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.
Sharma R, Livesey MR, Wyllie DJ, Proudfoot C, Whitelaw CB, Hay DC, Donadeu FX.Pluripotent stem cells (PSCs) offer unprecedented biomedical potential not only in relation to humans but also companion animals, particularly the horse. Despite this, attempts to generate bona fide equine embryonic stem cells have been unsuccessful. A very limited number of induced PSC lines have so far been generated from equine fibroblasts but their potential for directed differentiation into clinically relevant tissues has not been explored. In this study, we used retroviral vectors to generate induced pluripotent stem cells (iPSCs) with comparatively high efficiency from equine keratinocy...
Gulati BR, Kumar R, Mohanty N, Kumar P, Somasundaram RK, Yadav PS.Tendon injuries are common in race horses, and mesenchymal stem cells (MSCs) isolated from adult and foetal tissue have been used for tendon regeneration. In the present study, we evaluated equine amniotic fluid (AF) as a source of MSCs and standardised methodology and markers for their in vitro tenogenic differentiation. Plastic-adherent colonies were isolated from 12 of 20 AF samples by day 6 after seeding and 70-80% cell confluency was reached by day 17. These cells expressed mesenchymal surface markers [cluster of differentiation (CD)73, CD90 and CD105] by reverse transcription (RT)-polyme...
Grevemeyer B, Bogdanovic L, Canton S, St Jean G, Cercone M, Ducharme NG, Brown BN.Airway obstruction is a common cause of poor performance in horses. Structural abnormalities (insufficient length, rigidity) can be a cause for the obstruction. Currently, there are a few effective clinical options for reconstruction of the equine larynx. A regenerative medicine approach to reconstruction may provide the capability to stabilize laryngeal structures and to encourage restoration of site-appropriate, functional, and host-derived tissue. The purpose of this study was the histopathological evaluation of (1) decellularization of equine (horse) laryngeal cartilages (epiglottis and ar...
Cadby JA, Buehler E, Godbout C, van Weeren PR, Snedeker JG.The role of intrinsic and extrinsic healing in injured tendons is still debated. In this study, we characterized cell plasticity, proliferative capacity, and migration characteristics as proxy measures of healing potential in cells derived from the peritenon (extrinsic healing) and compared these to cells from the tendon core (intrinsic healing). Both cell populations were extracted from horse superficial digital flexor tendon and characterized for tenogenic and matrix remodeling markers as well as for rates of migration and replication. Furthermore, colony-forming unit assays, multipotency as...
Carrade Holt DD, Wood JA, Granick JL, Walker NJ, Clark KC, Borjesson DL.Mesenchymal stem cells (MSCs) are used in both human clinical trials and veterinary medicine for the treatment of inflammatory and immune-mediated diseases. MSCs modulate inflammation by decreasing the cells and products of the inflammatory response. Stimulated equine MSCs from bone marrow (BM), adipose tissue (AT), cord blood (CB), and umbilical cord tissue (CT) inhibit lymphocyte proliferation and decrease inflammatory cytokine production. We hypothesized that equine MSCs inhibit T cell proliferation through secreted mediators and that MSCs from different tissue sources decrease T cell proli...
Gabrielyan A, Knaak S, Gelinsky M, Arnhold S, Rösen-Wolff A.In vivo tissue regeneration depends on migration of stem cells into injured areas, their differentiation into specific cell types, and their interaction with other cells that are necessary to generate new tissue. Human mesenchymal stem cells, a subset of bone marrow stromal cells (BMSCs), can migrate and differentiate into osteoblasts in bone tissue. This can be facilitated by recombinant growth factors and cytokines. In many animal species, the availability of genomic sequences, recombinant proteins, and/or antibodies is limited so that new approaches are needed to generate resources that fac...
Ferris RA, Frisbie DD, McCue PM.Current treatments for Persistent mating-induced endometritis such as uterine lavage and oxytocin therapy focus on aiding the uterus in removal of inflammatory products, but these treatments do not modulate the inciting inflammatory response. Biological treatments, such as autologous conditioned serum (ACS) and mesenchymal stem cells (MSCs), have been used in human and veterinary medicine for immunomodulation for over 10 years. The objectives of this project were to evaluate the ability of ACS or MSCs to modulate the inflammatory response to spermatozoa after breeding. Two experiments were pe...
Mercati F, Pascucci L, Curina G, Scocco P, Tardella FM, Dall'aglio C, Marini C, Ceccarelli P.The transplantation of multipotent mesenchymal stromal cells (MSCs) is a potentially promising therapy for the treatment of tendon and ligament injuries and some forms of articular pathology in horses. This study investigated the effects of storage conditions on MSCs. Equine adipose tissue-derived MSCs (eAd-MSCs) were stored at 4 °C and at room temperature (RT) for 24 and 48 h, and viability, doubling time, expression of CD44 and CD90 antigens, clonogenic/differentiation potentials, and karyotype were subsequently evaluated. The eAd-MSC viability was significantly affected by the storage ...
Barberini DJ, Freitas NP, Magnoni MS, Maia L, Listoni AJ, Heckler MC, Sudano MJ, Golim MA, da Cruz Landim-Alvarenga F, Amorim RM.Studies with mesenchymal stem cells (MSCs) are increasing due to their immunomodulatory, anti-inflammatory and tissue regenerative properties. However, there is still no agreement about the best source of equine MSCs for a bank for allogeneic therapy. The aim of this study was to evaluate the cell culture and immunophenotypic characteristics and differentiation potential of equine MSCs from bone marrow (BM-MSCs), adipose tissue (AT-MSCs) and umbilical cord (UC-MSCs) under identical in vitro conditions, to compare these sources for research or an allogeneic therapy cell bank. Methods: The BM-MS...
Broeckx S, Borena BM, Zimmerman M, Mariën T, Seys B, Suls M, Duchateau L, Spaas JH.It has been reported that mesenchymal stem cells (MSCs) have homing capacities and immunomodulating effects after an intravenous injection. However, transplanting MSCs in murine tail veins can result in pulmonary reactions and even death of the animals. Unfortunately, only a few intravenous MSC transplantations have been reported in large animal species and these were performed in a limited number of individuals. To assess the safety of MSC transplantations, a large study on 291 recipient horses is reported here. MSCs were isolated from the peripheral blood (PB) of a 4-year-old and 6-year-old ...
Broeckx SY, Maes S, Martinello T, Aerts D, Chiers K, Mariën T, Patruno M, Franco-Obregón A, Spaas JH.Besides the presence of somatic stem cells in hair follicles and dermis, the epidermis also contains a subpopulation of stem cells, reflecting its high regenerative capacity. However, only limited information concerning epidermis-derived epithelial-like stem/progenitor cells (EpSCs) is available to date. Nonetheless, this stem cell type could prove itself useful in skin reconstitution after injury. After harvesting from equine epidermis, the purified cells were characterized as EpSCs by means of positive expression for CD29, CD44, CD49f, CD90, Casein Kinase 2β, p63, and Ki67, low expression f...
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...
Schnabel LV, Pezzanite LM, Antczak DF, Felippe MJ, Fortier LA.The horse is a valuable species to assess the effect of allogeneic mesenchymal stromal cells (MSCs) in regenerative treatments. No studies to date have examined recipient response to major histocompatibility complex (MHC)-mismatched equine MSCs. The purposes of this study were to immunophenotype MSCs from horses of known MHC haplotype and to compare the immunogenicity of MSCs with differing MHC class II expression. Methods: MSCs and peripheral blood leukocytes (PBLs) were obtained from Thoroughbred horses (n=10) of known MHC haplotype (ELA-A2, -A3, and -A9 homozygotes). MSCs were cultured thro...
Broeckx S, Zimmerman M, Crocetti S, Suls M, Mariën T, Ferguson SJ, Chiers K, Duchateau L, Franco-Obregón A, Wuertz K, Spaas JH.Degenerative joint disease (DJD) is a major cause of reduced athletic function and retirement in equine performers. For this reason, regenerative therapies for DJD have gained increasing interest. Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) were isolated from a 6-year-old donor horse. MSCs were either used in their native state or after chondrogenic induction. In an initial study, 20 horses with naturally occurring DJD in the fetlock joint were divided in 4 groups and injected with the following: 1) PRP; 2) MSCs; 3) MSCs and PRP; or 4) chondrogenic induced MSCs and PRP. The ho...
Seo JP, Tsuzuki N, Haneda S, Yamada K, Furuoka H, Tabata Y, Sasaki N.Fracture is one of the most life-threatening injuries in horses. Fracture repair is often associated with unsatisfactory outcomes and is associated with a high incidence of complications. This study aimed to evaluate the osteogenic effects of gelatin/β-tricalcium phosphate (GT) sponges loaded with different concentrations/ratios of mesenchymal stem cells (MSCs) and bone morphogenetic protein-2 (BMP-2) in an equine bone defect model. Seven thoroughbred horses were used in this study. Eight bone defects were created in the third metatarsal bones of each horse. Then, eight treatments, namely con...
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...
Tongu EAO, Segabinazzi LGTM, Alvarenga ML, Monteiro A, Papa FO, Alvarenga MA.This study aimed to evaluate the effects of mesenchymal stem cell-conditioned medium (MSC-CM) on sperm parameters, intrauterine polymorphonuclear neutrophils (PMN), intrauterine fluid accumulation (IUF), and fertility in mares. In experiment 1, two ejaculates from ten stallions were extended to 50 million sperm/mL using a milk-based extender. Thereafter, 20 mL of extended semen was added of MSC-CM as follows: 0, 5, 10, 15, and 20 mL. Sperm kinetics and plasma membrane integrity were evaluated immediately after dilution (T0) and 2 h post-incubation at 37 °C (T2). In experiment 2, mares cha...
Abd-El-Aziz A, Riveroll A, Esparza-Gonsalez B, McD￮ L, Cohen AM, Fenech AL, Montelpare WJ.The aim of this research was to determine the impact of heat stress on cell differentiation in an equine mesenchymal stem cell model (EMSC) through the application of heat stress to primary EMSCs as they progressed through the cell specialization process. A proteomic analysis was performed using mass spectrometry to compare relative protein abundances among the proteomes of three cell types: progenitor EMSCs and differentiated osteoblasts and adipocytes, maintained at 37 °C and 42 °C during the process of cell differentiation. A cell-type and temperature-specific response to heat stress was ...
Chen Y, Caporali E, Stewart M.Bone morphogenetic protein 2 (BMP-2) is critical for skeletal and cartilage development, homeostasis and repair. This study was conducted to clone and characterize equine BMP-2, develop expression constructs for equine BMP-2, and to determine whether BMP-2 can stimulate chondrogenesis of equine synovial membrane-derived progenitor cells (SMPC). Methods: Equine BMP-2 cDNA was amplified from chondrocyte RNA, and then transferred into an expression plasmid and adenoviral vector. Effective expression of equine BMP-2 was confirmed using a BMP reporter cell line. SMPC were isolated from synovium, ex...
Edmonds RE, Garvican ER, Smith RK, Dudhia J.To provide evidence to support recommendations regarding the co-administration of drugs with mesenchymal stem cell (MSC) therapy. Objective: To determine the influence of sedatives, local anaesthetic and corticosteroids on MSC viability and proliferation, in comparison to somatic cells derived from tendon (TDCs). Methods: In vitro cell culture. Methods: MSCs (n = 3) and TDCs (n = 2) were cultured in media containing a clinically relevant dose range of xylazine, romifidine, detomidine and butorphanol, mepivacaine, methylprednisolone, or triamcinolone acetonide. Cell viability in suspension cult...
Narinx F, Sauvage A, Ceusters J, Grulke S, Serteyn D, Monclin S.To establish the safety of subconjunctival injections of autologous muscle-derived mesenchymal stem cells (mdMSCs) in healthy horses and to evaluate their effect in four horses (six eyes) with severe chronic equine immune-mediated keratitis (IMMK) that was unresponsive to medical treatments. Methods: MdMSCs were cultured from minimally invasive muscle biopsies. In the safety group, four healthy horses received two subconjunctival injections of 2.5 and 5 million cells, respectively, at 1-month interval, to the same eye. Ocular side effects were monitored for 1 month following each injection. ...
Carlier S, Depuydt E, Van Hecke L, Martens A, Saunders J, Spaas JH.Mesenchymal stem cells provide a valuable treatment option in orthopedic injuries in horses. Unassigned: The aim of this study was to evaluate the hematological, biochemical, immunological and immunomodulatory parameters following intralesional treatment with tenogenic primed equine allogeneic peripheral blood-derived mesenchymal stem cells (tpMSCs) in client-owned horses with naturally occurring superficial digital flexor tendon (SDFT) and suspensory ligament (SL) injuries. Unassigned: The immunogenicity and immunomodulatory capacities of tpMSCs were assessed in a modified mixed lymphocyte re...
Liu Y, Du M, Li X, Zhang L, Zhao B, Wang N, Dugarjaviin M.This study aimed to investigate differences in testicular tissue morphology, gene expression, and marker genes between sexually immature (1-year-old) and sexually mature (10-year-old) Mongolian horses. The purposes of our research were to provide insights into the reproductive physiology of male Mongolian horses and to identify potential markers for sexual maturity. The methods we applied included the transcriptomic profiling of testicular cells using single-cell sequencing techniques. Our results revealed significant differences in tissue morphology and gene expression patterns between the tw...
Del Prete C, Montano C, Cocchia N, de Chiara M, Gasparrini B, Pasolini MP.Defining the optimal therapy for endometritis remains a significant challenge for clinicians. Given the public health threat posed by antibiotic resistance and the inconclusiveness of traditional therapies, regenerative medicine has been proposed as an alternative. The objective of this study was to conduct a comprehensive systematic review and meta-analysis, to investigate the efficacy of regenerative medicine products in the treatment of both post-breeding persistent and chronic degenerative endometritis (PBIE/CDE) in mares, following the PRISMA guidelines. This research could be a comprehen...
Carmona JU, López C.(1) Background: Tendon and ligament injuries are a leading cause of lameness in horses, with significant economic implications. Platelet-rich plasma (PRP) has gained attention for its regenerative potential, but its efficacy remains uncertain due to inconsistent study designs and reporting. (2) Methods: This systematic review, following the PRISMA guidelines, evaluated 22 studies (clinical and experimental) to assess the safety and efficacy of PRP in treating equine tendon and ligament injuries. The risk of bias was analyzed using the ROBINS-I and RoB 2.0 tools. (3) Results: PRP demonstrated a...
Golonka P, Szklarz M, Kusz M, Marędziak M, Irwin Houston JM, Marycz K.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 ...
Clegg PD, Pinchbeck GL.Evidence-based medicine (EBM) refers to the conscientious, explicit, and judicious use of current best evidence from research for the care of an individual patient. Central to the adoption of EBM is both producing and identifying the best possible evidence for a particular intervention or therapy. This article identifies and reviews the approaches to producing and identifying the best possible evidence that is necessary for the full acceptance of stem cell therapies in the horse and reviews the approaches that will allow future clinical studies in stem cell therapies to provide the best eviden...
Tyrnenopoulou P, Karayannopoulou M, Angelopoulou S, Pyrros A, Mparous E, Koliakos G, Diakakis N.Carpal chip fractures are common causes of lameness in racehorses. Due to disadvantages in surgical management, adjuvant treatment modalities are usually necessary. Adipose-derived stem cells (ADSCs) have the potential to differentiate into other cell types including bone and cartilage cells. Adipose-derived stromal vascular fraction (SVF) is produced during ADSCs isolation from adipose tissue. The purpose of this report was to present the successful management of a grade III chip fracture in the right carpus of a 5-year-old Thoroughbred gelding by intra-articularly injected autologous SVF one...
Klymiuk MC, Speer J, Marco I, Elashry MI, Heimann M, Wenisch S, Arnhold S.Osteoarthritis (OA) is a common and incurable disease in humans and animals. To gain a better understanding of the pathogenesis and identify potential treatments, miRNAs will be extracted and analysed from extracellular vesicles (EVs) of equine adipose derived mesenchymal stem cells (AdMSCs). Methods: For this purpose we cultivated and pretreated AdMSCs under different conditions: interleukin 1β, shock wave, chondrogenic differentiation, chondrogenic differentiation under hypoxia, or after senescence. After treatment, EVs were harvested from the cell culture supernatants. Next-generation sequ...
Kornicka K, Geburek F, Röcken M, Marycz K.With this Editorial, we introduce the Special Issue "Adipose-Derived Stem Cells and Their Extracellular Microvesicles (ExMVs) for Tissue Engineering and Regenerative Medicine Applications" to the scientific community. In this issue, we focus on regenerative medicine, stem cells, and their clinical application.
Dahlgren LA.Wound management in horses can strike fear in some and passion in others. Wounds are common injuries in horses of all descriptions and requires exceptional knowledge and care to achieve a successful outcome. New treatments to overcome the critical challenges with equine wounds are always desired: managing dehisced and/or nonhealing wounds, managing exuberant granulation tissue, and ultimately achieving a functional tissue coverage. Regenerative medicine represents a broad set of tools with great promise to manipulate the deficiencies recognized in equine wound healing and improve the outcome.
Hagen A, Niebert S, Brandt VP, Holland H, Melzer M, Wehrend A, Burk J.Successful translation of multipotent mesenchymal stromal cell (MSC)-based therapies into clinical reality relies on adequate cell production procedures. These should be available not only for human MSC, but also for MSC from animal species relevant to preclinical research and veterinary medicine. The cell culture medium supplementation is one of the critical aspects in MSC production. Therefore, we previously established a scalable protocol for the production of buffy-coat based equine platelet lysate (ePL). This ePL proved to be a suitable alternative to fetal bovine serum (FBS) for equine a...
Marycz K, Bourebaba N, Serwotka-Suszczak A, Mularczyk M, Galuppo L, Bourebaba L.Equine metabolic syndrome (EMS) is recognized as one of the leading cause of health threatening in veterinary medicine worldwide. Recently, PTP1B inhibition has been proposed as an interesting strategy for liver insulin resistance reversion in both equines and humans, however as being a multifactorial disease, proper management of EMS horses further necessities additional interventional approaches aiming at repairing and restoring liver functions. In this study, we hypothesized that in vitro induction of Eq_ASCs hepatogenic differentiation will generate a specialized liver progenitor-like cell...
Radtke CL, Nino-Fong R, Esparza Gonzalez BP, McD￮ LA.The objective of this study was to validate non-equilibrium gravitational field-flow fractionation (GrFFF), an immunotag-less method of sorting mesenchymal stem cells (MSCs) into subpopulations, for use with MSCs derived from equine muscle tissue, periosteal tissue, bone marrow, and adipose tissue. Cells were collected from 6 young, adult horses, postmortem. 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 left supragluteal subcutaneous adipose tissue. Al...
Vackova I, Czernekova V, Tomanek M, Navratil J, Mosko T, Novakova Z.This study aimed to determine whether maternal cell contamination exists in cells derived from equine umbilical cord tissue, a perspective material for cell-based therapies in veterinary medicine. Potential maternal cell contamination was analyzed at DNA level via a set of 16 microsatellite markers in cells originating from the cord tissue of 22 foals. In these cells no maternal cell contamination was detected at a sensitivity level of 0.01%. Our results suggest that equine umbilical cord tissue-derived cells are entirely of fetal origin.
Fortier LA, Goodrich LR, Ribitsch I, Schnabel LV, Shepard DO, Van de Walle GR, Watts AE, Whealands Smith RK.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...
Spaas JH, Gomiero C, Broeckx SY, Van Hecke L, Maccatrozzo L, Martens A, Martinello T, Patruno M.Several cytokines and growth factors play an essential role in skin regeneration and epithelial-like stem cells (EpSCs) have beneficial effects on wound healing in horses. However, there are no reports available on the expression of these growth factors and cytokines after EpSC therapy. Methods: Wounds of 6 cm(2) were induced in the gluteus region of 6 horses and treated with (i) autologous EpSCs, (ii) allogeneic EpSCs, (iii) vehicle treatment or (iv) untreated control. Real time polymerase chain reaction was performed on tissue biopsies taken 1 and 5 weeks after these treatments to evaluate...
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...
Kisiday JD, Colbath AC, Tangtrongsup S.Ex vivo induction of chondrogenesis is a promising approach to improve upon the use of bone marrow mesenchymal stem cells (MSCs) for cartilage tissue engineering. This study evaluated the potential to induce chondrogenesis with days of culture in chondrogenic medium for MSCs encapsulated in self-assembling peptide hydrogel. To simulate the transition from preconditioning culture to implantation, MSCs were isolated from self-assembling peptide hydrogel into an individual cell suspension. Commitment to chondrogenesis was evaluated by seeding preconditioned MSCs into agarose and culturing in the ...
Mesoangioblasts (MABs) are vessel-associated stem cells that express pericyte markers and are originally isolated from the embryonic dorsal aorta. From postnatal small vessels of skeletal muscle and heart, it is possible to isolate cells with similar characteristics to embryonic MABs. Adult MABs have the capacity to self-renew and to differentiate into cell types of mesodermal lineages upon proper culture conditions. To date, the origin of MABs and the relationship with other muscle stem cells are still debated. Recently, in a phase I-II clinical trial, intra-arterial HLA-matched MABs were pro...
Stewart AS, Schaaf CR, Veerasammy B, Freund JM, Gonzalez LM.Equine intestinal epithelial stem cells (ISCs) serve as potential targets to treat horses with severe intestinal injury. The ability to isolate and store ISCs from intestinal biopsies creates an opportunity for both in vitro experiments to study ISC dynamics in a variety of intestinal diseases, and, in the future, utilize these cells as a possible therapy. If biopsies could be successfully stored prior to processing for ISCs, this would increase the availability of sample repositories for future experimental and therapeutic use. However, delayed culture of equine ISCs following prolonged sampl...
Williams LB, Russell KA, Koenig JB, Koch TG.Recently, equine multipotent mesenchymal stromal cells (MSC) have received significant attention as therapy for various conditions due to their proposed regenerative and immune-modulating capacity. MSC are commonly administered to the patient through a hypodermic needle. Currently, little information is available on the effect of such injection has on equine MSC immediate and delayed viability. We hypothesize that viability of equine MSC is not correlated with needle diameter during aspiration and injection. Results: Using a 3 mL syringe, manual injection of equine cord blood (CB) or bone ma...
Schröck C, Eydt C, Geburek F, Kaiser L, Päbst F, Burk J, Pfarrer C, Staszyk C.Allogeneic equine multipotent mesenchymal stromal cells (eMSCs) have been proposed for use in regenerative therapies in veterinary medicine. A source of allogeneic eMSCs might be the bone marrow from euthanized horses. The purpose of this study was to compare characteristics of equine bone marrow derived eMSC (eBM-MSCs) from euthanized horses (eut-MSCs) and from narcotized horses (nar-MSCs). Eut-MSCs and nar-MSCs showed typical eMSC marker profiles (positive: CD44, CD90; negative: CD11a/CD18 and MHCII) and possessed tri-lineage differentiation characteristics. Although CD105 and MHCI expressi...
Stewart MC.This article focuses on current issues facing cell-based therapies in equine practice and future studies validating the use of stem cells and related biologic therapies for the treatment of musculoskeletal conditions in the horse. Issues raised include the characterization and use of tissue- and anatomic location-specific mesenchymal stem cell (MSC) sources, the putative advantages and feasibility of allogeneic embryonic stem cell and MSC products, the technical advantages and performance of cell-based biologic agents that do not require extensive ex vivo manipulation, the regulation of MSC ho...
