Regenerative medicine in horses involves the use of biological therapies to repair or replace damaged tissues and organs. This field focuses on enhancing the body's natural healing processes through the application of stem cells, platelet-rich plasma (PRP), and other bioactive substances. These therapies aim to improve the recovery of musculoskeletal injuries, such as tendon and ligament damage, which are common in equine athletes. Research in regenerative medicine explores the mechanisms of tissue regeneration, the efficacy of different treatment modalities, and their application in clinical settings. This page aggregates peer-reviewed research studies and scholarly articles that investigate the methodologies, outcomes, and potential applications of regenerative medicine in equine veterinary practice.
Sasao T, Fukuda Y, Yoshida S, Miyabara S, Kasashima Y, Kuwano A, Arai K.In regenerative medicine using transplantation of mesenchymal stem cells (MSCs), the importance of regulating the quality of MSCs has been well recognized; however, there is little information concerning the relationship between the population doubling level (PDL) and the stemness of MSCs in equine medicine. In this study, we showed that the amount of glycosaminoglycan (GAG) secreted by bone marrow-derived MSCs (BMSCs) decreases with increase of PDL. Enzymatic digestion and two-dimensional electrophoresis revealed that a main component of GAG produced by BMSCs was hyaluronan with a small amoun...
Aguiar C, Therrien J, Lemire P, Segura M, Smith LC, Theoret CL.Skin trauma in horses often leads to the development of chronic nonhealing wounds that lack a keratinocyte cover, vital for healing. Reports in mouse and man confirm the possibility of generating functional keratinocytes from induced pluripotent stem cells (iPSC), thus presenting myriad potential applications for wound management or treatment of skin disease. Similarly, differentiation of equine iPSC (eiPSC) into a keratinocyte lineage should provide opportunities for the advancement of veterinary regenerative medicine. Objective: The purpose of this study was to develop an efficient method fo...
Linardi RL, Megee SO, Mainardi SR, Senoo M, Galantino-Homer HL.The limited characterization of equine skin, eye and hoof epithelial stem cell (ESC) and differentiation markers impedes the investigation of the physiology and pathophysiology of these tissues. Objective: To characterize ESC and differentiation marker expression in epithelial tissues of the equine eye, haired skin and hoof capsule. Methods: Indirect immunofluorescence microscopy and immunoblotting were used to detect expression and tissue localization of keratin (K) isoforms K3, K10, K14 and K124, the transcription factor p63 (a marker of ESCs) and phosphorylated p63 [pp63; a marker of ESC tr...
Aguiar C, Theoret C, Smith O, Segura M, Lemire P, Smith LC.Induced pluripotent stem cells (iPSC) have brought immense hope to cellular therapy and regenerative medicine. However, the antigenicity of iPSC has not been well documented and remains a hurdle for clinical applications. Expression of major histocompatibility complex (MHC) molecules by human and murine iPSC is downregulated, making these cells potentially safe for transplantation. No such data are available for any large animal model. Objective: To measure expression of MHC molecules on equine iPSC (eiPSC) and describe their antigenicity using intradermal testing. The hypothesis was that allo...
Gaspar D, Spanoudes K, Holladay C, Pandit A, Zeugolis D.The last decade has seen significant developments in cell therapies, based on permanently differentiated, reprogrammed or engineered stem cells, for tendon injuries and degenerative conditions. In vitro studies assess the influence of biophysical, biochemical and biological signals on tenogenic phenotype maintenance and/or differentiation towards tenogenic lineage. However, the ideal culture environment has yet to be identified due to the lack of standardised experimental setup and readout system. Bone marrow mesenchymal stem cells and tenocytes/dermal fibroblasts appear to be the cell populat...
Lomas AJ, Ryan CN, Sorushanova A, Shologu N, Sideri AI, Tsioli V, Fthenakis GC, Tzora A, Skoufos I, Quinlan LR, O'Laighin G, Mullen AM, Kelly JL....Tendon injuries represent a significant clinical burden on healthcare systems worldwide. As the human population ages and the life expectancy increases, tendon injuries will become more prevalent, especially among young individuals with long life ahead of them. Advancements in engineering, chemistry and biology have made available an array of three-dimensional scaffold-based intervention strategies, natural or synthetic in origin. Further, functionalisation strategies, based on biophysical, biochemical and biological cues, offer control over cellular functions; localisation and sustained relea...
Marędziak M, Marycz K, Lewandowski D, Siudzińska A, Śmieszek A.The aim of this work study was to evaluate the cytophysiological activity of equine adipose-derived stem cells (ASCs) cultured under conditions of static magnetic field. Investigated cells were exposed to a static magnetic field (MF) with the intensity of 0.5 T. In order to investigate the effects of magnetic field on stem cell signaling, the localization and density and content of microvesicles (MVs) as well as morphology, ultrastructure, and proliferation rate of equine ASCs were evaluated. Results showed that potential of equine adipose-derived mesenchymal stem cells was accelerated when ma...
Mesenchymal stromal cells (MSCs) are multipotent somatic cells that can differentiate into a variety of mature cell types. Over recent years, their biological in vitro and in vivo properties have elicited great expectations in the field of regenerative medicine, immunotherapy and tumour treatment. An increasing number of experimental observations suggest that their biological effects are probably related to a paracrine mechanism via the release of trophic factors and cytokines as well as through the production of membrane vesicles (MVs). These are nanometric membrane-bound structures, comprisi...
Smith RK, Garvican ER, Fortier LA.The horse is an attractive model for many human age-related degenerative diseases of the musculoskeletal system because it is a large animal species that both ages and exercises, and develops naturally occurring injuries with many similarities to the human counterpart. It therefore represents an ideal species to use as a 'proving ground' for new therapies, most notably regenerative medicine. Regenerative techniques using cell-based therapies for the treatment of equine musculoskeletal disease have been in use for over a decade. This review article provides a summary overview of the sources, cu...
Gonçalves NN, Ambrósio CE, Piedrahita JA.Since their original isolation, the majority of the work on embryonic stem cells (ESC) has been carried out in mice. While the mouse is an outstanding model for basic research, it also has considerable limitations for translational work, especially in the area of regenerative medicine. This is due to a combination of factors that include physiological and size differences when compared to humans. In contrast, domestic animal species, such as swine, and companion animal species, such as dogs, provide unique opportunities to develop regenerative medicine protocols that can then be utilized in hu...
Sarrafian TL, Garcia TC, Dienes EE, Murphy B, Stover SM, Galuppo LD.To develop a nonterminal large animal bone defect model for assessing the efficacy of regenerative and pharmacologic treatments designed to enhance bone healing. Methods: In vivo experimental. Methods: Adult gelding horses (n = 6). Methods: Under general anesthesia, using radiographic guidance, 13.5 mm diameter bilateral, full thickness mandibular defects were created in 6 horses using a custom surgical jig and coring bit. After 16 weeks, under general anesthesia, 23 mm diameter cores that encompassed the original healing defects and surrounding parent bone material were removed for evaluation...
Lopez MJ, Jarazo J.According to Greek mythology, Prometheus' liver grew back nightly after it was removed each day by an eagle as punishment for giving mankind fire. Hence, contrary to popular belief, the concept of tissue and organ regeneration is not new. In the early 20th century, cell culture and ex vivo organ preservation studies by Alexis Carrel, some with famed aviator Charles Lindbergh, established a foundation for much of modern regenerative medicine. While early beliefs and discoveries foreshadowed significant accomplishments in regenerative medicine, advances in knowledge within numerous scientific di...
Pascucci L, Alessandri G, Dall'Aglio C, Mercati F, Coliolo P, Bazzucchi C, Dante S, Petrini S, Curina G, Ceccarelli P.Multipotent mesenchymal stromal cells (MSCs) have attracted a great deal of interest, due to several distinctive features, including the ability to migrate to damaged tissue and to participate in tissue regeneration. There is increasing evidence that membrane vesicles (MVs), comprising exosomes and shedding vesicles, represent a key component, responsible for many of the paracrine effects of MSCs. The aim of the present study was to establish whether equine adipose-derived MSCs (E-AdMSCs) produce MVs that are capable of influencing angiogenesis, a key step in tissue regeneration. A morphologic...
Murata D, Miyakoshi D, Hatazoe T, Miura N, Tokunaga S, Fujiki M, Nakayama K, Misumi K.Cartilage regeneration with cell therapy following arthroscopic surgery could be used in racehorses with intra-articular fractures (IAF) and osteochondritis dissecans (OCD). The aims of this study were to investigate the origin and multipotency of stromal cells in the synovial fluid (SF) of horses with intra-articular injury and synovitis, and to provide a new strategy for regeneration of lost articular cartilage. Mesenchymal stromal cells were isolated from SF of horses with IAF and OCD. Multipotency was analysed by RT-PCR for specific mRNAs and staining for production of specific extracellul...
Barsby T, Bavin EP, Guest DJ.The natural reparative mechanisms triggered by tendon damage often lead to the formation of biomechanically inferior scar tissue that is prone to re-injury. Before the efficient application of stem cell-based regenerative therapies, the processes regulating tenocyte differentiation should first be better understood. Three-dimensional (3D) growth environments under strain and the exogenous addition of transforming growth factor beta3 (TGF-β3) have separately been shown to promote tendon differentiation. The aim of this study was to determine the ability of both of these factors to induce tendo...
Textor JA, Murphy KC, Leach JK, Tablin F.To compare fiber diameter, pore area, compressive stiffness, gelation properties, and selected growth factor content of platelet-rich fibrin gels (PRFGs) and conventional fibrin gels (FGs). Methods: PRFGs and conventional FGs prepared from the blood of 10 healthy horses. Methods: Autologous fibrinogen was used to form conventional FGs. The PRFGs were formed from autologous platelet-rich plasma of various platelet concentrations (100 × 10³ platelets/μL, 250 × 10³ platelets/μL, 500 × 10³ platelets/μL, and 1,000 × 10³ platelets/μL). All gels contained an identical fibrinogen concentra...
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...
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...
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...
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...
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...
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....
Hortensius RA, Harley BA.The design of biomaterials for regenerative medicine can require biomolecular cues such as growth factors to induce a desired cell activity. Signal molecules are often incorporated into the biomaterial in either freely-diffusible or covalently-bound forms. However, biomolecular environments in vivo are often complex and dynamic. Notably, glycosaminoglycans (GAGs), linear polysaccharides found in the extracellular matrix, are involved in transient sequestration of growth factors via charge interactions. Biomaterials mimicking this phenomenon may offer the potential to amplify local biomolecular...
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.
Raabe O, Shell K, Fietz D, Freitag C, Ohrndorf A, Christ HJ, Wenisch S, Arnhold S.Mesenchymal stem cells have become extremely interesting for regenerative medicine and tissue engineering in the horse. Stem cell therapy has been proven to be a powerful and successful instrument, in particular for the healing of tendon lesions. We pre-differentiated equine adipose-tissue-derived stem cells (ASCs) in a collagen I gel scaffold by applying tensile strain, growth differentiation factors (GDFs) and various oxygen tensions in order to determine the optimal conditions for in vitro differentiation toward the tenogenic lineage. We compared the influence of 3% versus 21% oxygen tensio...
Sarrafian TL, Garcia TC, Dienes EE, Murphy B, Stover SM, Galuppo LD.To develop a nonterminal large animal bone defect model for assessing the efficacy of regenerative and pharmacologic treatments designed to enhance bone healing. Methods: In vivo experimental. Methods: Adult gelding horses (n = 6). Methods: Under general anesthesia, using radiographic guidance, 13.5 mm diameter bilateral, full thickness mandibular defects were created in 6 horses using a custom surgical jig and coring bit. After 16 weeks, under general anesthesia, 23 mm diameter cores that encompassed the original healing defects and surrounding parent bone material were removed for evaluation...
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...
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...
Song K, Yang GM, Han J, Gil M, Dayem AA, Kim K, Lim KM, Kang GH, Kim S, Jang SB, Vellingiri B, Cho SG.Flavonoids form the largest group of plant phenols and have various biological and pharmacological activities. In this study, we investigated the effect of a flavonoid, 3, 4'-dihydroxyflavone (3, 4'-DHF) on osteogenic differentiation of equine adipose-derived stromal cells (eADSCs). Unassigned: Treatment of 3, 4'-DHF led to increased osteogenic differentiation of eADSCs by increasing phosphorylation of ERK and modulating Reactive Oxygen Species (ROS) generation. Although PD98059, an ERK inhibitor, suppressed osteogenic differentiation, another ERK inhibitor, U0126, apparently increased osteoge...
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...
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 ...
Jacquet-Guibon S, Dupays AG, Coudry V, Crevier-Denoix N, Leroy S, Siñeriz F, Chiappini F, Barritault D, Denoix JM.A randomized controlled trial was performed on racing horses, to evaluate the efficacy of a new class of therapeutic agents in regenerative medicine-ReGeneraTing Agents® (RGTA®), to treat tendinopathies. Preliminary uncontrolled studies on tendon healing in racing horses with RGTA® (OTR4131)-Equitend® showed encouraging results, justifying performing a randomized, controlled, multicenter study with a two-year racing performance follow up. The objective of this study was to evaluate the effect of Equitend® versus placebo on acute superficial digital flexor tendonitis in racing French Stand...
Michler JK, Hillmann A, Savkovic V, Mülling CKW.The easily accessible niche represented by skin and its appendages may serve as a promising source to complement modern regenerative medicine for horses. In humans and in animal models for human medicine, the hair follicle and its stem cell niches are well characterized. Since literature in this field of equine research is scarce, we sought to analyze cells of the dermal stem cell niche of the equine hair follicle morphologically and for a subset of markers useful for cell characterization via immunolabeling. We cultured equine forelock skin explants to obtain cultures with cells migrating fro...
Duysens J, Graide H, Niesten A, Mouithys-Mickalad A, Deby-Dupont G, Franck T, Ceusters J, Serteyn D.Muscle-derived mesenchymal stromal cells (mdMSCs) hold great promise in regenerative medicine due to their immunomodulatory properties, multipotent differentiation capacity and ease of collection. However, traditional in vitro expansion methods use fetal bovine serum (FBS) and have numerous limitations including ethical concerns, batch-to-batch variability, immunogenicity, xenogenic contamination and regulatory compliance issues. This study investigates the use of 10% equine platelet lysate (ePL) obtained by plasmapheresis as a substitute for FBS in the culture of mdMSCs in innovative 2D and 3...
Gilger BC.Regenerative therapy and biologics have the promise to treat equine ocular surface diseases, including corneal ulceration or immune-mediated keratitis, or intraocular diseases such as uveitis. The use of blood-derived products such as serum or platelet-rich plasma, mesenchymal stem cells, or amniotic membrane grafts may be beneficial for the treatment of ulcerative and chronic keratitis in horses. Furthermore, the use of stem cells or gene therapy has promise for the treatment of Intraocular diseases such as equine recurrent uveitis by providing efficacious, practical, and long-term therapy fo...
Furuoka H, Shirakawa T, Taniyama H, Ohishi H, Satoh H, Itakura C.Pancreatic tissue from 20 horses was examined using immunocytochemical techniques. In aged horses, neogenesis of endocrine cells, neoformation, and hyperplasia of islets occurred closely associated with the pancreatic duct; these changes were regarded as nesidioblastosis. In addition, pancreatic fibrosis accompanied by ductal proliferation and endocrine neogenesis was considered a regenerative change. Thus, the origin of neoformation in the endocrine pancreas was in the ductal system, and it is suggested that the pancreatic endocrine cells were of endodermal origin.
Boone L, Peroni J.Regenerative medicine is defined as the process of replacing or regenerating cells, tissues, or organs to restore or establish normal function. The use of regenerative medicine in equine practice to treat injured musculoskeletal tissues with limited capacity for intrinsic healing is growing. This article provides the practitioner with a brief and basic overview of the regenerative products currently used in equine practice.
Pluim M, Heier A, Plomp S, Boshuizen B, Gröne A, van Weeren R, Vanderperren K, Martens A, Dewulf J, Chantziaras I, Koene M, Luciani A, Oosterlinck M....High-power laser therapy gained popularity recently as a regenerative treatment for tendinitis and desmitis in the horse. However, studies evaluating the effects of laser therapy on tissue repair at the histological level in large mammals are lacking. Objective: To evaluate the effects of high-power laser therapy on suspensory desmitis healing, using a model of suspensory ligament branch injury. Methods: In vivo experiments. Methods: Standardised lesions were surgically induced in all four lateral suspensory branches of 12 healthy Warmblood horses. Laser therapy (class 4, 15W) was applied dail...
Eydt C, Geburek F, Schröck C, Hambruch N, Rohn K, Pfarrer C, Staszyk C.Aspiration of equine sternal bone marrow is required for the cultivation of bone marrow-derived multipotent mesenchymal stromal cells (BM-MSCs) for regenerative therapies. For bone marrow aspiration as well as for MSC cultivation, there is a need to optimize techniques and protocols to enhance MSC harvest at minimized culture times. In a comparative study bone marrow aspirates from sternebra 4 and 5 were collected at two different positions within the sternebrae, either from 10 mm or from 30 mm dorsal from the ventral margin of the sternebrae. Accuracy of the puncture depth was confirmed by ...
Clarke EJ, Gillen A, Turlo A, Peffers MJ.Horses are used in a variety of equestrian disciplines predisposing them to musculoskeletal injury or disease including osteoarthritis and tendinopathy. As a result, a number of preventative measures are used within equine medicine and husbandry, ranging from therapeutic shoeing to the use of nutraceuticals. Despite their popularity and routine use evidence base and clinical outcomes are variable, bringing into question the efficacy of these prophylactic measures. In recent years a small number of studies have been performed examining the effect of specific strategies in order to quantify the ...
Miranda CMFC, Therrien J, Leonel LCPC, Smith OE, Miglino MA, Smith LC.Equine represents an attractive animal model for musculoskeletal tissue diseases, exhibiting much similarity to the injuries that occur in humans. Cell therapy and tissue bioengineering have been widely used as a therapeutic alternative by regenerative medicine in musculoskeletal diseases. Thus, the aim of this study was to produce an acellular biomaterial of equine skeletal muscle and to evaluate its effectiveness in supporting the in vitro culture of equine induced pluripotency stem cells (iPSCs). Biceps femoris samples were frozen at -20°C for 4 days and incubated in 1% sodium dodecyl s...
Petrova V, Vachkova E.Adipose tissue is recognized as the major endocrine organ, potentially acting as a source of mesenchymal stem cells for various applications in regenerative medicine. Athletic horses are often exposed to traumatic injuries, resulting in severe financial losses. The development of adipose-derived stem cells' regenerative potential depends on many factors. The extraction of stem cells from subcutaneous adipose tissue is non-invasive, non-traumatic, cheaper, and safer than other sources. Since there is a lack of unique standards for identification, the isolated cells and applied differentiation p...
Watts AE.Mesenchymal stem cells (MSCs) are used as a regenerative therapy in horses for musculoskeletal injury since the late 1990s and in some regions are standard of care for certain injuries. Yet, there is no Food and Drug Administration-approved MSC therapeutic in the United States for horses. In humans, lack of regulatory approval in the United States has been caused by failure of late-phase clinical trials to demonstrate consistent efficacy, perhaps because of nonuniformity of MSC preparation and application techniques. This article discusses clinical evidence for musculoskeletal applications of ...
Abd El-Rahman SS, Amer MS, Hassan MH, Fahmy HM, Shamaa AA.Lyophilized equine platelet derived growth factors (LGF) is a novel advanced platelet rich protein growth factor. It has been successfully applied in various fields of regenerative medicine to treat a variety of inflammatory and degenerative musculoskeletal conditions. Our study aimed to evaluate the efficacy of intraarticularly injected LGF for the remedy of articular cartilage injury, commonly characterized by progressive pain and loss of joint function in osteoarthritic rabbits. Full-thickness cylindrical cartilage defects were generated in both femoral condylar articular surfaces in twenty...
Falk J, Donadeu FX.Groundbreaking work by Takahashi and Yamanaka in 2006 demonstrated that non-embryonic cells can be reprogrammed into pluripotent stem cells (PSCs) by forcing the expression of a defined set of transcription factors in culture, thus overcoming ethical concerns linked to embryonic stem cells. Induced PSCs have since revolutionized biomedical research, holding tremendous potential also in other areas such as livestock production and wildlife conservation. iPSCs exhibit broad accessibility, having been derived from a multitude of cell types and species. Apart from humans, iPSCs hold particular med...
Leal Reis I, Lopes B, Sousa P, Sousa AC, Branquinho MV, Caseiro AR, Rêma A, Briote I, Mendonça CM, Santos JM, Atayde LM, Alvites RD, Maurício AC.Horses are high-performance athletes prone to sportive injuries such as tendonitis and desmitis. The formation of fibrous tissue in tendon repair remains a challenge to overcome. This impels regenerative medicine to develop innovative therapies that enhance regeneration, retrieving original tissue properties. Multipotent Mesenchymal Stem/Stromal Cells (MSCs) have been successfully used to develop therapeutic products, as they secrete a variety of bioactive molecules that play a pivotal role in tissue regeneration. These factors are released in culture media for producing a conditioned medium (...
Klymiuk MC, Balz N, Elashry MI, Wenisch S, Arnhold S.Nanoparticles including extracellular vesicles derived from mesenchymal stem cells are of increasing interest for research and clinical use in regenerative medicine. Extracellular vesicles (EVs), including also previously named exosomes, provide a promising cell-free tool for therapeutic applications, which is probably a safer approach to achieve sufficient healing. Storage of EVs may be necessary for clinical applications as well as for further experiments, as the preparation is sometimes laborious and larger quantities tend to be gained. For this purpose, nanoparticles were obtained from mes...
Reis IL, Lopes B, Sousa P, Sousa AC, Rêma A, Caseiro AR, Briote I, Rocha AM, Pereira JP, Mendonça CM, Santos JM, Lamas L, Atayde LM, Alvites RD....Here, we describe a case of a 5-year-old show-jumping stallion presented with severe lameness, swelling, and pain on palpation of the left metacarpophalangeal joint (MCj). Diagnostic imaging revealed full and partial-thickness articular defects over the lateral condyle of the third metacarpus (MC3) and the dorsolateral aspect of the first phalanx (P1). After the lesion's arthroscopic curettage, the patient was subjected to an innovative regenerative treatment consisting of two intra-articular injections of equine synovial membrane mesenchymal stem/stromal cells (eSM-MSCs) combined with umbilic...
Casado-Santos A, González-Cubero E, González-Fernández ML, González-Rodríguez Y, García-Rodríguez MB, Villar-Suárez V.Corneal ulcers are a common and potentially vision-threatening condition in horses that can be challenging to treat with conventional therapies alone. This case report describes the successful treatment of a non-healing corneal ulcer in a 28-year-old Hispano-Bretón mare using the secretome derived from adipose tissue-derived mesenchymal stem cells (ASCs). Despite initial treatment with antibiotics, anti-inflammatory drugs, and surgical debridement, the corneal ulcer failed to heal properly, exhibiting persistent epithelial defects and stromal complications. As an alternative regenerative appr...
Carmona JU, Carmona-Ramírez LH, López C.(1) Background: There is increasing interest in the use of platelet-rich plasma and related orthobiologics for the treatment of chronic musculoskeletal disorders in horses; however, there is no information on the bibliometric impact of the literature published in this area. (2) Methods: A bibliometric analysis was performed using the bibliometrix R package by analyzing the documents registered in the WOS and Scopus databases from 2000 to 2024. The included registers were evaluated according to the menu of results from the biblioshiny web app (overview, sources, authors, documents, words, trend...
Elashry MI, Speer J, De Marco I, Klymiuk MC, Wenisch S, Arnhold S.Osteoarthritis (OA) is a chronic progressive degenerative joint disease that affects a significant portion of the equine population and humans worldwide. Current treatment options for equine OA are limited and incompletely curative. Horses provide an excellent large-animal model for studying human OA. Recent advances in the field of regenerative medicine have led to the exploration of extracellular vesicles (EVs)-cargoes of microRNA, proteins, lipids, and nucleic acids-to evaluate their diagnostic value in terms of disease progression and severity, as well as a potential cell-free therapeutic ...
Gaspari G, Lange-Consiglio A, Cremonesi F, Desantis S.Extracellular vesicles (EVs) are important mediators of cell-cell communication thanks to their ability to transfer their bioactive cargo, thus regulating a variety of physiological contexts. EVs derived from amniotic mesenchymal/stromal cells (eAMC-EVs) are internalized by equine endometrial cells (eECs) with positive effects on regenerative medicine treatments. As the cellular uptake of EVs is influenced by the glycan profile of both EVs and target cells, this study is focused on the role of surface glycans in the uptake of eAMC-EVs by recipient eECs. Equine ECs were obtained by enzymatic di...
Li D, Wang X, Yao J, Chen S.Adipose tissue-derived extracellular vesicles (ATEVs) have garnered attention for their roles in intercellular communication and regulation. This study presents the first investigation of equine adipose tissue, with ATEV being extracted concurrently during the isolation of adipose-derived mesenchymal stem cells (ADSCs). Through CCK-8 cell proliferation assays and scratch migration assays, a significant promotional effect of ATEV on ADSCs was observed, which not only accelerated the proliferation rate of the stem cells but also enhanced their migratory capacity. The application of Trypan Blue e...
Harman RM, Rajesh A, Van de Walle GR.Treatment of skin wounds is a high priority in veterinary medicine because healthy uncompromised skin is essential for the well-being of horses. Stem cells and other biologic therapies offer benefits by reducing the need for surgical procedures and conventional antibiotics. Evidence from in vitro studies and small in vivo trials supports the use of equine stem cells and biologics for the treatment of acute and chronic cutaneous wounds. Larger clinical trials are warranted to better evaluate the regenerative and immunological responses to these treatments. Additionally, delivery methods and t...
