Mesenchymal cells are multipotent stromal cells found in horses that have the ability to differentiate into various cell types, including osteoblasts, chondrocytes, and adipocytes. These cells are present in multiple tissues, such as bone marrow, adipose tissue, and umbilical cord blood. Mesenchymal cells contribute to tissue repair and regeneration and are involved in modulating the immune response. Their potential for differentiation and self-renewal makes them a subject of interest in regenerative medicine and therapeutic applications in equine health. This page compiles peer-reviewed research studies and scholarly articles that explore the characteristics, differentiation potential, and therapeutic applications of mesenchymal cells in horses.
Cequier A, Romero A, Vázquez FJ, Vitoria A, Bernad E, Fuente S, Zaragoza P, Rodellar C, Barrachina L.Immunomodulation and immunogenicity are pivotal aspects for the therapeutic use of mesenchymal stem cells (MSCs). Since the horse is highly valuable as both a patient and translational model, further knowledge on equine MSC immune properties is required. This study analysed how inflammation, chondrogenic differentiation and compatibility for the major histocompatibility complex (MHC) influence the MSC immunomodulatory-immunogenicity balance. Equine MSCs in basal conditions, pro-inflammatory primed (MSC-primed) or chondrogenically differentiated (MSC-chondro) were co-cultured with either autolo...
Roth SP, Burk J, Brehm W, Troillet A.Mesenchymal stromal cells (MSC) represent a promising treatment option for tendon disorders and joint diseases, primarily osteoarthritis. Since MSC are highly context-sensitive to their microenvironment, their therapeutic efficacy is influenced by their tissue-specific pathologically altered targets. These include not only cellular components, such as resident cells and invading immunocompetent cells, but also components of the tissue-characteristic extracellular matrix. Although numerous models have already shown potential MSC-related mechanisms of action in tendon and joint diseases, only a...
Regenerative medicine applied to skin lesions is a field in constant improvement. The use of biomaterials with integrin agonists could promote cell adhesion increasing tissue repair processes. The aim of this pilot study was to analyze the effect of an α4β1 integrin agonist on cell adhesion of equine adipose tissue (AT) and Wharton's jelly (WJ) derived MSCs and to investigate their adhesion ability to GM18 incorporated poly L-lactic acid (PLLA) scaffolds. Adhesion assays were performed after culturing AT- and WJ-MSCs with GM18 coating or soluble GM18. Cell adhesion on GM18 containing PLLA sc...
Depuydt E, Broeckx SY, Chiers K, Patruno M, Da Dalt L, Duchateau L, Saunders J, Pille F, Martens A, Van Hecke L, Spaas JH.The use of mesenchymal stem cells (MSCs) for the treatment of equine tendon disease is widely investigated because of their regenerative and immunomodulatory potential. However, questions have been raised concerning the immunogenic properties of allogeneic MSCs. Therefore, two studies were conducted to assess the safety of equine allogeneic peripheral blood-derived tenogenic primed MSCs (tpMSCs). The objective was to evaluate if a single and repeated tpMSC administration induced a cellular and humoral immune response in horses suffering from tendon injuries. Horses enrolled in the first study ...
Melotti L, Carolo A, Elshazly N, Boesso F, Da Dalt L, Gabai G, Perazzi A, Iacopetti I, Patruno M.In the present case report a show jumping 10-year-old Sella Italiano gelding, presented with severe lameness, swelling and pain at palpation of the mid-metacarpal region of the left forelimb. Clinical and ultrasound examination diagnosed a chronic tendonitis of the central region of the superficial digital flexor tendon (SDFT). The lesion was a reoccurrence since it developed from a previously healed injury. The horse had to stop competing and was unresponsive to gold-standard treatments as Non-steroidal anti-inflammatory drugs (NSAIDs) and conservative management after 6 months of therapy. Th...
Klein CE, Bramlage LR, Stefanovski D, Ruggles AJ, Embertson RM, Hopper SA.To compare 3 different methods for treatment of medial femoral condyle (MFC) subchondral cystic lesions in Thoroughbred horses <24 months old based on the criterion of ability to race post-treatment. Methods: Retrospective cohort study. Methods: Thoroughbreds (n = 107, age < 24 months) diagnosed with MFC subchondral cystic lesions. Methods: Medical records between January 2004 and December 2017 were reviewed. Three treatment methods were used in these horses during that time frame: arthroscopic debridement, intralesional autologous mesenchymal stem cell (MSC) injection, and int...
Murata D, Ishikawa S, Sunaga T, Saito Y, Sogawa T, Nakayama K, Hobo S, Hatazoe T.Medical interventions for subchondral bone cysts in horses have been extensively studied. This study investigated the regeneration of articular cartilage and subchondral bone with scaffold-free three-dimensional (3D) constructs of equine synovial membrane-derived mesenchymal stem cells (SM-MSCs) isolated from three ponies and expanded until over 1.0 × 10 cells at passage 2 (P2). Results: SM-MSCs were strongly positive for CD11a/CD18, CD44, and major histocompatibility complex (MHC) class I; moderately positive for CD90, CD105, and MHC class II; and negative for CD34 and CD45 on flow cytom...
Adamič N, Prpar Mihevc S, Blagus R, Kramarič P, Krapež U, Majdič G, Viel L, Hoffman AM, Bienzle D, Vengust M.Severe equine asthma (SEA) is a common chronic respiratory disease and a significant health and well-being problem in horses. Current therapeutic strategies improve pulmonary function and clinical signs in some horses, but in the long-term, return to full athletic function appears to be rare. The aim of this study was to assess the safety and the effect of intrabronchial administration of adipose-derived mesenchymal stem cells (AD-MSC) on pulmonary inflammatory and clinical parameters in horses with SEA. This was a randomized controlled trial. Twenty adult horses diagnosed with SEA were random...
Hagen A, Holland H, Brandt VP, Doll CU, Häußler TC, Melzer M, Moellerberndt J, Lehmann H, Burk J.Platelet lysate (PL) is an attractive platelet-based therapeutic tool and has shown promise as xeno-free replacement for fetal bovine serum (FBS) in human and equine mesenchymal stromal cell (MSC) culture. Here, we established a scalable buffy-coat-based protocol for canine PL (cPL) production (n = 12). The cPL was tested in canine adipose MSC (n = 5) culture compared to FBS. For further comparison, equine adipose MSC (n = 5) were cultured with analogous equine PL (ePL) or FBS. During canine blood processing, platelet and transforming growth factor-β1 concentrations increased ( < 0.05 and < ...
Avellar HK, Lutter JD, Ganta CK, Beard W, Smith JR, Jonnalagadda N, Peloquin S, Kang Q, Ayub K.Septic arthritis is considered a medical emergency. Disease following bacterial colonization can lead to significant morbidity and mortality and requires costly treatment. Antimicrobial properties of regenerative therapies, including mesenchymal stromal cells and platelet products, have been researched extensively in human medicine. Although fewer studies have been conducted in veterinary species, they have shown promising results. The purpose of this study was to evaluate bacterial suppression by equine platelet lysate (EPL) and adipose-derived mesenchymal stromal cells (ASCs) in vitro. We hy...
Di Francesco P, Cajon P, Desterke C, Perron Lepage MF, Lataillade JJ, Kadri T, Lepage OM.To assess the clinical value and safety of the application of allogeneic equine oral mucosa mesenchymal stromal cells (OM-MSCs) to wounds. Animals. 8 healthy adult horses without front limb skin lesions or musculoskeletal disease. Procedures. Stem cells were isolated from the oral mucosa of a donor horse. Horses were subjected to the creation of eight full-thickness cutaneous wounds, two on each distal forelimb (FL) and two on both sides of the thorax (TH). Each wound was subjected to one out of four treatments: no medication (T1), hyaluronic acid- (HA-) gel containing OM-MSC (T2), HA-gel cont...
Lee OJ, Koch TG.Inflammation-associated disorders are significant causes of morbidity in horses. Equine single-donor mesenchymal stromal cells (sdMSCs) hold promise as cell-therapy candidates due to their secretory nonprogenitor functions. This has been demonstrated by mononuclear cell suppression assays (MSAs) showing that sdMSCs are blood mononuclear cell (BMC) suppressive in vitro. sdMSCs derived from umbilical cord blood are of clinical interest due to their ease of procurement, multipotency, and immunomodulatory ability. Due to the inherent donor-to-donor heterogeneity of MSCs, the development of robust ...
Doll CU, Niebert S, Burk J.Tendon lesions are common sporting injuries in humans and horses alike. The healing process of acute tendon lesions frequently results in fibrosis and chronic disease. In horses, local mesenchymal stromal cell (MSC) injection is an accepted therapeutic strategy with positive influence on acute lesions. Concerning the use of MSCs in chronic tendon disease, data are scarce but suggest less therapeutic benefit. However, it has been shown that MSCs can have a positive effect on fibrotic tissue. Therefore, we aimed to elucidate the interplay of MSCs and healthy or chronically diseased tendon matrix...
Arévalo-Turrubiarte M, Baratta M, Ponti G, Chiaradia E, Martignani E.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 ...
Kamm JL, Riley CB, Parlane NA, Gee EK, McIlwraith CW.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...
Hotham WE, Thompson C, Szu-Ting L, Henson FMD.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. ...
Mund SJK, MacPhee DJ, Campbell J, Honaramooz A, Wobeser B, Barber SM.Limb wounds are common in horses and often develop complications. Intravenous multipotent mesenchymal stromal cell (MSC) therapy is promising but has risks associated with intravenous administration and unknown potential to improve cutaneous wound healing. The objectives were to determine the clinical safety of administering large numbers of allogeneic cord blood-derived MSCs intravenously, and if therapy causes clinically adverse reactions, accelerates wound closure, improves histologic healing, and alters mRNA expression of common wound cytokines. Wounds were created on the metacarpus of 12 ...
Harman RM, Churchill KA, Jager MC, Van de Walle GR.Equid herpesvirus 1 (EHV-1) outbreaks occur when virus spreads from infected horses to in-contact horses, primarily via nasal shedding. This study evaluated the efficacy of factors secreted by equine peripheral blood derived mesenchymal stromal cells (PB-MSCs), collectively named the secretome, to inhibit the growth of EHV-1 in (i) 2D epithelial cell cultures (RK-13) in vitro, (ii) 3D equine nasal explants in vitro and (iii) an EHV-1 infection mouse model in vivo. The PB-MSC secretome was found to inhibit EHV-1 in RK-13 cells as well as in the epithelium of equine nasal explants. Although the ...
Melzer M, Schubert S, Müller SF, Geyer J, Hagen A, Niebert S, Burk J.Mesenchymal stromal cells (MSC) represent a promising therapeutic tool for tendon regeneration. Their tenogenic differentiation is crucial for tissue engineering approaches and may support their beneficial effects after cell transplantation . The transforming growth factor (TGF)-, signalling via intracellular Smad molecules, is a potent paracrine mediator of tenogenic induction. Moreover, scaffold topography or tendon matrix components induced tenogenesis via activation of the Rho/ROCK cascade, which, however, is also involved in pathological adaptations in extracellular matrix pathologies. Th...
Nino-Fong R, Esparza Gonzalez BP, Rodriguez-Lecompte JC, Montelpare W, McD￮ L.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...
Johnson SA, Biscoe EW, Eilertson KE, Lutter JD, Schneider RK, Roberts GD, Cary JA, Frisbie DD.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...
Pérez-Castrillo S, González-Fernández ML, Gutiérrez-Velasco L, Villar-Suárez V.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...
Van Hecke L, Magri C, Duchateau L, Beerts C, Geburek F, Suls M, Da Dalt L, Patruno M, Saunders J, Broeckx SY, Depuydt E, Spaas JH.The use of mesenchymal stem cells (MSCs) for the treatment of equine joint disease is widely investigated because of their regenerative and immunomodulatory potential. Allogeneic MSCs provide a promising alternative to autologous MSCs, since the former are immediately available and enable a thorough donor screening. However, questions have been raised concerning the immunogenic potential of allogeneic MSCs, especially after repeated administration. Methods: Current retrospective study assessed the cellular and humoral immunogenicity of ten jumping and dressage horses with naturally occurring d...
Prządka P, Buczak K, Frejlich E, Gąsior L, Suliga K, Kiełbowicz Z.Regenerative medicine is a dynamically developing field of human and veterinary medicine. The animal model was most commonly used for mesenchymal stem cells (MSCs) treatment in experimental and preclinical studies with a satisfactory therapeutic effect. Year by year, the need for alternative treatments in veterinary medicine is increasing, and other applications for promising MSCs and their biological derivatives are constantly being sought. There is also an increase in demand for other methods of treating disease states, of which the classical treatment methods did not bring the desired resul...
Fülber J, Agreste FR, Seidel SRT, Sotelo EDP, Barbosa ÂP, Michelacci YM, Baccarin RYA.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 ...
Zayed M, Adair S, Dhar M.Synovial fluid contains cytokines, growth factors and resident mesenchymal stem cells (MSCs). The present study aimed to (1) determine the effects of autologous and allogeneic synovial fluid on viability, proliferation and chondrogenesis of equine bone marrow MSCs (BMMSCs) and (2) compare the immunomodulatory properties of equine synovial fluid MSCs (SFMSCs) and BMMSCs after stimulation with interferon gamma (INF-γ). To meet the first aim of the study, the proliferation and viability of MSCs were evaluated by MTS and calcein AM staining assays. To induce chondrogenesis, MSCs were cultured in ...
Oliva R, Núñez I, Segunda MN, Peralta OA.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....
Lovati AB, Corradetti B, Lange Consiglio A, Recordati C, Bonacina E, Bizzaro D, Cremonesi F.Mesenchymal stem cells have been recently investigated for their potential use in regenerative medicine. Population of adult stem cells were recently identified in human and lab animal tendons, but no detailed investigations have been made in the equine species. The aim of our study is to identify a progenitor cell population from tendon tissue (TSPCs) in the horse superficial digital flexor tendon that are able to be highly clonogenic, to grow fast and to differentiate in different induced cell lineages as well as bone marrow derived progenitor cells (BM-MSCs). The hypothesis that TSPCs posse...
Fortier LA, Nixon AJ, Williams J, Cable CS.To isolate mesenchymal stem cells from adult horses and determine specific monolayer culture conditions required to enhance biochemically and phenotypically defined chondrocytic differentiation. Methods: 2 adult horse bone marrow donors without skeletal or hematologic abnormalities. Methods: Bone marrow was aspirated from the sternebra, and mesenchymal stem cells were isolated by centrifugation and cultured in monolayers. Subcultures were established in 24-well plates on day 13. Culture medium was harvested every 2 days, and culture of 12 of the 24 wells was terminated on day 6 and of the rema...
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...
Alicka M, Kornicka-Garbowska K, Kucharczyk K, Kępska M, Rӧcken M, Marycz K.Progressive loss of cell functionality caused by an age-related impairment in cell metabolism concerns not only mature specialized cells but also its progenitors, which significantly reduces their regenerative potential. Adipose-derived stem cells (ASCs) are most commonly used in veterinary medicine as an alternative treatment option in ligaments and cartilage injuries, especially in case of high-value sport horses. Therefore, the main aim of this study was to identify the molecular alternations in ASCs derived from three age-matched horse groups: young ( 15 years old). ASCs were isolated ...
Marycz K, Weiss C, Śmieszek A, Kornicka K.Mesenchymal stem cells (MSCs) are frequently used in both human and veterinary medicine because their unique properties, such as modulating the immune response and differentiating into multiple lineages, make them a valuable tool in cell-based therapies. However, many studies have indicated the age-, lifestyle-, and disease-related deterioration of MSC regenerative characteristics. However, it still needs to be elucidated how the patient's health status affects the effectiveness of MSC differentiation. In the present study, we isolated mesenchymal stem cells from adipose tissue (adipose-derive...
Barrachina L, Remacha AR, Romero A, Vázquez FJ, Albareda J, Prades M, Ranera B, Zaragoza P, Martín-Burriel I, Rodellar C.Mesenchymal stem cells (MSCs) are being investigated for the treatment of equine joint diseases because of their regenerative potential. Recently, the focus mainly has addressed to their immunomodulatory capacities. Inflammation plays a central role in joint pathologies, since the release of proinflammatory mediators to the synovial fluid (SF) leads to the activation of enzymatic degradation of the cartilage. MSCs can modulate the local immune environment through direct or paracrine interaction with immune cells, suppressing their proliferation and re-addressing their functions. Proinflammator...
Vézina Audette R, Lavoie-Lamoureux A, Lavoie JP, Laverty S.Osteoarthritis (OA) is a degenerative disease of joint tissues that causes articular cartilage erosion, osteophytosis and loss of function due to pain. Inflammation and inflammatory cytokines in synovial fluid (SF) contribute to OA progression. Intra-articular (IA) injections of multipotent mesenchymal stromal cells (MSCs) are employed to treat OA in both humans and animals. MSCs secrete paracrine pro-inflammatory and anabolic signaling molecules that promote tissue repair. The objective of this study was to investigate the effects of OASF on the gene expression of paracrine signaling molecule...
Ardanaz N, Vázquez FJ, Romero A, Remacha AR, Barrachina L, Sanz A, Ranera B, Vitoria A, Albareda J, Prades M, Zaragoza P, Martín-Burriel I....Mesenchymal stem cells (MSCs) transplantation has become a promising therapeutic choice for musculoskeletal injuries. Joint-related disorders are highly prevalent in horses. Therefore, these animals are considered as suitable models for testing MSC-based therapies for these diseases. The aim of this study was to investigate the clinical and inflammatory responses to intra-articular single and repeat dose administration of autologous or of pooled allogeneic MSCs in healthy equine healthy joints. Six horses were intra-articularly injected with a single autologous dose of bone marrow derived MSCs...
Roth SP, Glauche SM, Plenge A, Erbe I, Heller S, Burk J.Decellularization of tendon tissue plays a pivotal role in current tissue engineering approaches for in vitro research as well as for translation of graft-based tendon restoration into clinics. Automation of essential decellularization steps like freeze-thawing is crucial for the development of more standardized decellularization protocols and commercial graft production under good manufacturing practice (GMP) conditions in the future. In this study, a liquid nitrogen-based controlled rate freezer was utilized for automation of repeated freeze-thawing for decellularization of equine superficia...
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...
Crovace A, Lacitignola L, Rossi G, Francioso E.The aim of this study was to compare treatment with cultured bone marrow stromal cells (cBMSCs), bone marrow Mononucleated Cells (BMMNCs), and placebo to repair collagenase-induced tendinitis in horses. In six adult Standardbred horses, 4000 IU of collagenase were injected in the superficial digital flexor tendon (SDFT). Three weeks after collagenase treatment, an average of either 5.5 x 10(6) cBMSCs or 1.2 x 10(8) BMMNCs, fibrin glue, and saline solution was injected intralesionally in random order. In cBMSC- and BMMNCS-treated tendons, a high expression of cartilage oligomeric matrix protein...
Paebst F, Piehler D, Brehm W, Heller S, Schroeck C, Tárnok A, Burk J.Horses are an approved large animal model for therapies of the musculoskeletal system. Especially for tendon disease where cell-based therapy is commonly used in equine patients, the translation of achieved results to human medicine would be a great accomplishment. Immunophenotyping of equine mesenchymal stromal cells (MSCs) remains the last obstacle to meet the criteria of the International Society for Cellular Therapy (ISCT) definition of human MSCs. Therefore, the surface antigen expression of CD 29, CD 44, CD 73, CD 90, CD 105, CD 14, CD 34, CD 45, CD 79α, and MHC II in equine MSCs from a...
Degenerative joint disease is one of the main causes of equine early retirement from pleasure riding or a performance career. The disease is initially triggered by an abnormal loading of normal cartilage or a normal loading of abnormal cartilage. This primary insult is accompanied with joint inflammation, which leads to further progressive degeneration of the articular cartilage and changes in the surrounding tissues. Therefore, in search for an effective treatment, 75 adult horses with early signs of degenerative fetlock joint disease were enrolled in a randomized, multicenter, double-blinded...
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....
Radtke CL, Nino-Fong R, Esparza Gonzalez BP, Stryhn H, McD￮ LA.To characterize equine muscle tissue- and periosteal tissue-derived cells as mesenchymal stem cells (MSCs) and assess their proliferation capacity and osteogenic potential in comparison with bone marrow- and adipose tissue-derived MSCs. Methods: Tissues from 10 equine cadavers. Methods: Cells were isolated from left semitendinosus muscle tissue, periosteal tissue from the distomedial aspect of the right tibia, bone marrow aspirates from the fourth and fifth sternebrae, and adipose tissue from the left subcutaneous region. Mesenchymal stem cells were characterized on the basis of morphology, ad...
Braun J, Hack A, Weis-Klemm M, Conrad S, Treml S, Kohler K, Walliser U, Skutella T, Aicher WK.To evaluate the proliferative behavior, telomere length, immunophenotype, and differentiation capacity of equine adipose tissue-derived mesenchymal stem cells (AT-MSCs). Methods: 6 adult racing horses treated for articular Injury but otherwise healthy. Methods: AT-MSCs were Isolated from horses and expanded In Dulbecco modified Eagle medium enriched with fetal bovine serum and antimicrobials. Expression of cell surface antigens and telomere length were Investigated via flow cytometry Differentiation of MSCs Into chondrocytes, osteoblasts, and adipocytes was Induced In vitro by specific stimuli...
Naskou MC, Sumner SM, Chocallo A, Kemelmakher H, Thoresen M, Copland I, Galipeau J, Peroni JF.Mesenchymal stem cells (MSCs) produced for clinical purposes rely on culture media containing fetal bovine serum (FBS) which is xenogeneic and has the potential to significantly alter the MSC phenotype, rendering these cells immunogenic. As a result of bovine-derived exogenous proteins expressed on the cell surface, MSCs may be recognized by the host immune system as non-self and be rejected. Platelet lysate (PL) may obviate some of these concerns and shows promising results in human medicine as a possible alternative to FBS. Our goal was to evaluate the use of equine platelet lysate (ePL) poo...
Marędziak M, Marycz K, Smieszek A, Lewandowski D, Toker NY.The aim of this study was to evaluate the proliferation rate and morphological changes of adipose-derived mesenchymal stem cells of canine and equine origin (Eq- and CaAdMSC). Investigated cells were exposed to a static magnetic field (MF) with the intensity of 0.5 T. Proliferation activity of cells was determined with the Alamar Blue assay. Obtained results, normalized in respect to the control culture, showed that EqAdMSC exposed to MF maintained a high proliferation status, whereas proliferation activity of CaAdMSC cultured in the presence of MF was decreased. Estimations of population doub...
Mensing N, Gasse H, Hambruch N, Haeger JD, Pfarrer C, Staszyk C.The equine periodontium provides tooth support and lifelong tooth eruption on a remarkable scale. These functions require continuous tissue remodeling. It is assumed that multipotent mesenchymal stromal cells (MSC) reside in the periodontal ligament (PDL) and play a crucial role in regulating physiological periodontal tissue regeneration. The aim of this study was to isolate and characterize equine periodontal MSC. Tissue samples were obtained from four healthy horses. Primary cell populations were harvested and cultured from the gingiva, from three horizontal levels of the PDL (apical, midtoo...
Marx C, Silveira MD, Beyer Nardi N.Mesenchymal stem cells, considered one of the most promising cell types for therapeutic applications due to their capacity to secrete regenerative bioactive molecules, are present in all tissues. Stem cells derived from the adipose tissue have been increasingly used for cell therapy in humans and animals, both as freshly isolated, stromal vascular fraction (SVF) cells, or as cultivated adipose-derived stem cells (ASCs). ASCs have been characterized in different animal species for proliferation, differentiation potential, immunophenotype, gene expression, and potential for tissue engineering. W...
Mancini IAD, Schmidt S, Brommer H, Pouran B, Schäfer S, Tessmar J, Mensinga A, van Rijen MHP, Groll J, Blunk T, Levato R, Malda J, van Weeren PR.Recent research has been focusing on the generation of living personalized osteochondral constructs for joint repair. Native articular cartilage has a zonal structure, which is not reflected in current constructs and which may be a cause of the frequent failure of these repair attempts. Therefore, we investigated the performance of a composite implant that further reflects the zonal distribution of cellular component both in vitro and in vivo in a long-term equine model. Constructs constituted of a 3D-printed poly(ϵ-caprolactone) (PCL) bone anchor from which reinforcing fibers protruded into ...
Reed SA, Johnson SE.Mesenchymal stem cells (MSCs) offer promise as therapeutic aids in the repair of tendon, ligament, and bone damage suffered by sport horses. The objective of the study was to identify and characterize stem-like cells from newborn foal umbilical cord blood (UCB). UCB was collected and MSC isolated using human reagents. The cells exhibit a fibroblast-like morphology and express the stem cell markers Oct4, SSEA-1, Tra1-60 and Tra1-81. Culture of the cells in tissue-specific differentiation media leads to the formation of cell types characteristic of mesodermal and endodermal origins. Chondrogenic...
Delco ML, Goodale M, Talts JF, Pownder SL, Koff MF, Miller AD, Nixon B, Bonassar LJ, Lundgren-Åkerlund E, Fortier LA.Early intervention with mesenchymal stem cells (MSCs) after articular trauma has the potential to limit progression of focal lesions and prevent ongoing cartilage degeneration by modulating the joint environment and/or contributing to repair. Integrin α10β1 is the main collagen type II binding receptor on chondrocytes, and MSCs that are selected for high expression of the α10 subunit have improved chondrogenic potential. The ability of α10β1-selected (integrin α10high) MSCs to protect cartilage after injury has not been investigated. To investigate integrin α10high MSCs to prevent postt...
Broeckx S, Suls M, Beerts C, Vandenberghe A, Seys B, Wuertz-Kozak K, Duchateau L, Spaas JH.Cell-based therapies, such as treatments with mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) are thought to have beneficial effects on the clinical outcome of orthopedic injuries, but very few animal studies with large sample size are published so far. Therefore, the aim of this study was to assess the safety and report the clinical outcome of allogenic, immature or chondrogenic induced MSCs in combination with PRP for the treatment of degenerative joint disease (DJD) in 165 horses. MSCs and PRP were isolated from a 6-year-old donor horse and transplanted either in their native s...
Müller M, Raabe O, Addicks K, Wenisch S, Arnhold S.In equine medicine, stem cell therapies for orthopaedic diseases are routinely accompanied by application of NSAIDs (non-steroidal anti-inflammatory drugs). Thus, it has to be analysed how NSAIDs actually affect the growth and differentiation potential of MSCs (mesenchymal stem cells) in vitro in order to predict the influence of NSAIDs such as phenylbutazone, meloxicam, celecoxib and flunixin on MSCs after grafting in vivo. The effects of NSAIDs were evaluated regarding cell viability and proliferation. Additionally, the multilineage differentiation capacity and cell migration was analysed. N...
Youngstrom DW, Barrett JG, Jose RR, Kaplan DL.Natural extracellular matrix provides a number of distinct advantages for engineering replacement orthopedic tissue due to its intrinsic functional properties. The goal of this study was to optimize a biologically derived scaffold for tendon tissue engineering using equine flexor digitorum superficialis tendons. We investigated changes in scaffold composition and ultrastructure in response to several mechanical, detergent and enzymatic decellularization protocols using microscopic techniques and a panel of biochemical assays to evaluate total protein, collagen, glycosaminoglycan, and deoxyribo...
Cortés-Araya Y, Amilon K, Rink BE, Black G, Lisowski Z, Donadeu FX, Esteves CL.Equine mesenchymal stem/stromal cells (MSCs) are multipotent cells that are widely used for treatment of musculoskeletal injuries, and there is significant interest in expanding their application to nonorthopedic conditions. MSCs possess antibacterial and immunomodulatory properties that may be relevant for combating infection; however, comparative studies using MSCs from different origins have not been carried out in the horse, and this was the focus of this study. Our results showed that MSC-conditioned media attenuated the growth of Escherichia coli, and that this effect was, on average, mo...
Frisbie DD, Smith RK.Stem cells have received much attention in recent times because of their potential to improve healing of othropaedic problems. This manuscript presents the genesis, issues and current state of stem cell treatment in equine medicine. Current literature supports the use of mesenchymal stem cells (MSCs) for treatment of orthopaedic problems.
Williams IF, Heaton A, McCullagh KG.The histological appearance of cells and tissues in the reparative scar tissue which forms in the equine superficial flexor tendon following partial rupture was compared to that of normal tendon. The repair fibroblasts were found to be larger and more basophilic than the tenocytes of normal tendon, to have large vesicular nuclei and to resemble the 'myofibroblasts' described in scar tissue elsewhere. The cell to matrix ratio in scarred zones of tendon was found to be increased and the concentration of collagen in these areas was less than in normal tendon. However, the scar tissue collagen was...
Mesenchymal stem cells (MSCs) offer promise as therapeutic aids in the repair of tendon and ligament disorders in sport horses. Equine allogeneic MSCs derived from umbilical cord blood (eUCB-MSCs) can be obtained in a minimally invasive fashion with successful propagation of MSCs. Objective: The objective of this study was to determine the applicability and therapeutic effect of eUCB-MSCs on tendinitis of the superficial digital flexor tendon, desmitis of the suspensory ligament, tendinitis of the deep digital flexor tendon, and desmitis of the inferior check ligament in clinical cases. Method...
