Bone marrow in horses is a spongy tissue found within the cavities of certain bones, such as the pelvis, ribs, and femur. It is a vital component of the hematopoietic system, responsible for the production of blood cells, including red blood cells, white blood cells, and platelets. These cells are crucial for oxygen transport, immune function, and blood clotting, respectively. Bone marrow consists of two types: red marrow, which is actively involved in blood cell production, and yellow marrow, which primarily stores fat. The composition and activity of bone marrow can change with age, health status, and physiological demands. This page compiles peer-reviewed research studies and scholarly articles that explore the structure, function, and clinical implications of bone marrow in equine health and disease.
Skierbiszewska K, Turek B, Jasiński T, Kaczorowski M, Kozłowska N, Higuchi J, Domino M.Bone grafting in equine medicine offers a promising contribution to treating orthopaedic developmental diseases and chondral, osteochondral and segmental bone defects. Among grafts, synthetic bone substitutes-alloplastics-show favourable biological properties addressing numerous limitations presented by autografts, xenografts and allografts. Objective: To compile and disseminate clinical data and research findings from existing publications on the use of alloplastics in horses. Methods: Systematic review. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-analysis 202...
Mazzucco L, Marcatili M, Withers J, Cantatore F.Superficial digital flexor tendinopathy is a common cause of forelimb lameness in Thoroughbred racehorses and sports horses; however, this condition is rarely observed in the hindlimb. A 16-year-old Irish sports horse gelding was presented with bilateral swelling in the plantar metatarsal region and severe bilateral hindlimb lameness visible at the walk. The lameness occurred after the cross-country phase of an eventing competition. The clinical suspicion of superficial digital flexor tendon (SDFT) injury was confirmed after ultrasonographic examination, which revealed an extensive core lesion...
Kamr A, Fortin-Trahan R, Arroyo LG, Hostnik LD, Gomez DE, Toribio RE.Hypocalcemia is frequent in horses with colitis. Information on serum parathyroid hormone (PTH) concentrations and its association with bone turnover biomarkers in horses with colitis is lacking. We aimed to determine the association between serum bone resorption biomarkers (C-terminal telopeptide of type I collagen [CTX-I]) and bone formation (osteocalcin [OCN]) with blood PTH, total calcium (tCa), ionized calcium (iCa), phosphorus (Pi), and total magnesium (tMg) concentrations, and mortality in horses with acute colitis. A total of 163 horses were divided into colitis (n = 127) and healt...
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...
Salinas P, Vergara MA, Tapia D.Navicular syndrome (NS) is a chronic, degenerative condition of the equine thoracic limb that compromises the distal sesamoid bone (DSB) and associated structures responsible for stabilization and load absorption during locomotion. Although historically attributed to vascular alterations, its etiology is now recognized as biomechanical, characterized by chronic overload of the deep digital flexor tendon. Conventional diagnostic techniques-radiography, scintigraphy, and ultrasonography-lack the sensitivity and precision required to detect early microarchitectural alterations. This study aimed t...
De Zani D, Rabbogliatti V, Rabba S, Auletta L, Longo M, Zani DD.Damage to the osteochondral unit is a common cause of lameness in horses. Published descriptions of MRI findings of osteochondral unit and subchondral damage are currently lacking, and only a few reports describe outcomes in sport horses. The aims of this case series retrospective study were to describe different MRI patterns of osteochondral/subchondral pathology in the fetlock joint using low-field MRI and to provide outcome information. A total of 35 sport horses were included. Data regarding detailed clinical history, treatment and outcome were evaluated. MRI identified a total of 39 bone ...
Chapple AR, Daglish J, Stover SM, Slipchenko N, Phillips KL.Stress fracture is an important cause of mortality and morbidity in racing Thoroughbreds. Nuclear scintigraphy is the imaging modality of choice for investigating unlocalised stress-related bone remodelling in horses. Stress fractures of the caudal lumbar vertebral column have been previously described in both racing Quarter horses and racing Thoroughbreds post-mortem. There is a lack of literature describing the imaging appearance of vertebral stress fractures in racehorses ante-mortem. Objective: To describe: (1) ante-mortem scintigraphic appearance of presumed thoracolumbar vertebral stress...
Morrice-West AV, Wong ASM, Hitchens PL, Whitton RC.Musculoskeletal injuries (MSI) in racehorses are not typically spontaneous events, but develop gradually through cumulative cycles of loading over time. Stride characteristics can now be recorded with wearable technology, providing opportunity to quantify the skeletal impact of galloping over time. We estimated bone fatigue accumulation based on speed (m/s) and number of strides from n = 3168 race starts by n = 405 Thoroughbreds commencing racing in Tasmania, Australia between 2011 and 2016. The percentage bone fatigue accumulated was divided by various time periods (career, active car...
Micheau L, Audigié F, Moiroud C, Jacquet S.Disuse-induced bone loss during stall confinement and immobilization is a major concern in horses because it impairs recovery and increases susceptibility to further injury. Experimental models are needed to evaluate therapeutic options, but most available equine models rely on cast immobilization, which is technically demanding and may be associated with complications. This study aimed to assess a simpler and less restrictive model to induce a quantifiable decrease in bone density in horses. Six French Standardbred horses underwent eight weeks of stall confinement, with a wooden wedge fitted ...
DI Stefano DA, Coccoluto L, Panina-Bordignon P, Brambilla E, Ruffini F, Murtaj V, Orlando F, Colombo M, Frigerio C, DI Bona A, Recupero D, Morroni M....Bone grafting is a surgical procedure that involves the use of bone tissue or bone substitutes to repair damaged bone. In dentistry and maxillofacial surgery, bone graft substitutes from various sources are commonly used. Given their critical role in clinical outcomes, it is essential to thoroughly investigate the biological and mechanical properties of these materials. Methods: In this in vitro study, we evaluated the biological properties of two equine-derived bone graft substitutes in comparison to β-tricalcium phosphate. The materials included one equine-derived graft containing hydrolyze...
Micheau L, Jacquet-Guibon S, Tallaj A, Bertoni L, Denoix JM, Coudry V.To describe the type and distribution of carpal joint lesions causing lameness in show jumping horses and describe their 1-year performance outcomes. Unassigned: 15 show jumping horses (median age, 9 years; IQR, 8 to 11 years) of 3 different breeds, mostly Selle Français, evaluated at a referral center between 2013 and 2023. The inclusion criterion was forelimb lameness localized to the carpus, confirmed by perineural or IA analgesia and/or increased radiopharmaceutical uptake on scintigraphy. Horses with limb conformation abnormalities, a history of trauma, or extra-articular soft tissue les...
Marcatili M, Kalinovskiy A, Christoph L.To describe the additional information provided by computed tomography (CT) in planning and assisting repair of comminuted fractures of the middle phalanx (MP) in Warmblood horses. Methods: Case series. Methods: Six adult Warmblood horses. Methods: The case records of horses undergoing CT examination prior to internal fixation of comminuted MP fractures were reviewed. All horses underwent radiographic and preoperative CT examination. A standardized fast protocol (SFP) to assess CT images was used. Surgical repair consisted of fracture repair and proximal interphalangeal joint arthrodesis using...
Pan M, Malekipour F, Pivonka P, Morrice-West AV, Flegg JA, Whitton RC, Hitchens PL.Fractures of the distal limb in Thoroughbred racehorses primarily occur because of accumulation of bone microdamage from high-intensity training. Mathematical models of subchondral bone adaptation of the third metacarpal lateral condyles are capable of approximating existing data for Thoroughbred racehorses in training or at rest. To improve upon previous models, we added a dynamic resorption rate and microdamage accumulation and repair processes. Our ordinary differential equation model simulates the coupled processes of bone adaptation and microdamage accumulation, and is calibrated to data ...
de Oliveira Ferreira LV, Maia L, Barberini DJ, Takahira RK, de Vasconcelos Machado VM, Machado GF, de Melo GD, Amorim RM.Mesenchymal stem cells (MSCs) have emerged as a promising alternative for treating neurological disorders due to their neuroprotective, neuroregenerative, immunomodulatory, anti-inflammatory, and anti-apoptotic properties. The use of allogeneic MSCs offers advantages such as the selection of specific cells and their immediate availability. This study aimed to evaluate the safety and feasibility of intrathecal transplantation of allogeneic equine bone marrow-derived MSCs (EqBM-MSCs) in healthy horses. Ten healthy horses (five-12 years old) were randomly divided into two groups. In the control g...
Larson MK, Gaffney C, Hoagland C, Jayawickrama J, Kamm JL.To determine the xenogen-free serum source that provides the greatest number of live equine mesenchymal stromal cells (MSCs) while maintaining the MSC phenotype. Unassigned: Equine bone marrow-derived MSCs from 8 horses were cultured for 7 days in media containing one of the following serum treatments: 10% xenogeneic serum, 10% or 20% commercial allogeneic equine serum, 10% autologous serum, 10% equine pooled platelet lysate (PPL), or a staged media reduction of xenogeneic media. Live cell numbers, MSC viability, and MSC immunophenotype were compared. Unassigned: The use of 10% commercial allo...
Kelley JL, Rawlinson JE, Bell CM.Cystic and pseudocystic masses of the equine maxilla and mandible are rare lesions that result in clinically significant morbidity and/or mortality for the patient. Previous literature consists of case reports or case series. Few studies have addressed the variety of cystic lesions and comparative features. The aim of this study was to retrospectively describe the clinical signs, imaging findings, histopathologic diagnoses, treatments, and clinical outcomes for cystic masses in the equine maxilla and mandible. Unassigned: Cases were recruited from six sources including a pathology laboratory, ...
Zhang Z, Li J, Mai Z, Yang Y, Fu H, Cao X, Li T, Guo Q, Ma Y.The incidence of sports injuries in horses is increasing, thus accurate assessment, diagnosis, and treatment are critical. Among common sports-related injuries, proximal sesamoid bone fractures (PSBFs) are one of the most frequent types. To investigate the effects of low-intensity pulsed ultrasound (LIPUS) on imaging and hematological parameters of PSBFs, providing a clinical reference for the diagnosis and treatment of PSBFs in racehorses. After clinical diagnosis and radiographic examination confirmed the disease and its location, the affected horses were randomly divided into two groups: th...
Myers TJ, Sampson SN, Glass KP, Russell LA.Central tarsal bone (CTB) fractures are challenging to diagnose, and cross-sectional imaging is required for definitive characterization and surgical planning. This retrospective case series aims to provide the first description of high-field (3-T) MRI characteristics of CTB fractures, concurrent pathology, and clinical presentation in 8 performance horses. Unassigned: 8 horses (9 limbs) diagnosed with a CTB fracture on high-field MRI at one tertiary referral hospital between 2013 and 2023 were identified via electronic medical records search. Unassigned: Quarter Horses (6 of 8) used for Weste...
Martins ALM, Estevam LGTM, Freire MA, Lima ACVMDR, de Oliveira FCB, Dutra-Rêgo F, Carvalho GML, Ribeiro VM, Paz GF.Equine leishmaniasis is a widespread disease in Brazil, mainly caused by Leishmania (Viannia) braziliensis, with occasional cases involving Leishmania (Leishmania) infantum. This study reports a mixed infection in a 6-year-old mare from rural Itabirito, Minas Gerais, Brazil. The mare exhibited nodular cutaneous lesions on all limbs but had no other health issues. Skin and bone marrow samples were collected and analyzed using parasitological and molecular methods targeting the hsp70 gene and ITS1 region. Both L. (V.) braziliensis and L. (L.) infantum were identified, confirming a mixed infectio...
Germonpré J, Lorenz I, Vandekerckhove LMJ, Duchateau L, Diekhoff T, Vanderperren K.Dual-energy computed tomography (DECT) is a promising advancement for detecting bone edema-like lesions (BME). However, its application in horses remains limited. The aim of this study was to evaluate DECT virtual-non-calcium (VNCa) imaging in the equine foot and establish which confounding factors could influence its applicability in clinical practice. The DECT VNCa map of 14 standing and 5 cadaveric (recumbent) cases with foot-related lameness was scored in consensus by two readers in comparison to MRI. Overall, 17/19 cases demonstrated BME on MRI, whereas 2 did not. Agreement between DECT V...
Chaipokam J, Rojnuckarin P.In Thailand, stem cell transplantation and horse antithymocyte globulin (ATG) are not accessible for most adult aplastic anemia (AA) patients. Alternative therapies are required. We conducted a cohort study of 110 adult AA patients treated with oxymetholone alone for at least 30 days from 2013 to 2023. Response at month 6 and prognostic factors were evaluated. The mean age was 63.4 years old and 58.2% were female. Severe and very severe AA (SAA/VSAA) comprised 64.5% and 3.6%, respectively. The initial oxymetholone daily dose was 150 mg in 66.4%. The overall response was 56.4% (50.7% for SAA/V...
Contentin R, Jehl C, Commenchail K, Legendre F, Galéra P, Cassé F, Demoor M.Osteoarthritis (OA) affects millions of people globally, causing irreversible cartilage damage, chronic inflammation, and progressive joint dysfunction. Similarly, horses can develop OA spontaneously or due to their athletic careers, influenced by mechanical and biochemical factors. Current treatments primarily focus on symptom relief without promoting cartilage regeneration. In line with the 3Rs principles (refine, reduce, replace), the development of OA models is essential for advancing new therapeutic approaches against OA. In response to this need, the present study aimed to develop an m...
Maguire M, Brusie R.To determine the outcome of skeletally mature performance horses with subchondral bone cysts and fissures in the proximal aspect of the first phalanx treated by lag screw compression. Unassigned: Case records of horses that underwent lag screw compression to treat subchondral bone lesions in the proximal aspect of the first phalanx were reviewed. Performance horses > 5 years old with lameness referrable to the fetlock region; radiographic or other advanced imaging evidence of subchondral bone lesions, with no other concurrent cause for lameness; and at least 6 months of follow-up data were inc...
Lee S, Kyaw MT, Harada K, Kusakabe KT, Igase M, Sasaki N.Generally, most mesenchymal stem cells (MSCs) have lower pluripotency and limited differentiation potential than embryonic stem cells (ESCs). However, a small subpopulation of MSCs, called multilineage differentiating stress-enduring (MUSE) cells, exhibit pluripotency. MUSE cells express stage-specific embryonic antigen 3 (SSEA-3), a sphingoglycolipid. Here, we isolated and investigated the pluripotency of SSEA-3-positive MSCs (MUSE cells). Six thoroughbred horses were used as test subjects. MSCs were harvested from the bone marrow of the thoracic vertebrae under ultrasound guidance. Harvested...
Euppayo T, Siengdee P, Limlenglert P, Nganvongpanit K, Watanabe G, Kasashima Y, Arai K.The self-renewal capacity of chondrocytes in osteoarthritis (OA) joints is limited, and mesenchymal stem cells (MSCs) are crucial in disease treatment. This study established an OA model from equine bone marrow-derived mesenchymal stem cells (eBMSCs). The eBMSCs were cultured and differentiated into chondrocytes to generate cartilage pellets, which were induced for 7 d with inflammatory cytokines, interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) to mimic OA conditions. Treated culture medium was collected to estimate enzyme activity (MMP-2, MMP-3, and MMP-9) using zymograph...
Nagy A, Dyson SJ.There is no description of comparative magnetic resonance imaging (MRI) and fan-beam computed tomography (CT) findings in the fetlock of lame sports horses. Objective: To document low-field MRI and fan-beam CT diagnoses in the lame and nonlame limbs of sports horses with fetlock region pain, and to evaluate whether combined imaging provides superior information to either technique alone. Methods: Retrospective descriptive study. Methods: Clinical records of sports horses with pain causing lameness localised to the metacarpo/metatarsophalangeal joint region that had undergone fan-beam CT and lo...
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...
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...
Beck C, Hitchens PL, Whitton RC.Post-mortem studies have shown that fractures involving the metacarpophalangeal/metatarsophalangeal or fetlock joint are associated with focal areas of microdamage. Identification of computed tomography (CT) features consistent with microdamage and their association with fracture may aid in identification of horses at risk of fracture. Objective: To identify CT features associated with fracture of the metacarpophalangeal/metatarsophalangeal joint. Methods: Retrospective cohort study. Methods: Post-mortem CT images of 367 limbs from 157 Thoroughbred racehorses were graded for CT features. Multi...
Hagenbach M, Bierau J, Cruz AM, Koch C, Manso-Díaz G, Büttner K, Staszyk C, Röcken M.In the diagnostics of orthopedic diseases in the horse, diagnostic imaging often plays a decisive role. Cone beam computed tomography (CBCT) imaging is used in both human and small animal medicine and becoming increasingly popular. To see whether CBCT imaging can be useful in the diagnosis of orthopedic diseases of the carpal region of the horse and to explore possible limitations we compared CBCT images with multidetector computed tomography (MDCT) images of the carpal region of equine cadaveric specimens. Unassigned: Twenty-eight forelimbs from fifteen horses, slaughtered for reasons unrelat...
Godwin EE, Young NJ, Dudhia J, Beamish IC, Smith RK.Mesenchymal stem (progenitor; stromal) cell (MSC) therapy has gained popularity for the treatment of equine tendon injuries but without reports of long-term follow-up. Objective: To evaluate the safety and reinjury rate of racehorses after intralesional MSC injection in a large study of naturally occurring superficial digital flexor tendinopathy and to compare these data with those published for other treatments. Methods: Safety was assessed clinically, ultrasonographically, scintigraphically and histologically in a cohort of treated cases: 141 client-owned treated racehorses followed-up for a...
Fortier LA, Potter HG, Rickey EJ, Schnabel LV, Foo LF, Chong LR, Stokol T, Cheetham J, Nixon AJ.The purpose of this study was to compare the outcomes of treatment with bone marrow aspirate concentrate, a simple, one-step, autogenous, and arthroscopically applicable method, with the outcomes of microfracture with regard to the repair of full-thickness cartilage defects in an equine model. Methods: Extensive (15-mm-diameter) full-thickness cartilage defects were created on the lateral trochlear ridge of the femur in twelve horses. Bone marrow was aspirated from the sternum and centrifuged to generate the bone marrow concentrate. The defects were treated with bone marrow concentrate and mic...
Frisbie DD, Kisiday JD, Kawcak CE, Werpy NM, McIlwraith CW.The purpose of this study was the assessment of clinical, biochemical, and histologic effects of intraarticular administered adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. Osteoarthritis was induced arthroscopically in the middle carpal joint of all horses, the contralateral joint being sham-operated. All horses received treatment on Day 14. Eight horses received placebo treatment and eight horses received adipose-derived stromal vascular fraction in their osteoarthritis-affected joint. The final eight horses were treate...
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...
Smith RK, Werling NJ, Dakin SG, Alam R, Goodship AE, Dudhia J.Tendon injuries are a common age-related degenerative condition where current treatment strategies fail to restore functionality and normal quality of life. This disease also occurs naturally in horses, with many similarities to human tendinopathy making it an ideal large animal model for human disease. Regenerative approaches are increasingly used to improve outcome involving mesenchymal stem cells (MSCs), supported by clinical data where injection of autologous bone marrow derived MSCs (BM-MSCs) suspended in marrow supernatant into injured tendons has halved the re-injury rate in racehorses....
Carrade DD, Lame MW, Kent MS, Clark KC, Walker NJ, Borjesson DL.Mesenchymal stem cells (MSCs) derived from bone marrow (BM), adipose tissue (AT), umbilical cord blood (CB), and umbilical cord tissue (CT) are increasingly being used to treat equine inflammatory and degenerative lesions. MSCs modulate the immune system in part through mediator secretion. Animal species and MSC tissue of origin are both important determinants of MSC function. In spite of widespread clinical use, how equine MSCs function to heal tissues is fully unknown. In this study, MSCs derived from BM, AT, CB, and CT were compared for their ability to inhibit lymphocyte proliferation and ...
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...
Vidal MA, Walker NJ, Napoli E, Borjesson DL.Mesenchymal stem cells (MSCs) from adult and neonatal tissues are intensively investigated for their use in regenerative medicine. The purpose of this study was to compare the onset of replicative senescence in MSCs isolated from equine bone marrow (BMSC), adipose tissue (ASC), and umbilical cord tissue (UCMSC). MSC proliferation (cell doubling), senescence-associated β-galactosidase staining, telomere length, Sox-2, and lineage-specific marker expression were assessed for MSCs harvested from tissues of 4 different donors. The results show that before senescence ensued, all cell types prolife...
Schnabel LV, Pezzanite LM, Antczak DF, Felippe MJ, Fortier LA.The horse is a valuable species to assess the effect of allogeneic mesenchymal stromal cells (MSCs) in regenerative treatments. No studies to date have examined recipient response to major histocompatibility complex (MHC)-mismatched equine MSCs. The purposes of this study were to immunophenotype MSCs from horses of known MHC haplotype and to compare the immunogenicity of MSCs with differing MHC class II expression. Methods: MSCs and peripheral blood leukocytes (PBLs) were obtained from Thoroughbred horses (n=10) of known MHC haplotype (ELA-A2, -A3, and -A9 homozygotes). MSCs were cultured thro...
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...
Ferris DJ, Frisbie DD, Kisiday JD, McIlwraith CW, Hague BA, Major MD, Schneider RK, Zubrod CJ, Kawcak CE, Goodrich LR.To report outcome of horses with femorotibial lesions (meniscal, cartilage or ligamentous) treated with surgery and intra-articular administration of autologous bone marrow derived mesenchymal stem cells (BMSCs). Methods: Prospective case series. Methods: Horses (n = 33). Methods: Inclusion criteria included horses that had lameness localized to the stifle by diagnostic anesthesia, exploratory stifle arthroscopy and subsequent intra-articular administration of autologous BMSCs. Case details and follow-up were gathered from medical records, owner, trainer or veterinarian. Outcome was defined as...
Violini S, Ramelli P, Pisani LF, Gorni C, Mariani P.Mesenchymal stem cells (MSCs) have been recently investigated for their potential use in regenerative medicine. MSCs, in particular, have great potential, as in various reports they have shown pluripotency for differentiating into many different cell types. However, the ability of MSCs to differentiate into tendon cells in vitro has not been fully investigated. Results: In this study, we show that equine bone marrow mesenchymal stem cells (BM-MSCs), defined by their expression of markers such as Oct4, Sox-2 and Nanog, have the capability to differentiate in tenocytes. These differentiated cell...
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...
Ranera B, Lyahyai J, Romero A, Vázquez FJ, Remacha AR, Bernal ML, Zaragoza P, Rodellar C, Martín-Burriel I.Bone marrow and adipose tissue are the two main sources of mesenchymal stem cell (MSC). The aim of this work was to analyse the immunophenotype of 7 surface markers and the expression of a panel of 13 genes coding for cell surface markers in equine bone marrow and adipose tissue-derived MSCs obtained from 9 horses at third passage. The tri-lineage differentiation was confirmed by specific staining. Equine MSCs from both sources were positive for the MSC markers CD29 and CD90, while were negative for CD44, CD73, CD105, CD45 and CD34. The gene expression of these molecules was also evaluated by ...
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...
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 ...
Barberini DJ, Freitas NP, Magnoni MS, Maia L, Listoni AJ, Heckler MC, Sudano MJ, Golim MA, da Cruz Landim-Alvarenga F, Amorim RM.Studies with mesenchymal stem cells (MSCs) are increasing due to their immunomodulatory, anti-inflammatory and tissue regenerative properties. However, there is still no agreement about the best source of equine MSCs for a bank for allogeneic therapy. The aim of this study was to evaluate the cell culture and immunophenotypic characteristics and differentiation potential of equine MSCs from bone marrow (BM-MSCs), adipose tissue (AT-MSCs) and umbilical cord (UC-MSCs) under identical in vitro conditions, to compare these sources for research or an allogeneic therapy cell bank. Methods: The BM-MS...
Guest DJ, Smith MR, Allen WR.Autologous mesenchymal progenitor cells (MPCs) purified from bone marrow aspirates are being used in the treatment of superficial digital flexor tendon (SDFT) injuries in the horse with promising results. In this study the fate of autologous and allogeneic MPCs following injection into the SDFT was monitored by stable transfection of MPCs with green fluorescent protein (GFP). Small lesions were created manually in one forelimb SDFT of 2 horses and injected with autologous MPCs, allogeneic MPCs or bone marrow supernatant alone. Post mortem examinations performed after 10 or 34 days revealed GFP...
Smith RK.Optimal management of tendon overuse injuries in equine and human athletes should avoid the formation of excessive scar tissue, regenerate normal tendon matrix, and reduce re-injury rates. We hypothesized that the implantation of marrow-derived stromal stem cells (BM-MSCs), in far greater numbers than are present normally within tendon tissue, would synthesize a matrix more closely resembling tendon matrix than scar tissue, and hence increase the capacity to return to performance successfully. This article reviews the technique used clinically in the horse and the current outcome data for hors...
Radcliffe CH, Flaminio MJ, Fortier LA.Mesenchymal progenitor cells (MPCs) are often characterized using surface markers after expansion and treatment in culture. There are no studies directly comparing gene and protein markers in undifferentiated samples during the very early phases of culture. The goal of this study was to evaluate temporal gene and protein expression changes during establishment of equine MPC cultures. Bone marrow aspirate was obtained from 35 horses and processed by density gradient centrifugation. In freshly isolated bone marrow, mononuclear cells had variable expression of CD44, CD11a/CD18, CD90, and CD45RB c...
Arnhold SJ, Goletz I, Klein H, Stumpf G, Beluche LA, Rohde C, Addicks K, Litzke LF.To isolate and characterize bone marrow-derived equine mesenchymal stem cells (MSCs) for possible future therapeutic applications in horses. Methods: Equine MSCs were isolated from bone marrow aspirates obtained from the sternum of 30 donor horses. Methods: Cells were cultured in medium (alpha-minimum essential medium) with a fetal calf serum content of 20%. Equine MSC features were analyzed to determine selfrenewing and differentiation capacity. For potential therapeutic applications, the migratory potential of equine MSCs was determined. An adenoviral vector was used to determine the transdu...
de la Fuente J, Ayoubi P, Blouin EF, Almazán C, Naranjo V, Kocan KM.Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) causes human, equine and canine granulocytic anaplasmosis and tick-borne fever of ruminants. The rickettsia parasitizes granulocytes and bone marrow progenitor cells, and can be propagated in human promyelocytic and tick cell lines. In this study, microarrays of synthetic polynucleotides of 21,329 human genes were used to identify genes that are differentially expressed in HL-60 human promyelocytic cells in response to infection with A. phagocytophilum. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) of selec...
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 ...
Pigott JH, Ishihara A, Wellman ML, Russell DS, Bertone AL.Mesenchymal stem cells have demonstrated immunomodulatory capabilities as well as modest efficacy in animal models of joint injury, warranting further study as a potential treatment of joint disease. The goal of the study was to investigate the blood and synovial immune and histologic response to intra-articular injection of autologous, allogeneic, and xenogeneic bone marrow-derived mesenchymal stem cells (MSC) in horses. The study group consisted of 6 five-year-old Thoroughbred mares that had been injected previously with 15 million, genetically modified autologous, allogeneic, or xenogeneic ...
Hegewald AA, Ringe J, Bartel J, Krüger I, Notter M, Barnewitz D, Kaps C, Sittinger M.Mesenchymal stem cells (MSC) have the potential to differentiate into distinct mesenchymal tissues including cartilage, which suggest these cells as an attractive cell source for cartilage tissue engineering approaches. Our objective was to study the effects of TGF-beta1, hyaluronic acid and synovial fluid on chondrogenic differentiation of equine MSC. For that, bone marrow was aspirated from the tibia of one 18-month-old horse (Haflinger) and MSC were isolated using percoll-density centrifugation. To promote chondrogenesis, MSC were centrifuged to form a micromass and were cultured in a mediu...
Romero A, Barrachina L, Ranera B, Remacha AR, Moreno B, de Blas I, Sanz A, Vázquez FJ, Vitoria A, Junquera C, Zaragoza P, Rodellar C.Several therapies have been investigated for equine tendinopathies, but satisfactory long term results have not been achieved consistently and a better understanding of the healing mechanism elicited by regenerative therapies is needed. The aim of this study was to assess the separate effects of autologous bone marrow (BM) and adipose tissue (AT) derived mesenchymal stem cells (MSCs), and platelet rich plasma (PRP), for treating lesions induced in the superficial digital flexor tendon (SDFT) of horses. Lesions were created surgically in both SDFTs of the forelimbs of 12 horses and were treated...
Hoynowski SM, Fry MM, Gardner BM, Leming MT, Tucker JR, Black L, Sand T, Mitchell KE.Stem cells are being evaluated in numerous human clinical trials and are commercially used in veterinary medicine to treat horses and dogs. Stem cell differentiation, homing to disease sites, growth and cytokine factor modulation, and low antigenicity contribute to their therapeutic success. Bone marrow and adipose tissue are the two most common sources of adult-derived stem cells in animals. We report on the existence of an alternative source of primitive, multipotent stem cells from the equine umbilical cord cellular matrix (Wharton's jelly). Equine umbilical cord matrix (EUCM) cells can be ...
