Growth factors are naturally occurring proteins or peptides that play a significant role in regulating cellular growth, proliferation, and differentiation in horses. These factors are involved in various physiological processes, including tissue repair, development, and immune function. Common growth factors studied in equine research include insulin-like growth factor (IGF), transforming growth factor-beta (TGF-β), and fibroblast growth factor (FGF). Their expression and activity can influence wound healing, musculoskeletal development, and recovery from injury. This page compiles peer-reviewed research studies and scholarly articles that examine the role, regulation, and clinical significance of growth factors in equine biology and health.
Abd El-Rahman SS, Amer MS, Hassan MH, Fahmy HM, Shamaa AA.Lyophilized equine platelet derived growth factors (LGF) is a novel advanced platelet rich protein growth factor. It has been successfully applied in various fields of regenerative medicine to treat a variety of inflammatory and degenerative musculoskeletal conditions. Our study aimed to evaluate the efficacy of intraarticularly injected LGF for the remedy of articular cartilage injury, commonly characterized by progressive pain and loss of joint function in osteoarthritic rabbits. Full-thickness cylindrical cartilage defects were generated in both femoral condylar articular surfaces in twenty...
Fukuda K, Kuroda T, Tamura N, Mita H, Miyata H, Kasashima Y.This study aimed to verify the effects of platelet lysate (PL) administration on the repair of injured horse tissue. Skeletal muscle injuries were induced in 26 Thoroughbreds by bupivacaine administration. PL or saline was administered 1 day (1D) after injury. Muscle samples from 22 horses injected with PL or saline were obtained by needle biopsy at 2, 3, 4, or 7 days (2D, 3D, 4D, or 7D, respectively) after injury, and growth-factor concentrations and muscle regeneration-associated gene expression levels were determined. Intact samples were similarly collected before injury, and samples of inj...
Colombo I, Mislei B, Mari G, Iacono E, Merlo B.Many mares are susceptible to persistent mating-induced endometritis (PMIE), an important cause of reduced fertility. Platelet lysate (PL) derives from freeze-thawing platelets after concentration, so that growth factors are released from the platelets. Among the advantages of PL compared to platelet-rich plasma (PRP), it can be frozen stored and allogenic use for PL might also be conceivable. Platelet-rich plasma beneficially reduced inflammatory response in PMIE mares when administered 24 h pre- or 4 h post-AI. The aim of this study was to test the effect of PL on inflammatory uterine resp...
Rogers CW, Gee EK, Dittmer KE.Within the lay literature, and social media in particular, there is often debate about the age at which a horse should be started and introduced to racing or sport. To optimize the welfare and longevity of horses in racing and sport, it is important to match exercise with musculoskeletal development and the ability of the musculoskeletal system to respond to loading. The justification for not exercising horses at a certain age is often in contrast to the scientific literature and framed, with incorrect generalizations, with human growth. This review provides a relative comparison of the growth...
Roberts JH, Halper J.Repair and healing of injured and diseased tendons has been traditionally fraught with apprehension and difficulties, and often led to rather unsatisfactory results. The burgeoning research field of growth factors has opened new venues for treatment of tendon disorders and injuries, and possibly for treatment of disorders of the aorta and major arteries as well. Several chapters in this volume elucidate the role of transforming growth factor β (TGFß) in pathogenesis of several heritable disorders affecting soft tissues, such as aorta, cardiac valves, and tendons and ligaments. Several member...
Li XB, Huang XX, Zang CJ, Ma C, Chen KX, Zhao GD, Li Q, Li XY, Zhang WJ, Yang KL.There is little objective information concerning the effect of steam-flaked grains on foal's growth performance and faecal microbiota. To determine the effects of steam-flaked grains on foal's growth performance and faecal microbiota, faecal samples were collection from 18 foals which had been fed either corn, oat or barley diets over the 60 days of the experiment. Body weight and conformation measurements were collected. Next-generation sequencing of the V3 + V4 region of the 16 S rRNA gene was used to assess the microbial composition of faeces. Alpha diversity, Venn graph, Relative abun...
Haspeslagh M, Van Hecke LL, Hermans K, Chiers K, Pint E, Wilmink JM, Martens AM.Distal limb wounds in horses often show aberrant healing due to a slow inflammatory response. In human medicine, negative pressure wound therapy (NPWT) is used for the treatment of chronic wounds with a similar inflammatory response. Objective: To compare the effect of NPWT to calcium alginate dressings on the healing of (non) contaminated equine distal limb wounds. Methods: Controlled experiment. Methods: Circular wounds were created on the left and right dorsomedial metacarpus of 10 horses. In five horses, the wounds were contaminated with Staphylococcus aureus and Pseudomonas aeruginosa. In...
Zanotto GM, Liesbeny P, Barrett M, Zlotnick H, Frank E, Grodzinsky AJ, Frisbie DD.Microfracture augmentation can be a cost-effective single-step alternative to current cartilage repair techniques. Trypsin pretreatment combined with a growth factor-functionalized self-assembling KLD hydrogel ("functionalized hydrogel") has been shown to improve overall cartilage repair and integration to surrounding tissue in small animal models of osteochondral defects. Microfracture combined with trypsin treatment and a functionalized hydrogel will improve reparative tissue quality and integration as compared with microfracture alone in an equine model. Controlled laboratory study. Bilater...
Zayed M, Adair S, Dhar M.Synovial fluid contains cytokines, growth factors and resident mesenchymal stem cells (MSCs). The present study aimed to (1) determine the effects of autologous and allogeneic synovial fluid on viability, proliferation and chondrogenesis of equine bone marrow MSCs (BMMSCs) and (2) compare the immunomodulatory properties of equine synovial fluid MSCs (SFMSCs) and BMMSCs after stimulation with interferon gamma (INF-γ). To meet the first aim of the study, the proliferation and viability of MSCs were evaluated by MTS and calcein AM staining assays. To induce chondrogenesis, MSCs were cultured in ...
Di Stefano DA, Vinci R, Capparè P, Gherlone EF.Enzyme-deantigenic equine bone (EDEB) is a substitute of autogenous bone. Mixing it with plasma rich in growth factors (PRGF) seems a viable option to achieve enhanced bone formation in alveolar bone augmentation surgeries. This retrospective study aims to first report the histomorphometric and clinical outcomes achieved when using the EDEB/PRGF mixture for performing sinus augmentation procedures followed by delayed implant placement. Records of 11 patients who underwent 14 sinus augmentation surgeries using EDEB/PRGF followed by delayed implant placement were retrospectively collected and an...
Hendesi H, Stewart S, Gibison ML, Guehring H, Richardson DW, Dodge GR.Posttraumatic osteoarthritis is a disabling condition impacting the mostly young and active population. In the present study, we investigated the impact of intra-articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of microfracture treatment, a widely used surgical technique to enhance cartilage healing at the site of injury. For this study, we created a cartilage defect and performed microfracture treatment in fetlock joints of 18 horses, treated joints with one of three doses of sprifermin (10, 30, or 100 μg) or with saline, hyaluronan, and evaluated a...
Pezzanite L, Chow L, Griffenhagen G, Dow S, Goodrich L.Culture and expansion of equine mesenchymal stromal cells (MSCs) are routinely performed using fetal bovine serum (FBS) as a source of growth factors, nutrients, and extracellular matrix proteins. However, the desire to minimize introduction of xenogeneic bovine proteins or pathogens and to standardize cellular products intended for clinical application has driven evaluation of alternatives to FBS. Replacement of FBS in culture for several days before administration has been proposed to reduce antigenicity and potentially prolong survival after injection. However, the functional consequences o...
Dawod A, Miro J, Elbaz HT, Fahmy H, Abdoon AS.This study was designed to examine the effect of the intrauterine infusion of platelet-rich plasma (PRP) or equine lyophilized growth factor (L-GFequina) on the follicular growth, endometrial thickness, estrus cycle length, and pregnancy rate in purebred Arabian mares. A total of 73 purebred Arabian mares who experienced repeat breeding for three successive cycles were randomly divided into the following three groups: control group, without treatment; second Group (PRP group), in which mares were intrauterine infused with 20 mL of fresh PRP on the second day after the end of physic estrus phas...
Pinto-Bravo P, Rebordão MR, Amaral A, Fernandes C, Galvão A, Silva E, Pessa-Santos P, Alexandre-Pires G, Roberto da Costa RP, Skarzynski DJ....The oviduct presents the ideal conditions for fertilization and early embryonic development. In this study, (i) vascularization pattern; (ii) microvascular density; (iii) transcripts of angiogenic factors (, , ) and their receptors-, , , respectively, and (iv) the relative protein abundance of those receptors were assessed in cyclic mares' oviducts. The oviductal artery, arterioles and their ramifications, viewed by means of vascular injection-corrosion, differed in the infundibulum, ampulla and isthmus. The isthmus, immunostained with CD31, presented the largest vascular area and the highest ...
Hagen A, Lehmann H, Aurich S, Bauer N, Melzer M, Moellerberndt J, Patané V, Schnabel CL, Burk J.Translation of multipotent mesenchymal stromal cell (MSC)-based therapies is advancing in human and veterinary medicine. One critical issue is the culture of MSC before clinical use. Using fetal bovine serum (FBS) as supplement to the basal medium is still the gold standard for cultivation of many cell types including equine MSC. Alternatives are being explored, with substantial success using platelet lysate-supplemented media for human MSC. However, progress lags behind in the veterinary field. The aim of this study was to establish a scalable protocol for equine platelet lysate (ePL) produc...
Yang F, Richardson DW.The tendon is highly prone to injury, overuse, or age-related degeneration in both humans and horses. Natural healing of injured tendon is poor, and cell-based therapeutic treatment is still a significant clinical challenge. In this study, we extensively investigated the expression of tenogenic genes in equine bone marrow mesenchymal stem cells (BMSCs) and tenocyte-derived induced pluripotent stem cells (teno-iPSCs) stimulated by growth factors (TGF-3 and BMP12) combined with ectopic expression of tenogenic transcription factor MKX or cyclic uniaxial mechanical stretch. Western blotting reveal...
Fukuda K, Kuwano A, Kuroda T, Tamura N, Mita H, Okada Y, Kasashima Y.This study optimized the double-spin conditions for preparing equine platelet-rich plasma (PRP): leukocyte-rich PRP (L-PRP) and leukocyte-poor PRP (P-PRP). Whole blood samples were centrifuged at various double-spin conditions. Both L-PRP and P-PRP were prepared at each stage, and complete blood counts and growth factor concentrations were compared. Samples centrifuged at 160 × 900 g, 160 × 2,000 g, and 400 × 2,000 g exhibited the highest platelet counts. P-PRP had significantly lower leukocyte and erythrocyte contents than L-PRP, especially at 400 × 2,000 g. No significant differences wer...
Bagge J, MacLeod JN, Berg LC. Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stem cells (MSCs) are used increasingly for autologous cell therapy in equine practice to treat musculoskeletal and other injuries. Current recommendations often call for 10-100 million MSCs per treatment, necessitating the expansion of primary cells in culture prior to therapeutic use. Of concern, human and rodent studies have shown a decline of both MSC recovery from sampled tissue and proliferative capacity with increasing donor age. This may be problematic for applications of autologous cell-based therapies in the important eq...
McCoy AM, Kemper AM, Boyce MK, Brown MP, Trumble TN.Post-traumatic osteoarthritis (PTOA) is a common and significant problem in equine athletes. It is a disease of the entire joint, with the synovium thought to be a key player in disease onset and progression due to its role in inflammation. The development of effective tools for early diagnosis and treatment of PTOA remains an elusive goal. Altered gene expression represents the earliest discernable disease-related change, and can provide valuable information about disease pathogenesis and identify potential therapeutic targets. However, there is limited work examining global gene expression c...
Kendall A, Nyström S, Ekman S, Hultén LM, Lindahl A, Hansson E, Skiöldebrand E.Nerve growth factor (NGF) is a neurotrophin with many functions. In humans, it is involved in inflammation, nerve growth, apoptosis and pain signalling. Increased concentrations of NGF in synovial fluid has been shown in humans and dogs with osteoarthritis. Despite osteoarthritis being a common problem in horses, no studies have previously been published on NGF in the equine joint. The aim of this study was to quantify NGF in equine synovial fluid from healthy joints, acutely inflamed septic joints and joints with structural changes associated with osteoarthritis. A secondary aim was to identi...
Menarim BC, Gillis KH, Oliver A, Ngo Y, Werre SR, Barrett SH, Rodgerson DH, Dahlgren LA.Synovitis is a major component of osteoarthritis and is driven primarily by macrophages. Synovial macrophages are crucial for joint homeostasis (M2-like phenotype), but induce inflammation (M1-like) when regulatory functions become overwhelmed. Macrophage phenotypes in synovium from osteoarthritic and healthy joints are poorly characterized; however, comparative knowledge of their phenotypes during health and disease is paramount for developing targeted treatments. This study compared patterns of macrophage activation in healthy and osteoarthritic equine synovium and correlated histology with ...
Packard GC.I re-examined published data for ontogenetic change in relative mass of the brain in six species of mammal (i.e., sheep, pig, cow, horse, rat, cat) to illustrate an insidious problem with conventional analyses of brain-body allometry. Graphical displays of logarithmic transformations of the original data for each species give the appearance of two discrete mathematical distributions, but untransformed observations nonetheless conform to a single distribution that is well described by a single, nonlinear equation. The concept of biphasic, allometric growth by the brain consequently is an artifa...
Haythorn A, Young M, Stanton J, Zhang J, Mueller POE, Halper J.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-β (TGFβ) family, impacting synthesis of proteoglyca...
Pennati A, Apfelbeck T, Brounts S, Galipeau J.Mammalian platelets participate in the immediate tissue injury response by initiating coagulation and further promoting tissue injury mitigation and repair. The latter properties are deployed following platelet release of presynthetized morphogens, cytokines, and growth and chemotactic factors, which launch a tissue regenerative, angiogenic, and anti-inflammatory program. Several blood-derived biologic products, like platelet-rich plasma (PRP) and platelet lysate (PL), are currently on the market to allow proper healing and tissue regeneration. However, not all growth factors are released from...
Javanshir S, Younesi Soltani F, Dowlati G, Parham A, Naderi-Meshkin H.Managing tendon healing process is complicated mainly due to the limited regeneration capacity of tendon tissue. Mesenchymal stem cells (MSCs) have potential applications in regenerative medicine and have been considered for tendon repair and regeneration. This study aimed to evaluate the capacity of equine adipose tissue-derived cells (eASCs) to differentiate into tenocytes in response to platelet-derived growth factor-BB (PDGF-BB) and growth differentiation factor-6 (GDF-6) in vitro. Frozen characterized eASCS of 3 mares were thawed and the cells were expanded in basic culture medium (DMEM...
Satué K, Fazio E, Cravana C, Quartuccio M, Marcilla M, Medica P.The aim of the study was to assess the physiological reference values for systemic and intrafollicular placental growth factor (PlGF) concentrations in different categories of follicular sizes in cycling mares, according to progesterone (P4) and oestradiol (E2) patterns. Sixty ovaries were taken after slaughter from 30 clinically healthy mares. Regarding their size, the follicles were classified into three different categories, i.e. small (20-30 mm), medium-sized (31-40 mm) and large (≥41 mm), and follicular fluid (FF) was sampled from each single follicle. Intrafollicular PlGF concentration...
Fukuda K, Kuroda T, Tamura N, Mita H, Kasashima Y.Platelet-rich plasma (PRP) therapy has been widely applied in various medical fields including humans and horses. This study aimed to establish an optimal activation method to stably and reproducibly maximize the concentrations of platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-β1 (TGF-β1) contained in equine PRP. Autologous PRP was prepared from 11 Thoroughbreds. For the activation test, PRP was activated by either a single freeze-thaw cycle (Fr) or adding calcium and autologous serum containing thrombin (Ca). PDGF-BB and TGF-β1 concentrations in Fr, Ca, nonactiv...
Peters S, Wilson J, Boyette J.The objective of this study was to determine the influence of age on expression of insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein (IGFBP5), myostatin (MSTN), and myosin (MYH1) genes which are related to growth and muscle development in the American Quarter Horse. Thus, horses (n = 10) from weanling, yearling, 2-, 3-, and 10-year-old age classes were sampled and gene expression was assessed by RT-qPCR. ΔC was calculated using the hypoxanthine-guanine phosphoribosyltransferase gene as an internal normalizer. The generalized linear model was used to determine di...
Aimaletdinov A, Mindubaeva G, Khalikova S, Kabwe E, Salmakova A, Alexandrova N, Rutland C, Rizvanov A, Zakirova E.Tendon injuries are one of the most common causes of orthopedic disorders in horses. Such injuries involve a long course of treatment and recovery. The most promising method of treating these injuries is the use of recombinant proteins and gene therapy. In this work, we evaluated the therapeutic efficacy of plasmid DNA (pDNA) containing two species-specific coding sequences, i.e. vascular endothelial growth factor 164 (VEGF164) and fibroblast growth factor 2 (FGF2), in the treatment of severe damage to the tendon of the superficial digital flexor. A pDNA construct was used to restore the damag...
Marques-Smith P, Kallerud AS, Johansen GM, Boysen P, Jacobsen AM, Reitan KM, Henriksen MM, Löfgren M, Fjordbakk CT.Biologic' therapies, such as autologous conditioned serum (ACS), are gaining popularity in treating orthopaedic conditions in equine veterinary medicine. Evidence is scarce regarding ACS constituents, and large inter-individual differences in cytokine and growth factor content have been demonstrated. The objective of the current study was to investigate the potential association between cytokine and growth factor content of ACS and clinical effect in harness racehorses with spontaneously occurring low-grade articular lameness. Horses received 3 intra-articular injections of ACS administered at...
Gomiero C, Bertolutti G, Martinello T, Van Bruaene N, Broeckx SY, Patruno M, Spaas JH.Tendons regenerate poorly due to a dense extracellular matrix and low cellularity. Cellular therapies aim to improve tendon repair using mesenchymal stem cells and tenocytes; however, a current limitation is the low proliferative potential of tenocytes in cases of severe trauma. The purpose of this study was to develop a method useful in veterinary medicine to improve the differentiation of Peripheral Blood equine mesenchymal stem cells (PB-MSCs) into tenocytes. PB-MSCs were used to study the effects of the addition of some growth factors (GFs) as TGFβ3 (transforming growth factor), EGF2 (Epi...
Equine sarcoids are benign fibroblastic skin tumours that are recognized throughout the world. Infection with bovine papillomavirus (BPV) types 1 and 2 has been implicated as a major factor in disease development; however, the cellular mechanisms underlying fibroblast transformation remain poorly defined. The present study further characterizes aspects of the association with BPV in 15 equine sarcoids. BPV DNA was demonstrated in 12/15 tumours collected from different areas of Italy. Nine of these 12 tumours expressed the BPV oncoproteins E5 and E7, but these oncoproteins were not expressed by...
Castelijns G, Crawford A, Schaffer J, Ortolano GA, Beauregard T, Smith RK.Platelet preparations have become a treatment for soft tissue injuries in horses. This study evaluated a novel filter-based system to concentrate platelets and assesses its value in the treatment of suspensory ligament branch desmitis. Methods: Filtered platelet concentrate was prepared from 55 ml of venous blood obtained from 21 normal horses. Platelets and white blood cells in whole blood and filtered platelet concentrate were measured, as was platelet activating factor (PAF)-induced platelet-derived growth factor-BB (PDGF-BB) release. Eleven horses with 18 focal acute suspensory ligament br...
Nauwelaerts S, Malone SR, Clayton HM.This study used stabilographic analysis to measure and describe changes in stability during standing in foals from birth to 5 months of age. Stabilographic analysis was performed on newborn foals immediately after first suckling then daily until 1 week of age, weekly until 1 month of age and monthly until 5 months of age. Ground reaction force (GRF) data were collected for periods of 8s with the foal standing on one or two force plates recording at 1000 Hz. Stabilographic variables describing the amplitude, velocity and frequency of center of pressure (COP) movements were derived from the GRF ...
Maciel FB, DeRossi R, Módolo TJ, Pagliosa RC, Leal CR, Delben AA.Deep second-degree burns (DSDb) involve all epidermis layers, including the basal laminae. In general, DSDb heals with extensive areas of scarring. Platelet-rich plasma (PRP) is a source of growth factors, obtained by centrifugation and addition of thrombin and calcium, resulting in a gel. The objective of this study was to monitor the healing of DSDb by sequential biopsies after PRP treatment and evaluating by a scanning electron microscopy. Also, characterize bacterial profile and PRP antibacterial effect in horses' burns. Four horses were placed into two groups, G1 and G2, with the groups r...
Theoret CL, Barber SM, Moyana TN, Gordon JR.To map the expression of transforming growth factor (TGF)-beta(1), TGF-beta(3), and basic fibroblast growth factor (bFGF) in full-thickness skin wounds of the horse. To determine whether their expression differs between limbs and thorax, to understand the pathogenesis of exuberant granulation tissue. Methods: Six wounds were created on one lateral metacarpal area and one midthoracic area of each horse. Sequential wound biopsies allowed comparison of the temporal expression of growth factors between limb and thoracic wounds. Methods: Four 2- to 4-year-old horses. Methods: Wounds were assessed g...
Holopainen JT, Brama PA, Halmesmäki E, Harjula T, Tuukkanen J, van Weeren PR, Helminen HJ, Hyttinen MM.The effects of growth and maturation on the mineral deposition and the collagen framework of equine subchondral bone (SCB) were studied. Methods: Osteochondral specimens (diameter 6 mm) from the left metacarpophalangeal joint of 5-(n=8), 11-(n=8) and 18-month-old (n=6) horses were investigated at two differently loaded sites (Site 1 (S1): intermittent peak loading; Site 2 (S2): habitual loading). The SCB mineral density (BMD) was measured with peripheral quantitative computer tomography (pQCT), and the data were adjusted against the volume fraction (Vv) of the bone extracellular matrix (ECM). ...
Kasashima Y, Smith RK, Birch HL, Takahashi T, Kusano K, Goodship AE.Most skeletal tissues are thought to adapt to the mechanical environment they experience. While this has been demonstrated for muscle and bone, previous studies in the mature horse have failed to demonstrate adaptation in the superficial digital flexor tendon (SDFT), which suffers a high frequency of injury. This study tested the hypothesis that imposed exercise during growth would result in an increase in SDFT cross-sectional area (CSA). Fourteen Thoroughbred foals were divided into 2 sex-matched groups. A control group received 4 h pasture exercise and an exercise group had the same amount o...
Mitchell A, Rivas KA, Smith R, Watts AE.Equine superficial digital flexor tendon injury is a well-accepted model of human tendon injury and is routinely treated with local injections of autologous mesenchymal stem cells (MSCs). Identification of a clinically safe medium for short-term cryopreservation of MSCs prior to cell implantation would streamline laboratory and clinical procedures for autologous regenerative therapies. Veterinary experience with short-term (MSCs prepared after the injury has occurred) cryopreserved MSCs in naturally occurring injury in the horse will be of value to human practitioners. Methods: Equine bone mar...
Ginther OJ.The nature of selection of the dominant follicle is reviewed by comparing research results between cattle and horses. In both species, emergence of a follicular wave is stimulated by an FSH surge. The surge reaches a peak by the time the follicles attain 4 mm in diameter in cattle and 13 mm in mares. In cattle, all of the growing follicles >/=5 mm contribute to the decline in FSH concentrations. However, the declining FSH concentrations are still needed by the growing follicles. Several days after the peak of the FSH surge and emergence of the wave, the two largest follicles reach means of 8.5...
Branly T, Contentin R, Desancé M, Jacquel T, Bertoni L, Jacquet S, Mallein-Gerin F, Denoix JM, Audigié F, Demoor M, Galéra P.Articular cartilage is a tissue characterized by its poor intrinsic capacity for self-repair. This tissue is frequently altered upon trauma or in osteoarthritis (OA), a degenerative disease that is currently incurable. Similar musculoskeletal disorders also affect horses and OA incurs considerable economic loss for the equine sector. In the view to develop new therapies for humans and horses, significant progress in tissue engineering has led to the emergence of new generations of cartilage therapy. Matrix-associated autologous chondrocyte implantation is an advanced 3D cell-based therapy that...
Theoret CL, Barber SM, Moyana TN, Gordon JR.To determine whether transforming growth factor (TGF)-beta1 and -beta3 expression differs between equine limb wounds healing normally and those healing with experimentally induced exuberant granulation tissue (EGT). Methods: Six wounds were created on the lateral aspect of both metacarpi of each horse; one forelimb was untreated, and the other was bandaged to stimulate the development of EGT. Sequential wound biopsies allowed comparison of growth factor expression between the two types of wound. Methods: Four horses (2 to 4 years of age; 350 to 420 kg). Methods: Wounds were assessed grossly, h...
Scaravaggi I, Borel N, Romer R, Imboden I, Ulbrich SE, Zeng S, Bollwein H, Bauersachs S.Previous endometrial gene expression studies during the time of conceptus migration did not provide final conclusions on the mechanisms of maternal recognition of pregnancy (MRP) in the mare. This called for a cell type-specific endometrial gene expression analysis in response to embryo signals to improve the understanding of gene expression regulation in the context of MRP. Laser capture microdissection was used to collect luminal epithelium (LE), glandular epithelium and stroma from endometrial biopsies from Day 12 of pregnancy and Day 12 of the oestrous cycle. RNA sequencing (RNA-Seq) showe...
Giraldo CE, Álvarez ME, Carmona JU.To compare five activation methods in equine platelet-rich plasma (PRP) by determination of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) concentrations in platelet-rich gel (PRG) supernatants. Methods: Platelet-rich plasma from 20 horses was activated by calcium chloride (CC), calcium gluconate (CG), bovine thrombin (BT), and their combinations, BTCC and BTCG. Both growth factor concentrations in PRG supernatants were measured by ELISA and compared with plasma and platelet lysates (PL) over time. Results: Growth factor concentrations were signific...
Phillips T, Ferraz I, Bell S, Clegg PD, Carter SD, Mobasheri A.Glucose serves as the major energy substrate for articular chondrocytes and as the main precursor for the synthesis of extracellular matrix glycosaminoglycans in cartilage. Chondrocytes have been shown to express several glucose transporter (GLUT) isoforms including GLUT1 and GLUT3. The aim of this investigation was to determine the effects of endocrine and cytokine factors on the capacity of equine articular chondrocytes for transporting 2-deoxy-d-[2,6-3H] glucose and on the expression levels of GLUT1 and GLUT3. Chondrocytes maintained in monolayer culture were stimulated for 24 h with TNF-al...
Goodrich LR, Brower-Toland BD, Warnick L, Robbins PD, Evans CH, Nixon AJ.Insulin-like growth factor-I (IGF-I) is one of the most influential growth factors in cartilage repair. Maintenance of adequate IGF-I levels after articular repair procedures is complicated by the short biological half-life of IGF-I in vivo. This study investigated the potential for more prolonged IGF-I delivery through direct adenoviral mediated transduction of synovial tissues in the metacarpophalangeal (MCP) joints of horses. The use of a large animal model provided a structurally similar and metabolically relevant corollary to the human knee. The complete IGF-I coding sequence was packaged...
Fortier LA, Nixon AJ, Lust G.To assess the effects of supraphysiologic concentrations of insulin-like growth factor-1 (IGF-1) on morphologic and phenotypic responses of chondrocytes. Methods: Articular cartilage obtained from 2 young horses. Methods: Chondrocytes were suspended in fibrin cultures and supplemented with 25, 12.5, or 0 mg of IGF-1/ml of fibrin. Chondrocyte morphology and phenotypic expression were assessed histologically, using H&E and Alcian blue stains, immunoreaction to collagen type I and II, and in situ hybridization. Proteoglycan content, synthesis, and monomer size were analyzed. The DNA content w...
Schröder HJ.The growth of the fetus is determined by substrate supply mostly for mass accretion and energy gain, and by control systems. Experiments with whole animal models will face the following problems: (1) The fetus, like a three compartmental "Russian doll", is at the end of a long supply chain. There are interactions (e.g. hormones) and partitioning of substrates between the compartments. (2) The fetal organism is growing and differentiating at the same time and not in a steady-state. Experimental results thus depend on gestational age. (3) About 75% of animal experiments on fetal growth restricti...
Bussche L, Rauner G, Antonyak M, Syracuse B, McDowell M, Brown AMC, Cerione RA, Van de Walle GR.Signaling mechanisms that regulate mammary stem/progenitor cell (MaSC) self-renewal are essential for developmental changes that occur in the mammary gland during pregnancy, lactation, and involution. We observed that equine MaSCs (eMaSCs) maintain their growth potential in culture for an indefinite period, whereas canine MaSCs (cMaSCs) lose their growth potential in long term cultures. We then used this system to investigate the role of microvesicles (MVs) in promoting self-renewal properties. We found that Wnt3a and Wnt1 were expressed at higher levels in MVs isolated from eMaSCs compared wi...
Plummer CE, Ollivier F, Kallberg M, Brooks D, Barrie K, Utter M, Gelatt K.Amniotic membrane transplantation (AMT) is an effective clinical therapy for reconstruction of the ocular surface in human and veterinary patients. Amnion is avascular and strong, contains antiangiogenic and antiinflammatory properties and growth factors, and has properties that prevent or decrease fibrosis in healing tissue. Indications for its use are steadily growing and include grafting to replace diseased, missing or excised tissue, patching to support diseased tissue during the healing process and as a substrate for the expansion of epithelial cells for transplantation to the cornea. AMT...
Rogers CW, Gee EK, Dittmer KE.Within the lay literature, and social media in particular, there is often debate about the age at which a horse should be started and introduced to racing or sport. To optimize the welfare and longevity of horses in racing and sport, it is important to match exercise with musculoskeletal development and the ability of the musculoskeletal system to respond to loading. The justification for not exercising horses at a certain age is often in contrast to the scientific literature and framed, with incorrect generalizations, with human growth. This review provides a relative comparison of the growth...
Allen WR, Gower S, Wilsher S.Polyclonal antisera for vascular endothelial growth factor (VEGF) and its two main receptor molecules, VEGF-I (Flt) and VEGF-II (KDR), were used in a conventional immunocytochemical staining method to localize these angiogenic ligand molecules in the endometrium and placenta of the mare during the oestrous cycle and pregnancy. The anti-VEGF and anti-Flt sera both labelled the lumenal and glandular epithelia of the endometrium throughout the oestrous cycle and both the invasive trophoblast cells of the endometrial cups and the non-invasive trophoblast of the allantochorion in pregnancy. The ant...
Campos-Chillon F, Farmerie TA, Bouma GJ, Clay CM, Carnevale EM.We hypothesised that advanced mare age is associated with follicle and oocyte gene alterations. The aims of the study were to examine quantitative and temporal differences in mRNA for LH receptor (LHR), amphiregulin (AREG) and epiregulin (EREG) in granulosa cells, phosphodiesterase (PDE) 4D in cumulus cells and PDE3A, G-protein-coupled receptor 3 (GPR3), growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and mitochondrial (mt) DNA in oocytes. Samples were collected from dominant follicles of Young (3-12 years) and Old (≥20 years) mares at 0, 6, 9 and 12h after admi...
López C, Carmona JU, Giraldo CE, Alvarez ME.1) To evaluate the bacteriostatic in vitro effect of pure platelet-rich plasma (P-PRP), pure platelet-rich gel (P-PRG), leukocyte-poor gel (LPG), platelet-poor plasma (PPP), and heat inactivated plasma (IP) against methicillin-sensitive Staphylococcus aureus (MSSA) over a period of 24 hours. 2) To determine the degradation of platelet factor-4 (PF-4), transforming growth factor beta 1 (TGF-β1), and platelet-derived growth factor isoform BB (PDGF-BB) in these equine blood components. 3) To establish correlations between platelet and leukocyte counts, PF-4 concentrations, and MSSA growth. Metho...
Scala M, Lenarduzzi S, Spagnolo F, Trapasso M, Ottonello C, Muraglia A, Barla A, Squillario M, Strada P.The aim of the present study was to evaluate the safety and the clinical outcome of platelet-rich plasma for the treatment of teno-desmic injures in competition horses. Methods: From January 2009 to December 2011, 150 sport horses suffering from teno-desmic injuries were treated with no-gelled platelet-concentrate. Results: No horse showed any major adverse reaction as a result of the procedure. Full healing was obtained for 81% of the horses. Twelve percent had clinical improvement and only 7% a failure. Eight percent of cases of relapse were observed. No statistically significant correlation...
Bagge J, MacLeod JN, Berg LC. Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stem cells (MSCs) are used increasingly for autologous cell therapy in equine practice to treat musculoskeletal and other injuries. Current recommendations often call for 10-100 million MSCs per treatment, necessitating the expansion of primary cells in culture prior to therapeutic use. Of concern, human and rodent studies have shown a decline of both MSC recovery from sampled tissue and proliferative capacity with increasing donor age. This may be problematic for applications of autologous cell-based therapies in the important eq...
Ríos DL, López C, Álvarez ME, Samudio IJ, Carmona JU.Platelet-rich plasma (PRP) preparations are a common treatment in osteoarthritis (OA) and inflammatory synovitis. However, there is ambiguity regarding the ideal concentration of leukocytes and platelets in these preparations necessary to induce an adequate anti-inflammatory and anabolic response in joint tissues, such as the synovial membrane. This research aimed to study, in normal synovial membrane explants (SME) challenged with lipopolysaccharide (LPS), the temporal effects (at 48 and 96h) of leukocyte- and platelet-rich gel (L-PRG) and pure platelet-rich gel (P-PRG) supernatants on the pr...
Smit Y, Marais HJ, Thompson PN, Mahne AT, Goddard A.Osteoarthritis is a common cause of lameness in horses, resulting in poor performance. Intra-articular platelet-rich plasma can deliver a collection of bioactive molecules, such as autologous growth factors and proteins involved in the quality of tissue repair. Horses (n=5) with osteoarthritis affecting antebrachiocarpal, middle carpal or metacarpophalangeal joints, and horses (n=5) without osteoarthritis of the corresponding joints (radiographically free of osteoarthritis), were used for the production of platelet-rich plasma which was subsequently injected into selected joints. Clinical and ...
van Eps AW, Burns TA.Laminitis is a consequence of primary disease processes elsewhere in the body. The key pathophysiologic events are insulin dysregulation in endocrinopathic laminitis, ischemia in supporting limb laminitis, and inflammation in sepsis-related laminitis. These apparently disparate mechanisms converge to cause lamellar attachment failure through epithelial cell adhesion loss and stretch, possibly mediated by common growth factor signaling pathways. Tissue damage through mechanical distraction, inflammation, pain, and a proliferative epithelial healing response are features of acute laminitis regar...
