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Topic:Bone Marrow
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.
Extracellular vesicles from equine mesenchymal stem cells decrease inflammation markers in chondrocytes in vitro. Mesenchymal stem cells (MSCs) have been used therapeutically in equine medicine. MSCs release extracellular vesicles (EVs), which affect cell processes by inhibiting cell apoptosis and regulating inflammation. To date, little is known about equine EVs and their regenerative properties. Objective: To characterise equine MSC-derived extracellular vesicles (EVs) and evaluate their effect on equine chondrocytes treated with pro-inflammatory cytokines in vitro. Methods: In vitro experiments with randomised complete block design. Methods: Mesenchymal stem cells from bone marrow, adipose tissue, and ...
Imaging and Gross Pathological Appearance of Changes in the Parasagittal Grooves of Thoroughbred Racehorses. (1) Background: Parasagittal groove (PSG) changes are often present on advanced imaging of racing Thoroughbred fetlocks and have been suggested to indicate increased fracture risk. Currently, there is limited evidence differentiating the imaging appearance of prodromal changes in horses at risk of fracture from horses with normal adaptive modelling in response to galloping. This study aims to investigate imaging and gross PSG findings in racing Thoroughbreds and the comparative utility of different imaging modalities to detect PSG changes. (2) Methods: Cadaver limbs were collected from twenty ...
Immune response to allogeneic equine mesenchymal stromal cells. Mesenchymal stromal cells (MSCs) are believed to be hypoimmunogeneic with potential use for allogeneic administration. Bone marrow was harvested from Connemara (n = 1), Standardbred (n = 6), and Thoroughbred (n = 3) horses. MSCs were grouped by their level of expression of major histocompatibility factor II (MHC II). MSCs were then sub-grouped by those MSCs derived from universal blood donor horses. MSCs were isolated and cultured using media containing fetal bovine serum until adequate numbers were acquired. The MSCs were cultured in xenogen-free media for 48 h prior to use and d...
The anti-inflammatory effects of equine bone marrow stem cell-derived extracellular vesicles on autologous chondrocytes. Osteoarthritis (OA) in the horse is an economic and welfare issue and there are no current disease modifying drugs available. Stem cells have been suggested as a therapeutic intervention for OA, originally on the basis of their regenerative capacity. However, it is hypothesised that mesenchymal stem cells (MSC) exert their effects via paracrine factors including the production of extracellular vesicles that can themselves recapitulate the MSC effects in the joint. Objective: To isolate extracellular vesicles from bone marrow MSC and investigate their anti-inflammatory effects on chondrocytes. ...
Engrafting Horse Immune Cells into Mouse Hosts for the Study of the Acute Equine Immune Responses. Immunological studies in the horse are frequently hampered by lack of environmental control, complicated study design, and ethical concerns when performing high risk studies. The purpose of the current study was to investigate the utility of a xenograft model for studying acute equine immune responses. Immunocompromised non obese diabetic (NOD). sudden combined immunodeficiency (scid).gamma-/- (NSG) mice were engrafted with either equine peripheral blood lymphocytes (PBLs) or equine bone marrow to determine an optimal protocol for equine lymphocyte engraftment. We found that both PBL and bone ...
Development of a biologically immortalized equine stem cell line. Bone repair in horses implies invasive surgeries and increased cost. Research on musculoskeletal disorders therapy in horses includes cell-based therapy with mesenchymal stromal cells (MSCs). Mesenchymal stromal cells can be obtained from bone marrow (BMMSCs). Unfortunately, BMMSCs have limited cell replication . The objective of this study was to develop a biologically immortalized equine stem cell line derived from bone marrow, with unlimited proliferation and the ability to differentiate into bone cells. Equine BMMSCs were transfected and immortalized with human telomerase reverse transcri...
Tissue predictability of elastography is low in collagenase induced deep digital flexor tendinopathy. Elastography is an emerging imaging modality for characterizing tendon injury in horses, but its ability to differentiate tissue deformability relative to treatment group and biochemical properties using a prospective, experimental study design remain unknown. Objectives of the current study were to (a) to investigate differences in glycosaminoglycan, DNA, and soluble collagen levels in mesenchymal stem cell (MSC) treated limbs compared to untreated control limbs utilizing a collagenase model of tendinopathy; (b) compare elastographic features between treatment groups; and (c) determine tissue...
Isolation and morphological characterization of equine mesenchymal stem cells from harvested adipose tissue and bone marrow and stably transfected with green fluorescent protein. To characterize the ultrastructure of mesenchymal stem cells (MSCs) that were harvested from the adipose tissue (AT-MSCs) and bone marrow (BM-MSCs) of horses and transfected with green fluorescent protein. Methods: MSCs from adipose tissue and bone marrow of 6 adult female Hispano-Bretón horses. Methods: Harvested equine MSCs were cultivated and transfected with green fluorescent protein, and the immunophenotypes of the MSCs were characterized by use of anti-CD90 and anti-CD105 monoclonal antibodies. When stable transfection of MSCs was achieved, the morphological and ultrastructural characte...
Chondrogenic potential of mesenchymal stem cells from horses using a magnetic 3D cell culture system. Mesenchymal stem cells (MSCs) represent a promising therapy for the treatment of equine joint diseases, studied due to their possible immunomodulatory characteristics and regenerative capacity. However, the source of most suitable MSCs for producing cartilage for regenerative processes in conjunction with biomaterials for an enhanced function is yet to be established. Objective: To compare the chondrogenicity of MSCs derived from synovial fluid, bone marrow, and adipose tissue of horses, using the aggrecan synthesis. Methods: MSCs from ten horses were cultured, phenotypic characterization was ...
Effectiveness of Platelet-Rich Plasma and Bone Marrow Aspirate Concentrate as Treatments for Chronic Hindlimb Proximal Suspensory Desmopathy. This retrospective study aimed to evaluate the clinical effect of bone marrow aspirate concentrate (BMAC) and leukocyte rich PRP (LR-PRP) compared to horses undergoing controlled exercise alone in horses with >3 months proximal suspensory desmopathy in hindlimbs (HPSD). Nighty-three horses were divided into three groups according to the treatment: a control (n = 22), LR-PRP (n = 46), and BMAC (n = 25) group. Lameness and ultrasound scores were recorded before treatment (T0) and at 6 months (T1) post-treatment. Records horses considered sound at evaluation and level of performance were addit...
Effects of Normal Synovial Fluid and Interferon Gamma on Chondrogenic Capability and Immunomodulatory Potential Respectively on Equine Mesenchymal Stem Cells. 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 ...
Tenogenic Potential of Equine Fetal Mesenchymal Stem Cells Under The In Vitro Effect of Bone Morphogenetic Protein-12 (BMP-12). Equine adult bone marrow-derived MSCs (BM-MSCs) may be induced into the tenogenic lineage after exposure with bone morphogenetic protein-12 (BMP-12). Despite fetal BM-MSCs have showed a greater differentiation potential compared to adults, the tenogenic differentiation capacity of equine fetal BM-MSC have not been reported. Thus, the aim of the present study was to evaluate the in vitro tenogenic differentiation potential of equine fetal BM-MSCs under the effect of BMP-12. Equine fetal BM-MSCs were exposed to three concentrations of BMP-12 (25, 50 and 100 ng/mL) during a 21-day culture period....
A retrospective preliminary histomorphometric and clinical investigation on sinus augmentation using enzyme-deantigenic, collagen-preserving equine bone granules and plasma rich in growth factors. 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...
Adeno-Associated Virus-Mediated Overexpression of Interleukin-10 Affects the Immunomodulatory Properties of Equine Bone Marrow-Derived Mesenchymal Stem Cells. Joint injury can cause posttraumatic inflammation, which if severe enough can lead to posttraumatic osteoarthritis (PTOA), a progressive and debilitating condition. Posttraumatic inflammation is characterized by an influx of T lymphocytes and upregulation of inflammatory cytokines and degradative enzymes by activated chondrocytes and synoviocytes. Intra-articular bone marrow-derived mesenchymal stem cell (BM-MSC) injection for the treatment of osteoarthritis (OA) has been of interest due to the immunomodulatory properties of these cells. Interleukin (IL)-10, a potent immunomodulatory cytokine,...
A review of current knowledge of myeloproliferative disorders in the horse. Myeloid disorders are conditions being characterized by abnormal proliferation and development of myeloid lineage including granulocytes (neutrophils, eosinophils and basophils), monocytes, erythroids, and megakaryocytes precursor cells. Myeloid leukemia, based on clinical presentation and proliferative rate of neoplastic cells, is divided into acute (AML) and myeloproliferative neoplasms (MPN). The most commonly myeloid leukemia reported in horses are AML-M4 (myelomonocytic) and AML-M5 (monocytic). Isolated cases of AML-M6B (acute erythroid leukemia), and chronic granulocytic leukemia have al...
Development of novel gene carrier using modified nano hydroxyapatite derived from equine bone for osteogenic differentiation of dental pulp stem cells. Hydroxyapatite (HA) is a representative substance that induces bone regeneration. Our research team extracted nanohydroxyapatite (EH) from natural resources, especially equine bones, and developed it as a molecular biological tool. Polyethylenimine (PEI) was used to coat the EH to develop a gene carrier. To verify that PEI is well coated in the EH, we first observed the morphology and dispersity of PEI-coated EH (pEH) by electron microscopy. The pEH particles were well distributed, while only the EH particles were not distributed and aggregated. Then, the existence of nitrogen elements of PEI ...
Effects of continuous passage on the immunomodulatory properties of equine bone marrow-derived mesenchymal stem cells in vitro. The immunomodulatory properties of mesenchymal stem cells (MSCs) have been studied extensively due to their increasing clinical application for tissue regeneration and repair following culture expansion. We have studied the effect of continuous passage on the immunomodulatory capacity of equine bone marrow-derived MSCs (BM-MSCs). Equine BM-MSCs were isolated and culture expanded to passage three, six, and nine (P3, P6, P9). Immunomodulatory properties of each passage were assessed using a T cell proliferation assay and cytokine synthesis following stimulation with interferon gamma (IFN-γ). Re...
TGF-β2 Reduces the Cell-Mediated Immunogenicity of Equine MHC-Mismatched Bone Marrow-Derived Mesenchymal Stem Cells Without Altering Immunomodulatory Properties. Allogeneic mesenchymal stem cells (MSCs) are a promising cell therapy for treating numerous diseases, but major histocompatibility complex (MHC)-mismatched MSCs can be rejected by the recipient's immune system. Pre-treating MSCs with transforming growth factor-β2 (TGF-β2) to downregulate surface expression of MHC molecules may enhance the ability of allogeneic MSCs to evade immune responses. We used lymphocyte proliferation assays and ELISAs to analyze the immunomodulatory potential of TGF-β2-treated equine bone marrow-derived MSCs. T cell activation and cytotoxicity assays were then used t...
The effect of equine bone marrow-derived mesenchymal stem cells on the expression of apoptotic genes in neutrophils. Bone marrow mesenchymal stem cells (BM-MSCs), as multipotent cells with self-renewal and plastic-adherent properties, have immunomodulatory effects on immune cells, including neutrophils. These cells are in close proximity in bone marrow (BM) sinusoids with non-multiplicative immature neutrophils. BM-MSCs exert their immunomodulatory effects on adjacent cells both directly (cell-to-cell contact) and indirectly (secretion of soluble factors). The aim of this study was to evaluate the effect of equine bone marrow mesenchymal stem cells (BM-MSCs) on the expression of some pro- and anti-apoptotic ...
Comparative Analysis of Tenogenic Gene Expression in Tenocyte-Derived Induced Pluripotent Stem Cells and Bone Marrow-Derived Mesenchymal Stem Cells in Response to Biochemical and Biomechanical Stimuli. 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...
Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age. 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...
Do allogeneic bone marrow derived mesenchymal stem cells diminish the inflammatory response to lipopolysaccharide infusion in horses? A pilot study. Endotoxemia is a leading cause of morbidity and mortality in the equine industry, with colic being the most common cause of endotoxemia in horses. The objective of this study was to evaluate the safety and potential efficacy of a single dose of allogeneic equine bone marrow derived mesenchymal stem cells (BM-MSCs) in horses after the IV administration of lipopolysaccharide (LPS). Six horses were administered an IV infusion of 30 ng/kg LPS (O55:B5 Escherichia coli) in 500 ml saline over 30 min. Immediately after infusion test horses (n = 3) were administered 100 × 10 allogeneic BM-MSCs diluted...
Nanoparticles from Equine Fetal Bone Marrow-Derived Cells Enhance the Survival of Injured Chondrocytes. Recent studies have shown that mesenchymal stem cells (MSCs) can play a restorative role against degenerative joint diseases in horses. The purpose of this study was to investigate whether fetal bone marrow-derived cells (BMC)-derived nanoparticles (BMC-NPs) can stimulate the survival of equine chondrocytes. Equine fetal BMCs were isolated and characterized, and the role of BMC-NPs s in equine chondrocytes undergoing inflammatory cell death was examined. BMCs have several characteristics, such as the potential to differentiate into chondrocytes and osteocytes. Additionally, BMCs expressed immu...
Horizontal bone grafting using equine-derived cancellous bone blocks is associated with severe complications: A prospective clinical and histological pilot study. The aim of this prospective, clinical study was to evaluate the clinical performance and histological outcome of a new equine hydroxyapatite collagenated bone block (eHAC) for horizontal bone grafting prior to implant placement. Methods: Five patients (two male/three female) with a mean age of 51.6 years (range 22-66 years) and a reduced horizontal bone width of the alveolar ridge (mean 3.5 mm) underwent horizontal bone grafting using eHAC at 10 grafting sites. Reentry was performed 6.9 months after the horizontal grafting procedure. Clinical follow-up (mean 28.9 month) considered width g...
Tough magnesium phosphate-based 3D-printed implants induce bone regeneration in an equine defect model. One of the important challenges in bone tissue engineering is the development of biodegradable bone substitutes with appropriate mechanical and biological properties for the treatment of larger defects and those with complex shapes. Recently, magnesium phosphate (MgP) doped with biologically active ions like strontium (Sr) have shown to significantly enhance bone formation when compared with the standard calcium phosphate-based ceramics. However, such materials can hardly be shaped into large and complex geometries and more importantly lack the adequate mechanical properties for the treatment ...
One health in regenerative medicine: report on the second Havemeyer symposium on regenerative medicine in horses. Regenerative medicine is commonly used in human and equine athletes. Potential therapies include culture expanded stem cells, stromal vascular fraction of adipose tissue, platelet-rich plasma, bone marrow concentrate, or autologous conditioned serum. The purpose of this manuscript is to disseminate findings from a workshop on the development of translational regenerative medicine in the equine field. Five themes emerged: stem cell characterization and tenogenic differentiation; interactions between mesenchymal stem cells, other cells and the environment; scaffolds and cell packaging; blood- an...
Quality control and immunomodulatory potential for clinical-grade equine bone marrow-derived mesenchymal stromal cells and conditioned medium. This study aimed to assess the safety and reproducibility of cell therapy for its use in clinical practice. We performed immunophenotypic characterization of equine bone marrow-derived mesenchymal stromal cells (BMMSCs) by flow cytometry using CD90, CD19, CD14, CD105, CD45, and HLA-DR markers (n = 4); GTG banding cytogenetic analysis (n = 3); and microbiological quality control (n = 4). The immunomodulatory potentials of BMMSCs (n = 4) and its conditioned medium (CM, n = 3) were investigated by in vitro lymphocyte inhibition assay using phytohemagglutinin (PHA)-stimulated peripheral ...
Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis. Pegiviruses frequently cause persistent infection (as defined by >6 months), but unlike most other Flaviviridae members, no apparent clinical disease. Human pegivirus (HPgV, previously GBV-C) is detectable in 1-4% of healthy individuals and another 5-13% are seropositive. Some evidence for infection of bone marrow and spleen exists. Equine pegivirus 1 (EPgV-1) is not linked to disease, whereas another pegivirus, Theiler's disease-associated virus (TDAV), was identified in an outbreak of acute serum hepatitis (Theiler's disease) in horses. Although no subsequent reports link TDAV to disease,...
Pre-conditioning of Equine Bone Marrow-Derived Mesenchymal Stromal Cells Increases Their Immunomodulatory Capacity. Mesenchymal stem/stromal cells (MSCs) are increasingly explored for the treatment of degenerative and inflammatory diseases in human and veterinary medicine. One of the key characteristics of MSCs is that they modulate inflammation mainly through the secretion of soluble mediators. However, despite widespread clinical use, knowledge regarding the effector mechanisms of equine MSCs, and consequently their effectiveness in the treatment of diseases, is still unknown. The objectives of this study were to determine the mechanisms underlying inhibition of lymphocyte proliferation by equine bone mar...
