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.
McKenna KD, Struble SE, Max LNF, Linardi RL, Ortved KF.To quantify platelets, leukocytes, cytokines, and growth factors in ProVet autologous platelet concentrate (APC). We hypothesized that APC would contain significantly increased leukocytes and platelets compared to whole blood and significantly increased concentrations of anti-inflammatory cytokines and growth factors compared to serum. Unassigned: Blood was obtained from 6 horses and processed to produce APC. Leukocyte and platelet concentrations were quantified in whole blood and APC. Cytokines, including interleukin (IL)-1β, IL-4, IL-6, IL-10, tumor necrosis factor-α, and IL-1Ra, and growt...
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...
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...
Mouncey R, de Mestre AM, Arango-Sabogal JC, Verheyen KL.Gestational and early-life exposures may modulate development during growth and influence future athletic performance. Objective: To investigate associations between gestational and early-life exposures in Thoroughbreds and (i) likelihood of racing, (ii) total number of runs and (iii) total prizemoney by the end of the 3-year-old year. Methods: Prospective cohort. Methods: Daily records were kept on the location and duration of turnout, management and veterinary-attended episodes of disease or injury from birth until leaving the farm or study exit for 129 Thoroughbred foals on six stud farms. ...
Shimizu Y, Sugai-Bannai M, Tanabe H, Saito K, Ito H, Tokushige H, Kamiya K, Hirano-Kodaira M, Yamada M, Leung GN.Somapacitan is the second generation of recombinant human growth hormone (rhGH) medication that retains the pharmacological effects of rhGH but exhibits a longer duration of action due to its reversible albumin-binding in the body. In general, the use of all recombinant growth hormone (rGH) analogues is banned by the human and animal sports regulatory authorities due to their anabolic and lipolytic effects. However, little is known about the elimination kinetics and biological effects of the newly introduced long-acting rhGH, somapacitan, in horses. This paper describes the administration stud...
Carmona JU, López C, Jurado-Grisales C.Platelet-rich plasma (PRP) is widely utilized as a routine treatment for chronic musculoskeletal conditions in horses, such as osteoarthritis, tendinopathies, and desmopathies. This effectiveness stems from the high concentration of growth factors and anti-inflammatory cytokines that are released upon activation of this orthobiologic agent, whether activated endogenously or exogenously. Despite its growing popularity, there is a notable absence of instructional videos that demonstrate the techniques for obtaining PRP in horses. This study examines a double centrifugation tube method for obtain...
Scoggin KE, Adlan F, Fedorka CE, Rakha SI, Stout TAE, Troedsson MHT, Ali HE.The insulin-like growth factor (IGF) system regulates implantation, placental development, and angiogenesis in eutherian mammals. However, little is known about the changes in this system in equine placenta (chorioallantois; CA) and the endometrium (EN) during pregnancy, or the relationship to vascular endothelial growth factor () expression. The current study investigated the expression of the IGF system components, namely the ligands ( and ), their receptors (, , and ), and their binding proteins ( and s) in equine CA at 45 days, 4, 6, 10, and 11 months of gestational age (GA) and immediatel...
Bazvand B, Rashidi A, Zandi MB, Moradi MH, Rostamzadeh J, Mahmoudi P.Iran is home to genetically distinct horse breeds shaped by geography and history. Breeds like the Kurdish, Caspian pony, and Turkmen reflect deep-rooted diversity and unique adaptive traits. Objective: This study aimed to identify genomic regions exhibiting signatures of selection and to detect candidate genes and biological pathways related to body size that may influence performance in various Iranian and exotic horse breeds. Methods: Samples were collected from three Iranian native breeds (Caspian pony, Turkmen, and Kurdish) and three exotic breeds (Fell pony, Arabian, and Akhal-Teke) orig...
Collins E, Barr E, Zhang C, Steadman M, Gilger B, Henriksen ML.To describe the most efficient topical horizontally centrifuged platelet-rich fibrin (H-PRF) treatment protocol for equine ulcerative keratitis (EUK) that is easy to use, and to report the preliminary concentration of growth factors and cytokines in equine H-PRF. Unassigned: 5 client-owned horses diagnosed with EUK were enrolled over an 11-month period. Unassigned: 3 horses were geldings, and 2 were mares. The mean (± SD) age was 5.95 ± 5.01 years. The owners' main goal was to avoid surgery for EUK. Unassigned: H-PRF was used in 3 different protocols: solid H-PRF, sutured to the EUK area (n ...
Ren X, Xue Y, Shen Z, Liu X, Chang X, Meng J, Ren W, Wang J, Yao X, Zeng Y.Branched-chain amino acids (BCAAs) play a crucial role in regulating nutritional metabolism in lactating animals. However, limited research has been conducted on BCAAs in equines. This study aimed to investigate the effects of different doses of BCAA supplementation on plasma and milk amino acid profiles in Yili mares, as well as the growth performance of their suckling foals, thereby providing a scientific basis for optimizing feeding management practices. Eighteen pairs of Yili mares and their sucklings were randomly assigned to four groups: a control group (Group D, no BCAA supplementation)...
Ishimaru M, Kume K, Murase H, Sato F, Matsui A, Ohmura H, Taya K.Thoroughbreds born early in the year are believed to have an advantage in racing. However, the development of endocrine functions in early-born foals in the cold winter climate is unclear. The present study was conducted to elucidate the effect of birth month on the development of endocrine function in Thoroughbred foals born from February to May in Hokkaido by comparing hypothalamic-pituitary axis, adrenal and thyroid functions from birth to 24 weeks of age. Eighty-seven Thoroughbred foals were used to compare the changes in circulating luteinizing hormone (LH), follicle-stimulating hormone (...
Samie KA, Kowalewski MP, Schuler G, Gastal GDA, Bollwein H, Scarlet D.In horses, the mechanisms behind ovarian follicle growth and oocyte maturation remain largely unknown. In other species, oocyte-secreted factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) have been related to the acquisition of developmental competence and to interaction with granulosa cells for the regulation of follicle development. This study assessed the expression and localization of GDF9 in the equine ovary, and its possible relationship with granulosa cell function. Results: Using custom-made antibodies, GDF9 protein was localized in oocytes from th...
Conrad MB, Leatherwood JL, Paris BL, George JM, Martinez RE, Vergara-Hernandez FB, Nielsen BD, Colbath AC, Arnold CE, Glass KG, Welsh TH, Bradbery AN.Extra-label bisphosphonate (BP) use in juvenile horses is anecdotally reported, primarily for analgesic effects, despite the limited scientific understanding of biologic impacts on skeletally immature horses undergoing exercise. The objective of this study was to determine the effects of clodronate disodium (CD), a form of BP, on endocrine regulators of calcium. Thus, 32 yearling Quarter Horses were stratified by age (500 ± 13 d), body weight (BW; 336 ± 26 kg), sex (n = 16 geldings, n = 16 fillies), and initial bone optical density into 1 of 4 treatment groups for a 168-d tr...
Penazzi L, Pagliara E, Nervo T, Ala U, Bertuglia A, Romano G, Hattab J, Tiscar PG, Bergagna S, Pagliasso G, Antoniazzi S, Cavallarin L, Valle E....Foals commonly experience diarrhoea in the first weeks of life. Although this condition is rarely life-threatening, it can have significant health consequences. This study investigated whether new-born foals can benefit from a dietary supplement of nucleotides, as already demonstrated in other species. Dietary nucleotides have positive effects on rapidly proliferating tissues and are considered "semi-essential nutrients" since cells have only a limited capacity to synthesize these compounds. The aim of this study was to investigate whether providing foals with a dietary nucleotide supplementat...
Long S, Maleas G, Belacic ZA, Quam VG, Durgam S.To analyze the cellular, growth factor, and cytokine composition of equine sternal bone marrow aspirate (BMA) and laboratory-centrifuged BMA concentrate (BMAC). Unassigned: This was an in vitro experimental study. Cellular composition, growth factors (IGF-I, VEGF, PDGF, TGF-β1), and cytokines (IL-6, IL-10, tumor necrosis factor-α (TNF-α), and IL-1 receptor antagonist protein [IL-1Ra]) were quantified using a standard automated hematology analyzer and ELISA methods, respectively, in donor-matched BMA, BMAC (in-house centrifugation protocol), whole blood, and platelet-rich plasma (E-PET; Pall...
Li X, Wang Z, Zhu M, Wang B, Teng S, Yan J, Wang H, Yuan P, Cao S, Qu X, Wang Z, Zhan K, Choudhury MP, Yang X, Bao Q, He S, Liu L, Zhao P, Jiang J....Horse domestication revolutionizes human civilization by transforming transportation, agriculture, and warfare patterns. Despite extensive studies on modern domestic horse origins, the intricate demographic history and genetic signatures underlying pony size remain unexplored. Here, a high-quality genome assembly of the Chinese Debao pony is presented, and 452 qualified individuals from 64 horse breeds worldwide are extensively analyzed. The authors' results reveal the conservation of ancient components in East Asian horses and close relationships between Asian horses and Western pony lineages...
Son JK, De Paz P, Kim J, Sanaei R, Ryu S, Bailey S, Davies HMS.Changes in the third metacarpal (MC3) mid-diaphyseal dimensions were measured radiographically in young Thoroughbred racehorses through race training and found to be associated with a higher risk of shin soreness. However, it is still unclear whether such negative MC3 morphologies are set congenitally or through development. Objective: To quantify MC3 bone dimensional changes through growth. Methods: Longitudinal. Methods: Twenty privately owned Thoroughbred foals were radiographed bimonthly from birth to 14 months of age. Four linear MC3 parameters (proximodistal MC3 length, mid-diaphyseal do...
Beaumont RE, Smith EJ, David C, Paterson YZ, Faull E, Guest DJ.Tendon injuries are a common problem in humans and horses. There is a high re-injury rate in both species due to the poor regeneration of adult tendon and the resulting formation of scar tissue. In contrast, fetal tendon injuries undergo scarless regeneration, but the mechanisms which underpin this are poorly defined. It is also unclear if tendon cells derived from embryonic stem cells (ESCs) would aid tendon regeneration. In this study we determined the responses of adult, fetal and ESC-derived equine tenocytes to a range of cytokines, chemokines and growth factors that are upregulated follow...
Barot D, Usimaki A, Linardi RL, Arensberg CM, Ortved KF.Quantify the concentration of α2-macroglobulin (A2M), immunomodulatory cytokines, and TGF-β1 factors in 4 commercially available autologous blood-based products including conditioned A2M (CA2M; Alpha2EQ; Astaria Global), autologous protein solution (APS; Pro-Stride; Zoetis), platelet-rich plasma (PRP; Restigen; Zoetis), and autologous conditioned plasma (ACP; Arthrex ACP). We hypothesized that CA2M would have higher concentrations of A2M and lower concentrations of cytokines and growth factors compared to APS, PRP, and ACP. Unassigned: Blood was obtained from 6 healthy, adult horses and proc...
Chatha MA, Ahmad N, Abbas MA, Saadullah M, Khan JA.This study was designed to explore the impact of intrinsic (breed of foal, age of dam, and age of foal at weaning) and extrinsic (season of birth and housing type) factors on the growth and survival of foals in the subtropical conditions of Pakistan. For the growth study, retrospective data analysis of foals (n = 150) born from purebred brood mares of Thoroughbred, Arabs, and Percheron breeds (n1, n2, and n3 = 50 each) was made. Six hundred and twenty-four (n = 624) foals born between 2020 to 2022 were observed for the study of foal survival rate. The survival of these foals till the age of on...
Gallacher K, Champion K, Denholm KS.Foals suffer from total failure to transfer passive immunity (TFTPI) when serum immunoglobulin (IgG) is <4 g/L, and partial failure to transfer passive immunity (PFTPI) when serum IgG is 4-8 g/L. Objective: To explore risk factors for poor serum IgG concentration. Methods: Retrospective observational study. Methods: Data from 535 Thoroughbred foals born to 177 mares were analysed and included foal sex, birthweight, month and year of birth and colostrum Brix %. Associations between dam age and colostrum Brix (%); and between foal serum IgG and liveweight gains were also measured. Pre-suckle...
Egli P, Boone L, Huber L, Higgins C, Gaonkar PP, Arrington J, Naskou MC, Peroni J, Gordon J, Lascola KM.Platelet lysate (PL) demonstrates antimicrobial and anti-inflammatory properties offering potential for treatment of bacterial pneumonia in horses. It remains unknown whether nebulization is suitable for PL administration in horses. This pilot study characterized particle size and flow rate of pooled equine PL (single preparation) nebulized using an equine-specific nebulizer (Flexivent®). Unassigned: Protein composition and antimicrobial activity were compared before and after nebulization. Protein composition was evaluated according to growth factor, antimicrobial peptide and cytokine concen...
Souza LA, Hunka MM, Rezende Júnior SF, Silva CJFLD, Manso HECDCC, Simões J, Coelho CS, Fazio F, Aragona F, Manso Filho HC.The aim of this two-phase study was to evaluate the use of beet pulp concentrate (BPC) in athletic horses. On the first trial the effects of supplementation with 820g of BPC for 12 weeks were assessed and a crossover postprandial curves of blood biomarkers were determined in five adult Arabian mares. Differences were found in T-chol, HDL-chol, TPP and MCHC (p < 0.05). Postprandial curves varied among challenges (p < 0.05) for glucose, insulin, and hematocrit. These results confirmed that BPC supplementation led to changes in blood biomarkers, without inducing major metabolic disruption. Th...
Van Mol B, Oosterlinck M, Janssens S, Buys N, Pille F.Various environmental and genetic risk factors are linked to the pathogenesis of equine osteochondrosis and osteochondral fragments in the fetlock joint. Therefore, a scoping review was conducted to describe current evidence linking genetic factors and environmental factors of these osteochondral disorders. This article constitutes the first part of this scoping review and focuses on environmental factors, with the second part addressing genetic factors. To identify potentially relevant papers online bibliographical databases PubMed and Web of Science were utilised, supplemented with articles ...
Rudnick MJ, Stewart HL, Burleson MD, Levine DG.Slow hoof growth poses a clinical challenge when hoof wear exceeds natural growth. Many treatment options have been reported without controlled prospective trials. The objective of this study was to evaluate the effect of transdermal CO2 on the rate of growth in treated hooves. Methods: A prospective, randomized, blinded, crossover study of 14 Warmblood mares. Horses were randomly assigned a number and allocated for treatment of the front feet with room air or CO2 for 30 minutes 3 times per week, and groups were switched after 5 weeks. Hoof growth was measured on the dorsal midline and the qua...
Wang X, Shi M, Cao C, Zeng R, Yao Y.Lactobacillus casei Zhang (Lac.z), isolated from traditional sour horse milk in Inner Mongolia, can alleviate various diseases and promote health. Our previous studies found that pretreatment with live Lac.z (L-Lac.z) could significantly attenuate acute kidney injury and delay the progression of chronic renal fibrosis. However, it is unknown whether these effects could be maintained by pasteurized Lac.z (P-Lac.z). Mouse models of acute kidney injury and chronic renal fibrosis induced by renal bilateral ischemia-reperfusion (BIR) surgery were treated with L-Lac.z or P-Lac.z by gavage. Serum and...
Yaneselli K, Ávila G, Rossi A, Rial A, Castro S, Estradé MJ, Suárez G, Algorta A.Platelet lysate (PL) is investigated as a potential replacement for fetal bovine serum (FBS) in cell culture. However, there is limited research on its impact on the immune profile of equine mesenchymal stromal cells (eMSCs). This study aimed to evaluate the effects of different PL formulations on the proliferative capacity, multipotentiality, and immune profile of equine adipose tissue-derived MSCs (eAD-MSCs). growth kinetics and trilineage differentiation of eAD-MSCs ( = 7) were assessed under three culture conditions: medium-concentration PL (MPL), high-concentration PL (HPL), and FBS ...
Chiara M, Mariaelena C, Alessandro C, Davide B, Lavinia C, Paola MM, Barbara L, Chiara DP, Flagiello F, Pia PM.The advanced-PRF+ (A-PRF+) is a platelet concentrate, showing a higher concentration of growth factors, an increased number of cells and looser structure of the fibrin clot than leukocyte-PRF. A high variability in the size of PRF associated with patients, haematological features and centrifugation protocols was reported. The aims of this study were to evaluate the feasibility of A-PRF+ production in the field and the correlation between haematological parameters, macroscopic and microscopic features in equine A-PRF+. Samples from twenty Standardbred horses (3-7 years) were harvested with gla...
Son JK, De Paz P, Kim J, Sanaei R, Seungho R, Bailey S, Davies HMS.The risk of carpal injury in racehorses may be related to the morphology, yet whether carpal morphologies are set from birth or change through growth remains unclear. Objective: To quantify carpal bone changes through growth. Methods: Twenty privately owned Thoroughbred foals born between January 2022 and May 2023 were radiographed bimonthly from birth to 10 months of age. Imprint training was used to take radiographs safely without chemical restraints. Fifteen individual and 11 relative angular carpal parameters were measured using ImageJ on dorsopalmar radiographs of the carpus at zero degre...
Fortier LA, Mohammed HO, Lust G, Nixon AJ.Composites of chondrocytes and polymerised fibrin were supplemented with insulin-like growth factor-I (IGF-I) during the arthroscopic repair of full-thickness cartilage defects in a model of extensive loss of cartilage in horses. Repairs facilitated with IGF-I and chondrocyte-fibrin composites, or control defects treated with chondrocyte-fibrin composites alone, were compared before death by the clinical appearance and repeated analysis of synovial fluid, and at termination eight months after surgery by tissue morphology, collagen typing, and biochemical assays. The structure of cartilage was ...
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...
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...
Ytrehus B, Carlson CS, Ekman S.Osteochondrosis is a common and clinically important joint disorder that occurs in human beings and in multiple animal species, most commonly pigs, horses, and dogs. This disorder is defined as a focal disturbance of enchondral ossification and is regarded as having a multifactorial etiology, with no single factor accounting for all aspects of the disease. The most commonly cited etiologic factors are heredity, rapid growth, anatomic conformation, trauma, and dietary imbalances; however, only heredity and anatomic conformation are well supported by the scientific literature. The way in which t...
Schnabel LV, Lynch ME, van der Meulen MC, Yeager AE, Kornatowski MA, Nixon AJ.Tendinitis remains a catastrophic injury among athletes. Mesenchymal stem cells (MSCs) have recently been investigated for use in the treatment of tendinitis. Previous work has demonstrated the value of insulin-like growth factor-I (IGF-I) to stimulate cellular proliferation and tendon fiber deposition in the core lesion of tendinitis. This study examined the effects of MSCs, as well as IGF-I gene-enhanced MSCs (AdIGF-MSCs) on tendon healing in vivo. Collagenase-induced bilateral tendinitis lesions were created in equine flexor digitorum superficialis tendons (SDFT). Tendons were treated with ...
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...
Goodrich LR, Hidaka C, Robbins PD, Evans CH, Nixon AJ.Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model. A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 x 10(7) AdIGF-1 modified chondrocytes and the contralateral...
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...
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 ...
Dowling BA, Dart AJ, Hodgson DR, Smith RK.The superficial digital flexor tendon (SDFT) is an elastic structure that during maximal exercise appears to operate close to its functional limits. The biomechanical and biochemical responses to exercise, injury, and healing are still poorly understood but ongoing research is providing valuable new information which is addressed in this review. It appears that the SDFT matures early, after which time it has limited ability to adapt to stress and undergoes progressive degeneration. Focal hypocellularity, collagen fibril degeneration, selective fibril loading and alterations in the noncollageno...
Marędziak M, Marycz K, Lewandowski D, Siudzińska A, Śmieszek A.The aim of this work study was to evaluate the cytophysiological activity of equine adipose-derived stem cells (ASCs) cultured under conditions of static magnetic field. Investigated cells were exposed to a static magnetic field (MF) with the intensity of 0.5 T. In order to investigate the effects of magnetic field on stem cell signaling, the localization and density and content of microvesicles (MVs) as well as morphology, ultrastructure, and proliferation rate of equine ASCs were evaluated. Results showed that potential of equine adipose-derived mesenchymal stem cells was accelerated when ma...
Bussche L, Van de Walle GR.Mesenchymal stromal cells (MSCs) have received much attention as a potential treatment of ischemic diseases, including ischemic tissue injury and cardiac failure. The beneficial effects of MSCs are thought to be mediated by their ability to provide proangiogenic factors, creating a favorable microenvironment that results in neovascularization and tissue regeneration. To study this in more detail and to explore the potential of the horse as a valuable translational model, the objectives of the present study were to examine the presence of angiogenic stimulating factors in the conditioned medium...
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 ...
Bosch G, Moleman M, Barneveld A, van Weeren PR, van Schie HT.The repair process of tendon injuries, which are common in both human and equine athletes, is slow and the quality of the repair tissue is often inferior to the original tendon tissue, which frequently leads to re-injury. The relatively poor vascularization of tendons is considered to be one of the reasons for their limited healing potential. Recently, platelet-rich plasma (PRP), an autologous concentrate of platelets, rich in growth factors, has been shown to enhance the repair process of injured tendons. This effect has been ascribed to the high levels of growth factors in PRP, several of wh...
Bertone AL, Ishihara A, Zekas LJ, Wellman ML, Lewis KB, Schwarze RA, Barnaba AR, Schmall ML, Kanter PM, Genovese RL.To evaluate intra-articular autologous protein solution (APS) for the treatment of osteoarthritis in horses. Animals-40 client-owned horses with naturally occuring osteoarthritis. Methods: APS was generated from a dual-device system that concentrated plasma and WBC proteins and enriched platelet growth factors. Horses were randomly assigned to receive an intra-articular injection of 5 mL of saline (0.9% NaCl) solution (n = 20) or APS (20), exercised on a treadmill, and evaluated on the basis of lameness grades, kinetic gait analysis, joint circumference, and range of motion for 14 days. Horses...
Caliari SR, Harley BA.Biomolecular environments encountered in vivo are complex and dynamic, with combinations of biomolecules presented in both freely diffusible (liquid-phase) and sequestered (bound to the extracellular matrix) states. Strategies for integrating multiple biomolecular signals into a biomimetic scaffold provide a platform to simultaneously control multiple cell activities, such as motility, proliferation, phenotype, and regenerative potential. Here we describe an investigation elucidating the influence of the dose and mode of presentation (soluble, sequestered) of five biomolecules (stromal cell-de...
Textor JA, Tablin F.To investigate and compare clinically relevant Platelet-rich plasma (PRP) activation methods. Methods: Experimental. Methods: PRP was prepared from 6 equine subjects. Activation of the PRP was performed by 4 methods (autologous thrombin, bovine thrombin, calcium chloride (CaCl(2) ), or freeze-thaw). The resultant PDGF-BB (where PDGF is platelet-derived growth factor) and TGFβ1 (where TGFβ is transforming growth factor beta) levels in PRP releasates were quantified by Enzyme-linked immunosorbent assay (ELISA) and compared. Growth factor contents were also compared between platelet-rich clots ...
Morisset S, Frisbie DD, Robbins PD, Nixon AJ, McIlwraith CW.Repair of cartilage defects involves sequential participation of specific hormones and growth factors with potential impairment by inflammatory cytokines. We explored an in vivo gene therapy treatment to supply adenoviral vectors carrying the genes of interleukin-1 receptor antagonist protein (IL-1ra) and insulinlike growth factor-1 (IGF-1), hoping to enhance repair of full-thickness equine chondral defects treated with microfracture. We asked whether our treatment could (1) increase proteoglycan and Type II collagen content in the repair tissue, (2) improve the macroscopic and histomorphometr...
Giraldo CE, López C, Álvarez ME, Samudio IJ, Prades M, Carmona JU.There is no information on the effects of the breed, gender and age on the cellular content and growth factor (GF) release from equine pure-platelet rich plasma (P-PRP) and pure-platelet rich gel (P-PRG). The objectives of this study were: 1) to compare the cellular composition of P-PRP with whole blood and platelet poor plasma (PPP); 2) to compare the concentration of transforming GF beta 1 (TGF-β1) and platelet derived GF isoform BB (PDGF-BB) between P-PRP treated with non-ionic detergent (P-PRP+NID), P-PRG (activated with calcium gluconate -CG-), PPP+NID, PPP gel (PPG), and plasma and; 3) ...
Garbin LC, Olver CS.Autologous platelet-rich plasma (PRP) is a biological preparation made from the patient's own plasma that contains a platelet concentration above the whole blood baseline. Owing to the release of growth factors and other cytokines after degranulation, platelets have a central role in inflammation and in different stages of the healing process. For this reason, PRP-derived products have been used to enhance healing of musculoskeletal injuries and modulate progression of inflammatory processes, including osteoarthritis (OA). Osteoarthritis is one of the main causes of musculoskeletal disabilitie...
Haupt JL, Frisbie DD, McIlwraith CW, Robbins PD, Ghivizzani S, Evans CH, Nixon AJ.This study evaluated the potential of gene induced synoviocyte expression of a combination of insulin-like growth factor-I (AdIGF-I) and interleukin-1 receptor antagonist protein (AdIL-1Ra) to control articular cartilage degradation in vitro. Cartilage explants and synovial membrane were harvested from young mature horses. Synovial monolayers were established and either (1) maintained as untransduced controls; (2) transduced with AdIGF-I at 200 MOI in 500 microl serum-free medium; (3) transduced with AdIL-1Ra at 100 MOI; or (4) transduced with a combination of AdIGF-I (200 MOI) and AdIL-1Ra (1...
Barsby T, Bavin EP, Guest DJ.The natural reparative mechanisms triggered by tendon damage often lead to the formation of biomechanically inferior scar tissue that is prone to re-injury. Before the efficient application of stem cell-based regenerative therapies, the processes regulating tenocyte differentiation should first be better understood. Three-dimensional (3D) growth environments under strain and the exogenous addition of transforming growth factor beta3 (TGF-β3) have separately been shown to promote tendon differentiation. The aim of this study was to determine the ability of both of these factors to induce tendo...
Hortensius RA, Harley BA.The design of biomaterials for regenerative medicine can require biomolecular cues such as growth factors to induce a desired cell activity. Signal molecules are often incorporated into the biomaterial in either freely-diffusible or covalently-bound forms. However, biomolecular environments in vivo are often complex and dynamic. Notably, glycosaminoglycans (GAGs), linear polysaccharides found in the extracellular matrix, are involved in transient sequestration of growth factors via charge interactions. Biomaterials mimicking this phenomenon may offer the potential to amplify local biomolecular...
Stewart AA, Byron CR, Pondenis H, Stewart MC.To determine whether fibroblast growth factor-2 (FGF-2) treatment of equine mesenchymal stem cells (MSCs) during monolayer expansion enhances subsequent chondrogenesis in a 3-dimensional culture system. Methods: 6 healthy horses, 6 months to 5 years of age. Methods: Bone marrow-derived MSCs were obtained from 6 horses. First-passage MSCs were seeded as monolayers at 10,000 cells/cm(2) and in medium containing 0, 1, 10, or 100 ng of FGF-2/mL. After 6 days, MSCs were transferred to pellet cultures (200,000 cells/pellet) and maintained in chondrogenic medium. Pellets were collected after 15 days....
Haber M, Cao Z, Panjwani N, Bedenice D, Li WW, Provost PJ.The physiologic mechanisms involving growth factors, including PDGF-BB, EGF, and TGF-beta 1, as potent mediators of fibroblasts and epithelial cells in corneal wound healing remain unknown. The goal of this study was to determine culture methods for equine epithelial cells and keratocytes and to investigate how exogenous growth factors influence proliferation of both cell types. Methods: Cell cultures were established from healthy corneas harvested from horses immediately following euthanasia and maintained using standard tissue culture protocols. To determine the effects of PDGF-BB, EGF, TGF-...
Saito S, Ugai H, Sawai K, Yamamoto Y, Minamihashi A, Kurosaka K, Kobayashi Y, Murata T, Obata Y, Yokoyama K.Embryonic stem (ES) cells are pluripotent cells with the potential capacity to generate any type of cell. We describe here the isolation of pluripotent ES-like cells from equine blastocysts that have been frozen and thawed. Our two lines of ES-like cells (E-1 and E-2) appear to maintain a normal diploid karyotype indefinitely in culture in vitro and to express markers that are characteristic of ES cells from mice, namely, alkaline phosphatase, stage-specific embryonic antigen-1, STAT-3 and Oct 4. After culture of equine ES-like cells in vitro for more than 17 passages, some ES-like cells diffe...
Brommer H, Brama PA, Laasanen MS, Helminen HJ, van Weeren PR, Jurvelin JS.The concept of functional adapatation of articular cartilage during maturation has emerged from earlier biochemical research. However, articular cartilage has principally a biomechanical function governed by joint loading. Objective: To verify whether the concept of functional adaptation can be confirmed by direct measurement of biomechanical properties of cartilage. Objective: Fetuses have homogeneous (i.e. site-independent) cartilage with regard to biomechanical properties. During growth and development to maturity, the biomechanical characteristics adapt according to functional (loading) de...
Worster AA, Nixon AJ, Brower-Toland BD, Williams J.To determine the morphologic and phenotypic effects of transforming growth factor beta1 (TGFbeta1) on cultured equine mesenchymal stem cells (MSC) and articular chondrocytes. Methods: Bone marrow aspirates and articular cartilage samples from a 2-year-old and two 8-month-old horses. Methods: After initial isolation and culture, MSC and chondrocytes were cultured in Ham's F-12 medium supplemented with TGF-beta1 at a concentration of 0, 1, 5, or 10 ng/ml. Medium was exchanged on day 2, and cells were harvested on day 4. Medium was assayed for proteoglycan (PG) content. Total RNA was isolated fro...
Fortier LA, Smith RK.After tendon injury, the scar tissue that replaces the damaged tendon results in a substantial risk for reinjury. The goal of regenerative therapies is to restore normal structural architecture and biomechanical function to an injured tissue. Successful restoration processes for any tissue are thought to recapitulate those of development, in which there are spatial and temporal interactions between scaffold, growth factors, and cell populations.
Raabe O, Shell K, Fietz D, Freitag C, Ohrndorf A, Christ HJ, Wenisch S, Arnhold S.Mesenchymal stem cells have become extremely interesting for regenerative medicine and tissue engineering in the horse. Stem cell therapy has been proven to be a powerful and successful instrument, in particular for the healing of tendon lesions. We pre-differentiated equine adipose-tissue-derived stem cells (ASCs) in a collagen I gel scaffold by applying tensile strain, growth differentiation factors (GDFs) and various oxygen tensions in order to determine the optimal conditions for in vitro differentiation toward the tenogenic lineage. We compared the influence of 3% versus 21% oxygen tensio...
