Stem cells in horses refer to undifferentiated cells capable of self-renewal and differentiation into specialized cell types. These cells are primarily utilized in regenerative medicine and therapeutic applications to repair or replace damaged tissues in equine patients. Common sources of stem cells in horses include bone marrow, adipose tissue, and umbilical cord blood. Research in equine stem cell therapy focuses on understanding their potential to treat musculoskeletal injuries, such as tendon and ligament damage, and exploring their mechanisms of action. This page compiles peer-reviewed research studies and scholarly articles that examine the isolation, characterization, and therapeutic applications of stem cells in equine medicine.
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...
De Schauwer C, Goossens K, Piepers S, Hoogewijs MK, Govaere JL, Smits K, Meyer E, Van Soom A, Van de Walle GR.Mesenchymal stromal cells (MSCs) have been extensively studied for their promising capabilities in regenerative medicine. Although bone marrow is the best-known source for isolating equine MSCs, non-invasive alternative sources such as umbilical cord blood (UCB), umbilical cord matrix (UCM), and peripheral blood (PB) have also been reported. Methods: Equine MSCs from three non-invasive alternative sources were isolated from six individual mares (PB) and their foals (UCB and UCM) at parturition. To minimize inter-horse variability, the samples from the three sources were matched within the same...
Mohanty N, Gulati BR, Kumar R, Gera S, Kumar P, Somasundaram RK, Kumar S.Mesenchymal stem cells (MSCs) isolated from umbilical cord blood (UCB) in equines have not been well characterized with respect to the expression of pluripotency and mesenchymal markers and for tenogenic differentiation potential in vitro. The plastic adherent fibroblast-like cells isolated from 13 out of 20 UCB samples could proliferate till passage 20. The cells expressed pluripotency markers (OCT4, NANOG, and SOX2) and MSC surface markers (CD90, CD73, and CD105) by RT-PCR, but did not express CD34, CD45, and CD14. On immunocytochemistry, the isolated cells showed expression of CD90 and CD73...
Wu H, Han D, Jiang Z, Zhao D, Liu M, Xu X, Liu X, Yang L, Ji X, Wang M, Zhang S.B cell activating factor (BAFF) and its receptors were regarded as elements of the immune system, regulating the fate of B cell. In recent years, these molecules were identified in a number of normal and pathological tissues, expanding their potential functions beyond the immune system. In this study, on the basis of molecular clone and prokaryotic expression of equine BAFF, we reported that equine adipose-derived stem cell (ASC) expressed BAFF and its receptors, which exhibited the increased expression during ASC adipogenic differentiation in vitro. Moreover, with the addition of recombinant ...
Carvalho AM, Yamada AL, Golim MA, Álvarez LE, Hussni CA, Alves AL.Mesenchymal stem cells (MSCs) have been used to treat equine tendonitis with promising results; however, little is known about the potential migration of these cells. Objective: To assess the possible migration of MSCs from an implantation site in the superficial digital flexor tendon (SDFT) to a lesion in the SDFT of the contralateral limb. Methods: In vivo experimental study. Methods: Adipose-derived MSCs were isolated from 4 healthy horses. Lesions were induced in the SDFTs of both forelimbs, followed by intralesional implantation of autologous adipose-derived MSCs labelled with nanocrystal...
Carter-Arnold JL, Neilsen NL, Amelse LL, Odoi A, Dhar MS.Stem cell therapies are used routinely in equine practice. Most published reports characterise stem cells derived from younger horses; however, middle-aged horses are often in athletic performance, and experience degenerative medical conditions. Thus, mesenchymal stem cells (MSCs) from this group should be investigated. Objective: To describe differences in in vitro adherence, proliferation and potential for differentiation of equine bone marrow-derived MSCs (equine BMMSCs) harvested from middle-aged (10-13 years old) female donors. Methods: Descriptive study of stem cell characteristics. Meth...
Castro FO, Torres A, Cabezas J, Rodríguez-Alvarez L.Repair of injured soft and hard tissues in horses can benefit greatly from the use of regenerative therapies with mesenchymal stem cells (MSC). Vitamin-C and platelet-rich-plasma had been used for in vitro differentiation of MSC. This study was aimed to evaluate the effect of vitamin-C, platelet-rich-plasma and their combination on the in vitro differentiation of adipose horse MSC. We isolated MSC from horse fat and differentiated them in vitro into osteogenic and chondrogenic lineages, as demonstrated by specific staining and RT-qPCR of selected genes. Combining vitamin-C and plasma-rich-plat...
Jülke H, Veit C, Ribitsch I, Brehm W, Ludewig E, Delling U.The purpose of this study was to evaluate the use of three different superparamagnetic iron oxide (SPIO) particles for labeling of ovine and equine bone marrow (BM)-derived multipotent stromal cells (MSCs) in vitro. MSCs were obtained from five adult sheep and horses, respectively. After three passages (p3), cells were labeled with either 1) Molday ION Rhodamine B, 2) Endorem, 3) Resovist, or 4) remained unlabeled as control. Labeling efficiency, marker retention, and long-term detectability in MRI until p7 were evaluated. Further, proliferation capacity and trilineage differentiation as indic...
McD￮ LA, Esparza Gonzalez BP, Nino-Fong R, Aburto E.Autologous mesenchymal stem cells (MSCs) have been used as a potential cell-based therapy in various animal and human diseases. Their differentiation capacity makes them useful as a novel strategy in the treatment of tissue injury in which the healing process is compromised or delayed. In horses, bone healing is slow, taking a minimum of 6-12 months. The osteogenic capacity of equine bone marrow and muscle MSCs mixed with fibrin glue or phosphate-buffered saline (PBS) as a scaffold is assessed. Bone production by the following groups was compared: Group 1, bone marrow (BM) MSCs in fibrin glue;...
Patruno M, Martinello T.In order to treat frequently occurring conditions such as traumatic rupture or over-strain tendinopathies, the techniques of tissue engineering and cell-based therapies have become an accepted modus operandi since other available remedies appear to be ineffective in restoring the original structure and function of the injured tissue. However, the mechanisms accounting for the effectiveness of novel regenerative approaches in treating equine tendon and ligament injuries remain poorly characterised. In this review we summarize and discuss the most significant results of our research regarding bi...
Glynn ER, Londono AS, Zinn SA, Hoagland TA, Govoni KE.The use of equine bone marrow mesenchymal stem cells (BMSC) is a novel method to improve fracture healing in horses. However, additional research is needed to identify optimal culture conditions and to determine the mechanisms involved in regulating BMSC differentiation into osteoblasts. The objectives of the experiments were to determine: 1) if autologous or commercial serum is better for proliferation and differentiation of equine BMSC into osteoblasts, and 2) the expression of key transcription factors during the differentiation of equine BMSC into osteoblasts. Equine BMSC were isolated fro...
Tsuzuki N, Seo JP, Yamada K, Haneda S, Furuoka H, Tabata Y, Sasaki N.We evaluated the curative efficacy of a gelatin β-tricalcium phosphate (β-TCP) sponge loaded with mesenchymal stem cells (MSC), bone morphogenic protein-2 (BMP-2), and platelet-rich plasma (PRP) by insertion into an experimentally induced osteochondral defect. A hole of 10 mm diameter and depth was drilled in the bilateral medial femoral condyles of 7 thoroughbred horses, and into each either a loaded sponge (treatment) or a saline-infused β-TCP sponge (control) was inserted. After 16 weeks, defects were examined by computed tomography, macroscopic analyses, and histological analyses. The m...
Trela JM, Spriet M, Padgett KA, Galuppo LD, Vaughan B, Vidal MA.Intra-arterial (i.a.) and intravenous (i.v.) regional limb perfusions (RLP) through the median artery and cephalic vein, respectively, have been previously investigated for administration of mesenchymal stem cells (MSCs) to the equine distal limb. Limitations due to thrombosis of the arteries after i.a. RLP and poor distribution of MSCs to the foot with i.v. RLP were observed. These techniques need to be modified for clinical use. Objective: Evaluate the distribution, uptake and persistence of radiolabelled MSCs after i.a. injection through the median artery without a tourniquet and after i.v....
Tsuzuki N, Seo JP, Haneda S, Yamada K, Furuoka H, Tabata Y, Sasaki N.A 13-month-old Thoroughbred filly was diagnosed with osteochondritis dissecans (OCD) of the medial tibial malleolus. A sponge impregnated with platelet-rich plasma, bone morphogenetic protein-2, mesenchymal stem cells and gelatin β-tricalcium phosphate was applied to the OCD site following arthroscopy and debridement. Postoperative radiography (every week for 16 weeks), computed tomography (CT) (16 weeks postoperatively), arthroscopy (16 weeks postoperatively) and biopsy of the regenerated tissue (16 weeks postoperatively) were performed to evaluate the outcome. Radiographically, the defect b...
Pigott JH, Ishihara A, Wellman ML, Russell DS, Bertone AL.To compare the clinical and inflammatory joint responses to intra-articular injection of bone marrow-derived mesenchymal stem cells (MSC) including autologous, genetically modified autologous, allogeneic, or xenogeneic cells in horses. Methods: Six five-year-old Thoroughbred mares had one fetlock joint injected with Gey's balanced salt solution as the vehicle control. Each fetlock joint of each horse was subsequently injected with 15 million MSC from the described MSC groups, and were assessed for 28 days for clinical and inflammatory parameters representing synovitis, joint swelling, and pain...
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....
Ricco S, Renzi S, Del Bue M, Conti V, Merli E, Ramoni R, Lucarelli E, Gnudi G, Ferrari M, Grolli S.Overstrain tendonitis are common pathologies in the sport horses. Therapeutic approaches to tendon healing do not always result in a satisfactory anatomical and functional repair, and healed tendon is often characterized by functional impairment and high risk of reinjury. Recently, mesenchymal stem cells (MSCs) and platelet rich plasma (PRP) have been proposed as novel therapeutic treatments to improve the tendon repair process. MSCs are multipotent, easy to culture and being originated from adult donors do not pose ethical issues. To date, autologous MSCs have been investigated mainly in the ...
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 ...
Seo JP, Tanabe T, Tsuzuki N, Haneda S, Yamada K, Furuoka H, Tabata Y, Sasaki N.Osteochondrosis (OC) is a common and clinically important joint disorder in horses. However, repair of the OC region is difficult because of the avascular nature of cartilage. This study aimed to evaluate the efficacy of bilayer gelatin/β-tricalcium phosphate (GT) sponges loaded with mesenchymal stem cells (MSCs), chondrocytes, bone morphogenetic protein-2 (BMP-2), and platelet rich plasma (PRP) for the repair of osteochondral defects of the talus in horses. Full-thickness osteochondral defects were created on both the lateral trochlear ridges of the talus (n = 6). In the test group, a basic ...
Campos-Junior PH, Costa GM, de Avelar GF, Segatelli TM, Lacerda SM, Aponte PM, de França LR.Morphometry is a classical quantitative method often used in biology to provide a data basis for functional interpretations/interactions of a particular organ or system. Herein we took advantage of this valuable approach to evaluate the spermatogonial stem cell niche using the horse testis and immunocytochemical localization of GFRA1 [glial cell line-derived neurotrophic factor receptor produced by Sertoli cells)] as an example. Using the NIH ImageJ free software, we describe in detail all the necessary steps to investigate this specific and crucial microenvironment. Based on several recently ...
Lange-Consiglio A, Rossi D, Tassan S, Perego R, Cremonesi F, Parolini O.We have recently demonstrated that heterologous transplantation of horse amniotic membrane-derived mesenchymal cells (AMCs) can be useful for cell therapy applications in tendon diseases, and hypothesized that these cells may promote tendon repair via paracrine-acting molecules targeting inflammatory processes. To test this hypothesis, here we examined the immunomodulatory characteristics of AMCs and of their conditioned medium (AMC-CM) in vitro, and studied the potential therapeutic effect of AMC-CM in thirteen different spontaneous horse tendon and ligament injuries in vivo. Our results demo...
Carvalho Ade M, Badial PR, Álvarez LE, Yamada AL, Borges AS, Deffune E, Hussni CA, Garcia Alves AL.Tendon injury is a major cause of lameness and decreased performance in athletic equines. Various therapies for tendonitis have been described; however, none of these therapies results in complete tissue regeneration, and the injury recurrence rate is high even after long recovery periods involving rest and physiotherapy. Methods: A lesion was induced with collagenase gel in the superficial digital flexor tendon in the center portion of the metacarpal region of eight equines of mixed breed. After two weeks, the lesions of the animals in the treated and control groups were treated through the i...
Sivaguru M, Eichorst JP, Durgam S, Fried GA, Stewart AA, Stewart MC.Injuries and damage to tendons plague both human and equine athletes. At the site of injuries, various cells congregate to repair and re-structure the collagen. Treatments for collagen injury range from simple procedures such as icing and pharmaceutical treatments to more complex surgeries and the implantation of stem cells. Regardless of the treatment, the level of mechanical stimulation incurred by the recovering tendon is crucial. However, for a given tendon injury, it is not known precisely how much of a load should be applied for an effective recovery. Both too much and too little loading...
Kang JG, Park SB, Seo MS, Kim HS, Chae JS, Kang KS.Tendinitis of the superficial digital flexor tendon (SDFT) is a significant cause of lameness in horses; however, recent studies have shown that stem cells could be useful in veterinary regenerative medicine. Therefore, we isolated and characterized equine umbilical cord blood mesenchymal stem cells (eUCB-MSCs) from equine umbilical cord blood obtained from thoroughbred mares during the foaling period. Horses that had tendinitis of the SDFT were treated with eUCB-MSCs to confirm the therapeutic effect. After eUCB-MSCs transplantation, the core lesion in the SDFT was found to decrease. These re...
Hall V, Hinrichs K, Lazzari G, Betts DH, Hyttel P.Over many decades assisted reproductive technologies, including artificial insemination, embryo transfer, in vitro production (IVP) of embryos, cloning by somatic cell nuclear transfer (SCNT), and stem cell culture, have been developed with the aim of refining breeding strategies for improved production and health in animal husbandry. More recently, biomedical applications of these technologies, in particular, SCNT and stem cell culture, have been pursued in domestic mammals in order to create models for human disease and therapy. The following review focuses on presenting important aspects of...
Schnabel LV, Fortier LA, McIlwraith CW, Nobert KM.Stem cells are commonly used in equine practice to treat musculoskeletal disorders including tendonitis, osteoarthritis, and more recently laminitis. As the field of regenerative medicine continues to advance, equine practitioners need contemporary information regarding the choice of stem cell type and recommendations regarding clinical implementation of stem cell therapies. Clinicians must also be aware of the limitation in current knowledge regarding stem cells, and the impending regulatory laws that may limit the use of equine stem cells in clinical patients.
Ishihara A, Helbig HJ, Sanchez-Hodge RB, Wellman ML, Landrigan MD, Bertone AL.Objective-To determine the efficiency of a novel point-of-care gravitational marrow separator and bone marrow aspiration needle for concentrated bone marrow production and bone marrow-derived mesenchymal stem cell (MSC) separation and assess the effect of repeated bone marrow collections in horses. Animals-8 healthy adult horses. Procedures-Bone marrow aspiration was performed twice (1 month apart) from sternebral bodies with a standard or prototype multidirectional needle. Concentrated bone marrow was obtained by gravitational marrow separation and evaluated for WBC and platelet counts, autom...
Moriyama H, Kasashima Y, Kuwano A, Wada S.To identify morphologically the locations of equine corneal epithelial stem cells (CESCs) and to culture these cells. Methods: We studied the eyes of 12 adult thoroughbred horses. Methods: Eye tissues were immunostained for two positive stem cell markers (p63, CK14) and one negative marker (CK3) to identify the locations of CESCs, so we could compare their immunostaining patterns with those of human stem cells previously reported. We compared the proliferation rates and morphological features of epithelial cells isolated from the corneal limbus and central cornea. Results: Undifferentiated cel...
Dias MC, Landim-Alvarenga FD, de Moraes CN, da Costa LD, Geraldini CM, de Vasconcelos Machado VM, Maia L.Mesenchymal stromal cells (MSCs) have great therapeutic potential, particularly in the process of tissue repair and immunomodulation through the secretion of biomolecules. Thus, the aim of this study was to evaluate the hypothesis that intramuscular transplantation of allogeneic MSCs obtained from equine umbilical cord (UC-MSCs) is safe, demonstrating that this is a suitable source of stem cells for therapeutic use. Results: For this, UC-MSCs were cultured, characterized and cryopreserved for future transplantation in six healthy mares. On day 0, transplantation of three million UC-MSCs dilute...
Bernardino PN, Smith WA, Galuppo LD, Mur PE, Cassano JM.Mesenchymal stromal (stem) cells (MSCs) have been studied to treat many common orthopedic injuries in horses. However, there is limited information available on when and how to use this treatment effectively. The aim of this retrospective study is to report case features, treatment protocols, and clinical outcomes in horses treated with MSCs. Methods: 65 horses presenting with tendinous, ligamentous, and articular injuries, and treated with MSCs prepared by a single laboratory between 2016 and 2019. Outcome information was available for 26 horses. Methods: Signalment, clinical signs, diagnosti...
Desantis S, Accogli G, Crovace A, Francioso EG, Crovace AM.The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. Recent studies demonstrated that the glycans in the glycocalyx of MSCs are promising candidates as cell biomarkers. In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides an...
Emmerich IU.In 2019, one novel pharmaceutical agent for horses or food-producing animals was released on the German market: An injection suspension for horses containing chondrogenic-induced equine allogeneic peripheral blood-derived mesenchymal stem cells as the active ingredient (ArtiCell Forte) is now available. Two established veterinary active pharmaceutical ingredients became accessible for additional species: a salicylanilide anthelmintic oxyclozanide (Distocur) for the treatment and control of fascioliasis in sheep as well as a type-I synthetic pyrethroid permethrin (Z-Itch), which now has additio...
Kamineni S, Ruggles A, Ashfaq H.Ultrasonic debridement as a treatment for tendinopathy and desmitis is a relatively new approach in orthopedic surgery. Previously only used in limited cases, this procedure shows promise for treating ligament-bone and tendon-bone interface injuries. We present a case study of a 2-yr-old thoroughbred male horse, unable to train due to recalcitrant symptoms after extensive conservative management of suspensory branch desmitis. It was then treated with ultrasonic debridement and concurrent manubrial stem cell autograft injection, to treat the ultrasound visualized lesion. Post-surgically, the pa...
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....
Duddy HR, Schoonover MJ, Hague BA.Tendon and ligament injuries are significant causes of loss of use and early retirement in performance horses. Amniotic fluid and tissue are excellent sources of growth factors and cytokines important in tendon and ligament healing. Thus, an equine-origin liquid amnion allograft (ELAA) may be beneficial in the treatment of equine tendonitis and desmitis. Objectives of this study were to report the outcome achieved (i.e. ability to return to work) for horses diagnosed with tendonitis or desmitis lesions treated with local injection of ELAA and to compare these outcomes to those reported for oth...
Roth SP, Brehm W, Troillet A.Cell-based therapies for the treatment of osteoarthritis in equine patients experienced a real boom within the last few years. In every day medical practice, attending veterinary surgeons extract patient's blood or other autologous tissue samples and process the material for the purpose of administering the resulting product to the same patient under their own responsibility. Although being consistently classified as treatment option within the framework of regenerative medicine, the manufacturing processes, ingredients, and mechanisms of action remain highly diverse among cell-based therapies...
Yang Q, Lopez MJ.The equine hoof dermal-epidermal interface requires progenitor cells with distinct characteristics. This study was designed to provide accurate ultrastructural depictions of progenitor cells isolated from inflamed tissue and normal tissue before and after cryopreservation and following selection of cells expressing both keratin (K) 14 (ectodermal) and cluster of differentiation (CD) 105 (mesodermal). Passage 3 cell ultrastructure was assessed following 2D culture and after 3D culture on decellularized hoof tissue scaffolds. Outcome measures included light, transmission electron, and scanning e...
Oliveira Spila D, Maranhão RPA, Ocarino NM, de Lima JTB, Melo FG, Boeloni JN, Serakides R.The effects of two concentrations of triiodothyronine (T3; 0.01 and 1,000 nM) on the osteogenic and chondrogenic differentiation abilities of equine adipose-derived mesenchymal stem cells (AD-MSCs) were evaluated. The osteogenic study evaluated the effect of T3 using alkaline phosphatase activity (ALP) assay; cell viability and density; and formation of mineralized nodules at Days 7, 14, and 21 in culture. The chondrogenic study tested the effect of T3 through ALP assay, mitochondrial metabolism, cell density, and periodic acid-Schiff-positive (PAS+) matrix percentage at Days 7 and 14. In bot...
Melzer M, Burk J, Guest DJ, Dudhia J.Mesenchymal stromal cells (MSC) isolated form bone marrow and adipose tissue are the most common cells used for cell therapy of orthopedic diseases. MSC derived from different tissues show differences in terms of their proliferation, differentiation potential and viability in prolonged cell culture. This suggests that there may be subtle differences in intracellular signaling pathways that modulate these cellular characteristics. The Rho/ROCK signaling pathway is essential for many cellular functions. Targeting of this pathway by the ROCK inhibitor Y-27632 has been shown to be beneficial for c...
Maia L, Dias MC, de Moraes CN, de Paula Freitas-Dell'Aqua C, da Mota LS, Santiloni V, da Cruz Landim-Alvarenga F.Cryopreservation is a feasible alternative to maintaining several cell lines, particularly for immediate therapeutic use, transportation of samples, and implementation of new in vitro studies. This work parts from the hypothesis that the medium of cryopreservation composed by 90% of conditioned medium (CM) supports cryopreservation of equine umbilical cord intervascular matrix mesenchymal stem cells (UCIM-MSCs), allowing the maintenance of the biological properties for the establishment of cell banks intended for therapeutic use and in vitro studies. Thus, we evaluated the viability, apoptosis...
Owens SD, Burges J, Johns JL, Carrade DD, Galuppo LD, Librach F, Borjesson DL.The therapeutic use of bone marrow-derived mononuclear cells (MNCs) and mesenchymal stem cells for the treatment of soft tissue and orthopedic injuries in equine patients is expanding. After collection, bone marrow must be reduced in volume and depleted of RBCs for immediate therapeutic use or to prepare cells for culture or cryopreservation and storage. The MarrowXpress (MXP) System is an automated, closed, sterile system designed to process human bone marrow samples. Objective: The purpose of this study was to evaluate the capacity of the MXP System to process equine bone marrow to reduce vo...
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...
Santos VH, Pfeifer JPH, de Souza JB, Milani BHG, de Oliveira RA, Assis MG, Deffune E, Moroz A, Alves ALG.The original article [1] contained a minor error regarding the mean diameter of the alginate microcapsules described in relation to Fig. 4 in the Results section. The microcapsules had an actual mean diameter of 3000 μm instead of 1000 μm as mistakenly mentioned in the original article.
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...
Sandersen C, Ceusters J, Fourez A, Tosi I, Graide H, Lejeune JP, Serteyn D.Recurrent laryngeal neuropathy (RLN) commonly affects horses and is characterized by abnormal respiratory sounds and exercise intolerance. The recurrent laryngeal nerve shows lesions of demyelination. The benefit of applying stem cells to demyelinated nerves has been demonstrated in various animal models. The aim of the study was to test the feasibility and safety of a peri-neuronal injection of autologous muscle-derived mesenchymal stem cells to the left recurrent laryngeal nerve in healthy horses by using an electrical nerve stimulator. Muscle-derived stems cell are obtained from five health...
Karasiewicz J, Andrzej-Modlinski J.Our Department of Experimental Embryology originated from The Laboratory of Embryo Biotechnology, which was organized and directed by Dr. Maria Czlonkowska until her premature death in 1991. Proving successful international transfer of frozen equine embryos and generation of an embryonic sheep-goat chimaera surviving ten years were outstanding achievements of her term. In the 1990s, we produced advanced fetuses of mice after reconstructing enucleated oocytes with embryonic stem (ES) cells, as well as mice originating entirely from ES cells by substitution of the inner cell mass with ES cells. ...
Bastos FZ, Barussi FCM, Santi TF, Vieira BP, Senegaglia AC, Cruz FF, Michelotto PV.There is no consensus on aspects of equine bone marrow collection and processing. The study aimed to describe the collection of large volumes of bone marrow from horses of advanced age, with emphasis on bone marrow mononuclear cells (BMMCs) recovery and viability after cryopreservation. Fourteen horses, aged 3-24 years, were divided into three experiments. E1 studied the feasibility of collecting 200 mL from the sternums of horses of advanced age; E2 examined the number of cells obtained from the first and last syringe of each puncture; and E3 investigated the influence of heparin concentrati...
Horstmeier C, Ahrberg AB, Berner D, Burk J, Gittel C, Hillmann A, Offhaus J, Brehm W.The magic angle effect increases the MRI signal of healthy tendon tissue and could be used for more detailed evaluation of tendon structure. Furthermore, it could support the discrimination of hypointense artefacts induced by contrast agents such as superparamagnetic iron oxide used for cell tracking. However, magic angle MRI of the equine superficial digital flexor tendon has not been accomplished in vivo in standing low-field MRI so far. The aim of this in vivo study was to evaluate the practicability of this magic angle technique and its benefit for tracking superparamagnetic iron oxide-lab...
Supokawej A, Korchunjit W, Wongtawan T.The Wingless and Int-1 (WNT) and bone morphogenic protein/growth differentiation factor (BMP/GDF) signalling pathways contribute significantly to the development of the musculoskeletal system. The mechanism by which they contribute is as follows: BMP/GDF signalling usually promotes tendon differentiation, whereas WNT signalling inhibits it. We hypothesised that inhibiting WNT and subsequently stimulating BMP signalling may enhance the tenogenic differentiation of stem cells. The objective of this study was to determine whether a combination of WNT inhibitor (KY02111) and BMP12/GDF7 protein cou...
Pawlikowska-Warych M, Deptuła W.One of the most common reasons for horse lameness is subchondral bone cysts (SBCs), which are especially evident in young horse athletes. It is believed that SBC development is strongly associated with an individual's bone growth and/or bone microstructure impairment. Current methods of SBC treatment include pharmacological treatment or surgical procedures which may allow the bone within the cyst to rebuild and be restored to properly developed bone tissue. Thus, we propose filling the SBCs with a 3D complex of alginate hydrogel and autologous adipose derived mesenchymal stem cells (ASCs). We ...
Salami F, Ghodrati M, Parham A, Mehrzad J.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 ...
Soukup R, Gerner I, Gültekin S, Baik H, Oesterreicher J, Grillari J, Jenner F.Extracellular vesicles (EVs) are nanosized lipid bilayer-encapsulated particles secreted by virtually all cell types. EVs play an essential role in cellular crosstalk in health and disease. The cellular origin of EVs determines their composition and potential therapeutic effect. Mesenchymal stem/stromal cell (MSC)-derived EVs have shown a comparable therapeutic potential to their donor cells, making them a promising tool for regenerative medicine. The therapeutic application of EVs circumvents some safety concerns associated with the transplantation of viable, replicating cells and facilitates...
Ganiev I, Alexandrova N, Aimaletdinov A, Rutland C, Malanyeva A, Rizvanov A, Zakirova E.One of the major problems observed in veterinary practice is articular cartilage injuries in animals. In terms of agriculture, it leads to their culling from the herd, even if they are highly productive animals. With companion animals, owners usually have to decide between euthanasia or long-term sometimes lifelong treatment of the injury by a veterinarian. The use of mesenchymal stem cells (MSCs) for the treatment of cartilage injury in veterinary medicine is based on the good results observed in preclinical studies, where large animals have been used as experimental models to study the regen...
Mançanares ACF, Cabezas J, Manríquez J, de Oliveira VC, Wong Alvaro YS, Rojas D, Navarrete Aguirre F, Rodriguez-Alvarez L, Castro FO.In mesenchymal stem cells (MSCs), it has been reported that prostaglandin E2 (PGE2) stimulation of EP2 and EP4 receptors triggers processes such as migration, self-renewal, survival, and proliferation, and their activation is involved in homing. The aim of this work was to establish a genetically modified adipose (aMSC) model in which receptor genes EP2 and EP4 were edited separately using the CRISPR/Cas9 system. After edition, the genes were evaluated as to if the expression of MSC surface markers was affected, as well as the migration capacity in vitro of the generated cells. Adipose MSCs we...
Campos-Junior PH, Costa GM, de Avelar GF, Segatelli TM, Lacerda SM, Aponte PM, de França LR.Morphometry is a classical quantitative method often used in biology to provide a data basis for functional interpretations/interactions of a particular organ or system. Herein we took advantage of this valuable approach to evaluate the spermatogonial stem cell niche using the horse testis and immunocytochemical localization of GFRA1 [glial cell line-derived neurotrophic factor receptor produced by Sertoli cells)] as an example. Using the NIH ImageJ free software, we describe in detail all the necessary steps to investigate this specific and crucial microenvironment. Based on several recently ...
