need for new biomaterial strategies. Here we describe the development of an anisotropic collagen-glycosaminoglycan (CG) scaffold and use of growth factor supplementation strategies to create a 3D platform for tendon tissue engineering. We fabricated cylindrical CG scaffolds with aligned tracks of ellipsoidal pores that mimic the native physiology of tendon by incorporating a directional solidification step into a conventional lyophilization strategy. By modifying the freez...
McIlwraith CW, Frisbie DD, Rodkey WG, Kisiday JD, Werpy NM, Kawcak CE, Steadman JR.This study evaluated intra-articular injection of bone marrow-derived mesenchymal stem cells (BMSCs) to augment healing with microfracture compared with microfracture alone. Methods: Ten horses (aged 2.5 to 5 years) had 1-cm2 defects arthroscopically created on both medial femoral condyles of the stifle joint (analogous to the human knee). Defects were debrided to subchondral bone followed by microfracture. One month later, 1 randomly selected medial femorotibial joint in each horse received an intra-articular injection of either 20 × 10(6) BMSCs with 22 mg of hyaluronan or 22 mg of hyalurona...
Hauck SM, Dietter J, Kramer RL, Hofmaier F, Zipplies JK, Amann B, Feuchtinger A, Deeg CA, Ueffing M.Autoimmune uveitis is a blinding disease presenting with autoantibodies against eye-specific proteins as well as autoagressive T cells invading and attacking the immune-privileged target tissue retina. The molecular events enabling T cells to invade and attack the tissue have remained elusive. Changes in membrane protein expression patterns between diseased and healthy stages are especially interesting because initiating events of disease will most likely occur at membranes. Since disease progression is accompanied with a break-down of the blood-retinal barrier, serum-derived proteins mask the...
Wilke MM, Nydam DV, Nixon AJ.Mesenchymal stem cells (MSCs) provide an important source of pluripotent cells for musculoskeletal tissue repair. This study examined the impact of MSC implantation on cartilage healing characteristics in a large animal model. Twelve full-thickness 15-mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by injection of a self-polymerizing autogenous fibrin vehicle containing mesenchymal stem cells, or autogenous fibrin alone in control joints. Arthroscopic second look and defect biopsy was obtained at 30 days, and all animals were euthanized 8 month...
McCarthy HE, Bara JJ, Brakspear K, Singhrao SK, Archer CW.A chondrocyte progenitor population isolated from the surface zone of articular cartilage presents a promising cell source for cell-based cartilage repair. In this study, equine articular cartilage progenitor cells (ACPCs) and equine bone marrow-derived stromal cells (BMSCs) were compared as potential cell sources for repair. Clonally derived BMSCs and ACPCs demonstrated expression of the cell fate selector gene, Notch-1, and the putative stem cell markers STRO-1, CD90 and CD166. Chondrogenic induction revealed positive labelling for collagen type II and aggrecan. Collagen type X was not detec...
Lomas AJ, Ryan CN, Sorushanova A, Shologu N, Sideri AI, Tsioli V, Fthenakis GC, Tzora A, Skoufos I, Quinlan LR, O'Laighin G, Mullen AM, Kelly JL....Tendon injuries represent a significant clinical burden on healthcare systems worldwide. As the human population ages and the life expectancy increases, tendon injuries will become more prevalent, especially among young individuals with long life ahead of them. Advancements in engineering, chemistry and biology have made available an array of three-dimensional scaffold-based intervention strategies, natural or synthetic in origin. Further, functionalisation strategies, based on biophysical, biochemical and biological cues, offer control over cellular functions; localisation and sustained relea...
Angele P, Abke J, Kujat R, Faltermeier H, Schumann D, Nerlich M, Kinner B, Englert C, Ruszczak Z, Mehrl R, Mueller R.Collagen-based scaffolds are appealing products for the repair of cartilage defects using tissue engineering strategies. The present study investigated the species-related differences of collagen scaffolds with and without 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS)-crosslinking. Resistance against collagenase digestion, swelling ratio, amino acid sequence, shrinkage temperature, ultrastructural matrix morphology, crosslinking density and stress-strain characteristics were determined to evaluate the physico-chemical properties of equine- and bovine-collagen...
Worster AA, Brower-Toland BD, Fortier LA, Bent SJ, Williams J, Nixon AJ.This study evaluated chondrogenesis of mesenchymal progenitor stem cells (MSCs) cultured initially under pre-confluent monolayer conditions exposed to transforming growth factor-beta1 (TGF-beta1), and subsequently in three-dimensional cultures containing insulin-like growth factor I (IGF-I). Bone marrow aspirates and chondrocytes were obtained from horses and cultured in monolayer with 0 or 5 ng of TGF-beta 1 per ml of medium for 6 days. TGF-beta 1 treated and untreated cultures were distributed to three-dimensional fibrin disks containing 0 or 100 ng of IGF-I per ml of medium to establish fou...
Gaspar D, Spanoudes K, Holladay C, Pandit A, Zeugolis D.The last decade has seen significant developments in cell therapies, based on permanently differentiated, reprogrammed or engineered stem cells, for tendon injuries and degenerative conditions. In vitro studies assess the influence of biophysical, biochemical and biological signals on tenogenic phenotype maintenance and/or differentiation towards tenogenic lineage. However, the ideal culture environment has yet to be identified due to the lack of standardised experimental setup and readout system. Bone marrow mesenchymal stem cells and tenocytes/dermal fibroblasts appear to be the cell populat...
Voga M, Adamic N, Vengust M, Majdic G.Regenerative medicine is a branch of medicine that develops methods to grow, repair, or replace damaged or diseased cells, organs or tissues. It has gained significant momentum in recent years. Stem cells are undifferentiated cells with the capability to self-renew and differentiate into tissue cells with specialized functions. Stem cell therapies are therefore used to overcome the body's inability to regenerate damaged tissues and metabolic processes after acute or chronic insult. The concept of stem cell therapy was first introduced in 1991 by Caplan, who proposed that massive differentiatio...
Cooper KL, Sears KE, Uygur A, Maier J, Baczkowski KS, Brosnahan M, Antczak D, Skidmore JA, Tabin CJ.A reduction in the number of digits has evolved many times in tetrapods, particularly in cursorial mammals that travel over deserts and plains, yet the underlying developmental mechanisms have remained elusive. Here we show that digit loss can occur both during early limb patterning and at later post-patterning stages of chondrogenesis. In the 'odd-toed' jerboa (Dipus sagitta) and horse and the 'even-toed' camel, extensive cell death sculpts the tissue around the remaining toes. In contrast, digit loss in the pig is orchestrated by earlier limb patterning mechanisms including downregulation of...
Koch TG, Heerkens T, Thomsen PD, Betts DH.There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC) have been isolated from fresh umbilical cord blood of humans collected non-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low. The...
Kisiday JD, Kopesky PW, Evans CH, Grodzinsky AJ, McIlwraith CW, Frisbie DD.Bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived progenitor cells (ADPCs) are potential alternatives to autologous chondrocytes for cartilage resurfacing strategies. In this study, the chondrogenic potentials of these cell types were compared by quantifying neo-tissue synthesis and assaying gene expression and accumulation of extracellular matrix (ECM) components of cartilage. Adult equine progenitor cells encapsulated in agarose or self-assembling peptide hydrogels were cultured in the presence or absence of TGFbeta1 for 3 weeks. In BM-MSCs-seeded hydrogels, TGFbeta1 stimulate...
White LM, Sussman MS, Hurtig M, Probyn L, Tomlinson G, Kandel R.To prospectively assess T2 mapping characteristics of normal articular cartilage and of cartilage at sites of arthroscopic repair, including comparison with histologic results and collagen organization assessed at polarized light microscopy (PLM). Methods: Study protocol was compliant with the Canadian Council on Animal Care Guidelines and approved by the institutional animal care committee. Arthroscopic osteochondral autograft transplantation (OAT) and microfracture arthroplasty (MFx) were performed in knees of 10 equine subjects (seven female, three male; age range, 3-5 years). A site of art...
Malda J, Benders KE, Klein TJ, de Grauw JC, Kik MJ, Hutmacher DW, Saris DB, van Weeren PR, Dhert WJ.Articular cartilage defects are common after joint injuries. When left untreated, the biomechanical protective function of cartilage is gradually lost, making the joint more susceptible to further damage, causing progressive loss of joint function and eventually osteoarthritis (OA). In the process of translating promising tissue-engineering cartilage repair approaches from bench to bedside, pre-clinical animal models including mice, rabbits, goats, and horses, are widely used. The equine species is becoming an increasingly popular model for the in vivo evaluation of regenerative orthopaedic ap...
Vidal MA, Kilroy GE, Johnson JR, Lopez MJ, Moore RM, Gimble JM.To characterize equine bone marrow (BM)-derived mesenchymal stem cell (MSC) growth characteristics and frequency as well as their adipogenic and osteogenic differentiation potential. Methods: In vitro experimental study. Methods: Foals (n=3, age range, 17-51 days) and young horses (n=5, age range, 9 months to 5 years). Methods: Equine MSCs were harvested and isolated from sternal BM aspirates and grown up to passage 10 to determine cell-doubling (CD) characteristics. Limit dilution assays were performed on primary and passaged MSCs to determine the frequency of colony-forming units with a fibr...
Vidal MA, Robinson SO, Lopez MJ, Paulsen DB, Borkhsenious O, Johnson JR, Moore RM, Gimble JM.To compare the chondrogenic potential of adult equine mesenchymal stem cells derived from bone marrow (MSCs) or adipose tissue (ASCs). Methods: In vitro experimental study. Methods: Adult Thoroughbred horses (n=11). Methods: BM (5 horses; mean [+/-SD] age, 4+/-1.4 years) or adipose tissue (6 horses; mean age, 3.5+/-1.1 years) samples were obtained. Cryopreserved MSCs and ASCs were used for pellet cultures in stromal medium (C) or induced into chondrogenesis+/-transforming growth factor-3 (TGFbeta(3)) and bone morphogenic factor-6 (BMP-6). Pellets harvested after 3, 7, 14, and 21 days were exam...
Thorpe CT, Peffers MJ, Simpson D, Halliwell E, Screen HR, Clegg PD.Tendon is a simple aligned fibre composite, consisting of collagen-rich fascicles surrounded by a softer interfascicular matrix (IFM). The composition and interactions between these material phases are fundamental in ensuring tissue mechanics meet functional requirements. However the IFM is poorly defined, therefore tendon structure-function relationships are incompletely understood. We hypothesised that the IFM has a more complex proteome, with faster turnover than the fascicular matrix (FM). Using laser-capture microdissection and mass spectrometry, we demonstrate that the IFM contains more ...
Toupadakis CA, Wong A, Genetos DC, Cheung WK, Borjesson DL, Ferraro GL, Galuppo LD, Leach JK, Owens SD, Yellowley CE.To determine the optimal osteogenic source of equine mesenchymal stem cells (eMSCs) and optimize collection of and expansion conditions for those cells. Methods: 10 adult Quarter Horses and 8 newborn Thoroughbred foals. Methods: eMSCs were isolated from bone marrow (BM), adipose tissue, and umbilical cord blood and tissue, and the osteogenic potential of each type was assessed. Effects of anatomic site, aspiration volume, and serum type on eMSC yield from BM were investigated. Results: BM-eMSCs had the highest overall expression of the osteogenic genes Cbfa1, Osx, and Omd and staining for ALP ...
Bi X, Yang X, Bostrom MP, Camacho NP.Significant complications in the management of osteoarthritis (OA) are the inability to identify early cartilage changes during the development of the disease, and the lack of techniques to evaluate the tissue response to therapeutic and tissue engineering interventions. In recent studies several spectroscopic parameters have been elucidated by Fourier transform infrared imaging spectroscopy (FT-IRIS) that enable evaluation of molecular and compositional changes in human cartilage with progressively severe OA, and in repair cartilage from animal models. FT-IRIS permits evaluation of early-stag...
Bi X, Li G, Doty SB, Camacho NP.The orientation of collagen molecules is an important determinant of their functionality in connective tissues. The objective of the current study is to establish a method to determine the alignment of collagen molecules in histological sections of cartilage by polarized Fourier transform infrared imaging spectroscopy (FT-IRIS), a method based on molecular vibrations. Methods: Polarized FT-IRIS data obtained from highly oriented tendon collagen were utilized to calibrate the derived spectral parameters. The ratio of the integrated areas of the collagen amide I/II absorbances was used as an ind...
Carter CA, Jolly DG, Worden CE, Hendren DG, Kane CJ.Nonhealing wounds of the lower equine limb represent a challenging model. The platelet is a natural source of a myriad of growth factors and cytokines that promote wound healing. This study evaluates the potential of platelet derived factors to enhance wound healing in the lower equine limb. Platelets were isolated from horse blood and activated with thrombin, a process known to induce growth factor release. This produced a platelet gel composed of platelet-rich plasma (PRP). To test this all-natural wound healant, 2.5-cm(2) full thickness cutaneous wounds were created below the knee and hock ...
Mansfield J, Yu J, Attenburrow D, Moger J, Tirlapur U, Urban J, Cui Z, Winlove P.A combination of two-photon fluorescence (TPF), second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) imaging has been used to investigate the elastin fibre network in healthy equine articular cartilage from the metacarpophalangeal joint. The elastin fibres were identified using their intrinsic two-photon fluorescence and immuno-staining was used to confirm the identity of these fibres. SHG was used to reveal the collagen matrix and the collagen fibre orientations were determined from their SHG polarization sensitivity, while CARS was used to clearly delineate the c...
Torricelli P, Fini M, Filardo G, Tschon M, Pischedda M, Pacorini A, Kon E, Giardino R.Tissue repair in musculoskeletal injuries is often a slow and sometimes incomplete process. Regenerative medicine based on the use of growth factors (GFs) and cell therapy is aimed at improving the quality and speed of tendon and ligament healing. The aim of this study was to evaluate the potential for the administration of a combination of autologous platelet-rich plasma (PRP) and freshly isolated bone marrow mononucleated cells (BMMNCs) in 13 competition horses affected by overuse musculoskeletal injuries (suspensory ligament desmopathy and superficial flexor tendinopathy) and refractory to ...
