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.
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...
Mocchi M, Grolli S, Dotti S, Di Silvestre D, Villa R, Berni P, Conti V, Passignani G, Brambilla F, Bue MD, Catenacci L, Sorrenti M, Segale L, Bari E....In the last decades, it has been demonstrated that the regenerative therapeutic efficacy of mesenchymal stromal cells is primarily due to the secretion of soluble factors and extracellular vesicles, collectively known as secretome. In this context, our work described the preparation and characterization of a freeze-dried secretome (Lyosecretome) from adipose tissue-derived mesenchymal stromal cells for the therapy of equine musculoskeletal disorder. An intraarticular injectable pharmaceutical powder has been formulated, and the technological process has been validated in an authorized facility...
Garnica-Galvez S, Korntner SH, Skoufos I, Tzora A, Diakakis N, Prassinos N, Zeugolis DI.The use of macromolecular crowding in the development of extracellular matrix-rich cell-assembled tissue equivalents is continuously gaining pace in regenerative engineering. Despite the significant advancements in the field, the optimal macromolecular crowder still remains elusive. Herein, the physicochemical properties of different concentrations of different molecular weights hyaluronic acid (HA) and their influence on equine adipose-derived stem cell cultures were assessed. Within the different concentrations and molecular weight HAs, the 10 mg/mL 100 kDa and 500 kDa HAs exhibited the high...
Elashry MI, Baulig N, Wagner AS, Klymiuk MC, Kruppke B, Hanke T, Wenisch S, Arnhold S.Combination of mesenchymal stem cells (MSCs) and biomaterials is a rapidly growing approach in regenerative medicine particularly for chronic degenerative disorders including osteoarthritis and osteoporosis. The present study examined the effect of biomaterial scaffolds on equine adipose-derived MSC morphology, viability, adherence, migration, and osteogenic differentiation. MSCs were cultivated in conjunction with collagen CultiSpher-S Microcarrier (MC), nanocomposite xerogels B30 and combined B30 with strontium (B30Str) biomaterials in osteogenic differentiation medium either under static or...
Ribitsch I, Oreff GL, Jenner F.Musculoskeletal injuries and chronic degenerative diseases commonly affect both athletic and sedentary horses and can entail the end of their athletic careers. The ensuing repair processes frequently do not yield fully functional regeneration of the injured tissues but biomechanically inferior scar or replacement tissue, causing high reinjury rates, degenerative disease progression and chronic morbidity. Regenerative medicine is an emerging, rapidly evolving branch of translational medicine that aims to replace or regenerate cells, tissues, or organs to restore or establish normal function. It...
Bukowska J, Szóstek-Mioduchowska AZ, Kopcewicz M, Walendzik K, Machcińska S, Gawrońska-Kozak B.Adipose-derived stem cells (ASCs) isolated from domestic animals fulfill the qualitative criteria of mesenchymal stem cells, including the capacity to differentiate along multiple lineage pathways and to self-renew, as well as immunomodulatory capacities. Recent findings on human diseases derived from studying large animal models, have provided evidence that administration of autologous or allogenic ASCs can improve the process of healing. In a narrow group of large animals used in bioresearch studies, pigs and horses have been shown to be the best suited models for study of the wound healing ...
Navarrete F, Wong YS, Cabezas J, Riadi G, Manríquez J, Rojas D, Furlanetto Mançanares AC, Rodriguez-Alvarez L, Saravia F, Castro FO.Equine endometrial and adipose mesenchymal stem cells (eMSCs and aMSCs, respectively) were isolated from the same donors of thoroughbred mares. The cells displayed characteristic features of MSCs, including trilineage mesodermal and also neurogenic differentiation. We evaluated the influence of cellular origin on their transcriptome profile. Cellular RNA was isolated and sequenced and extracellular vesicles (EVs) were obtained from conditioned medium of cells cultured in medium depleted of EVs, and their microRNA (miRNA) cargo analyzed by sequencing. Differential expression of mRNAs and EV-miR...
Javanshir S, Younesi Soltani F, Dowlati G, Parham A, Naderi-Meshkin H.Managing tendon healing process is complicated mainly due to the limited regeneration capacity of tendon tissue. Mesenchymal stem cells (MSCs) have potential applications in regenerative medicine and have been considered for tendon repair and regeneration. This study aimed to evaluate the capacity of equine adipose tissue-derived cells (eASCs) to differentiate into tenocytes in response to platelet-derived growth factor-BB (PDGF-BB) and growth differentiation factor-6 (GDF-6) in vitro. Frozen characterized eASCS of 3 mares were thawed and the cells were expanded in basic culture medium (DMEM...
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...
Aimaletdinov A, Mindubaeva G, Khalikova S, Kabwe E, Salmakova A, Alexandrova N, Rutland C, Rizvanov A, Zakirova E.Tendon injuries are one of the most common causes of orthopedic disorders in horses. Such injuries involve a long course of treatment and recovery. The most promising method of treating these injuries is the use of recombinant proteins and gene therapy. In this work, we evaluated the therapeutic efficacy of plasmid DNA (pDNA) containing two species-specific coding sequences, i.e. vascular endothelial growth factor 164 (VEGF164) and fibroblast growth factor 2 (FGF2), in the treatment of severe damage to the tendon of the superficial digital flexor. A pDNA construct was used to restore the damag...
Mocchi M, Dotti S, Bue MD, Villa R, Bari E, Perteghella S, Torre ML, Grolli S.Regenerative medicine aims to restore the normal function of diseased or damaged cells, tissues, and organs using a set of different approaches, including cell-based therapies. In the veterinary field, regenerative medicine is strongly related to the use of mesenchymal stromal cells (MSCs), which belong to the body repair system and are defined as multipotent progenitor cells, able to self-replicate and to differentiate into different cell types. This review aims to take stock of what is known about the MSCs and their use in the veterinary medicine focusing on clinical reports on dogs and hors...
Voga M, Adamic N, Vengust M, Majdic G.Regenerative medicine is a branch of medicine that develops methods to grow, repair, or replace damaged or diseased cells, organs or tissues. It has gained significant momentum in recent years. Stem cells are undifferentiated cells with the capability to self-renew and differentiate into tissue cells with specialized functions. Stem cell therapies are therefore used to overcome the body's inability to regenerate damaged tissues and metabolic processes after acute or chronic insult. The concept of stem cell therapy was first introduced in 1991 by Caplan, who proposed that massive differentiatio...
Paterson YZ, Cribbs A, Espenel M, Smith EJ, Henson FMD, Guest DJ.Tendon injuries occur frequently in human and equine athletes. Treatment options are limited, and the prognosis is often poor with functionally deficient scar tissue resulting. Fetal tendon injuries in contrast are capable of healing without forming scar tissue. Embryonic stem cells (ESCs) may provide a potential cellular therapeutic to improve adult tendon regeneration; however, whether they can mimic the properties of fetal tenocytes is unknown. To this end, understanding the unique expression profile of normal adult and fetal tenocytes is crucial to allow validation of ESC-derived tenocytes...
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...
da Silva LL, Silveira MD, da Costa Garcia CAS, Grudzinski PB, Martins CF, Nardi NB.Mesenchymal stromal cells (MSCs) have attracted great attention for therapeutic applications. Since cells derived from different tissues have different properties, using the right tissue source may impact their efficiency in regenerative medicine. This study describes for the first time the isolation and characterization of MSCs derived from the equine coronary corium, which may be useful for treating diseases such as laminitis. Seven coronary corium samples were used for isolation of cells (ccMSCs). Adherent cells were characterized for morphology, immunophenotype, proliferation and different...
Al Naem M, Bourebaba L, Kucharczyk K, Röcken M, Marycz K.Mesenchymal stromal cells (MSC) have become a popular treatment modality in equine orthopaedics. Regenerative therapies are especially interesting for pathologies like complicated tendinopathies of the distal limb, osteoarthritis, osteochondritis dissecans (OCD) and more recently metabolic disorders. Main sources for MSC harvesting in the horse are bone marrow, adipose tissue and umbilical cord blood. While the acquisition of umbilical cord blood is fairly easy and non-invasive, extraction of bone marrow and adipose tissue requires more invasive techniques. Characterization of the stem cells a...
Cong X, Zhang SM, Ellis MW, Luo J.Induced pluripotent stem cell (iPSC) technology offers a practically infinite and ethically acceptable source to obtain a variety of somatic cells. Coupled with the biotechnologies of cell therapy or tissue engineering, iPSC technology will enormously contribute to human regenerative medicine. Before clinical application, such human iPSC (hiPSC)-based therapies should be assessed using large animal models that more closely match biological or biomechanical properties of human patients. Therefore, it is critical to generate large animal iPSCs, obtain their iPSC-derived somatic cells, and precli...
Shojaee A, Parham A, Ejeian F, Nasr Esfahani MH.Equine adipose-derived mesenchymal stem cells (eq-ASCs) possess excellent regeneration potential especially for treatment of musculoskeletal disorders. Besides their common characteristics, MSCs harvested from different species reveal some species-specific and donor-dependent behaviors. Hence, the molecular analysis of MSCs may shed more light on their future clinical application of these cells. This study aimed to investigate some behavioral aspects of eq-ASCs in vitro which may influence the efficacy of stem cell therapy. For this purpose, MSCs of a donor horse were isolated, characterized a...
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.
Baird A, Dominguez Falcon N, Saeed A, Guest DJ.Horses, like humans, can experience bone fractures and due to their large size and the need to bear weight on all limbs during the recovery period, they can be difficult to treat. Surgical techniques to improve fracture repair are improving, but to date, regenerative medicine technologies to aid fracture healing are not commonly applied in horses. We have previously demonstrated that equine induced pluripotent stem cells (iPSCs) can be differentiated into bone forming osteoblasts in 2D culture. In this study, we report on the use of a thermoplastic, 3D-printed polymer to provide a scaffold for...
Bourebaba L, Röcken M, Marycz K.Osteochondrosis (osteochondrosis dissecans; OCD) is a disease syndrome of growing cartilage related to different clinical entities such as epiphysitis, subchondral cysts and angular carpal deformities, which occurs in growing animals of all species, including horses. Nowadays, these disorders are affecting increasing numbers of young horses worldwide. As a complex multifactorial disease, OCD is initiated when failure in cartilage canals because of existing ischemia, chondrocyte biogenesis impairment as well as biochemical and genetic disruptions occur. Recently, particular attention have been ...
Lanci A, Merlo B, Mariella J, Castagnetti C, Iacono E.A complex feedback of growth factors, secreted by a variety of cell types, is responsible for the mediation of skin healing. Despite the recent advances in wound healing management, this fails up to 50% and skin wounds can still be considered one of the main causes of morbidity, both in human and veterinary medicine. Regenerative medicine, involving mesenchymal stromal cells (MSCs), is nowadays a promising solution for skin wound healing. Indeed, MSCs are involved in the modulation of the inflammatory local response and cell replacing, by a paracrine mode of action. Local application of equine...
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.
Boere J, Malda J, van de Lest CHA, van Weeren PR, Wauben MHM.The use of extracellular vesicles (EVs) as a potential therapy is currently explored for different disease areas. When it comes to the treatment of joint diseases this approach is still in its infancy. As in joint diseases both inflammation and the associated articular tissue destruction are important factors, both the immune-suppressive and the regenerative properties of EVs are potentially advantageous characteristics for future therapy. There is, however, only limited knowledge on the basic features, such as numerical profile and function, of EVs in joint articular tissues in general and th...
Viganò M, Tessaro I, Trovato L, Colombini A, Scala M, Magi A, Toto A, Peretti G, de Girolamo L.The management of cartilage lesions is an open issue in clinical practice, and regenerative medicine represents a promising approach, including the use of autologous micrografts whose efficacy was already tested in different clinical settings. The aim of this study was to characterize in vitro the effect of autologous cartilage micrografts on chondrocyte viability and differentiation and perform an evaluation of their application in racehorses affected by joint diseases. Methods: Matched human chondrocytes and micrografts were obtained from articular cartilage using Rigenera® procedure. Chond...
Rakic R, Bourdon B, Demoor M, Maddens S, Saulnier N, Galéra P.Umbilical cord blood mesenchymal stromal/stem cells (UCB-MSCs) and umbilical cord matrix MSCs (UCM-MSCs) have chondrogenic potential and are alternative sources to standard surgically derived bone marrow or adipose tissue collection for cartilage engineering. However, the majority of comparative studies explore neonatal MSCs potential only on ISCT benchmark assays accounting for some bias in the reproducibility between in vitro and in clinical studies. Therefore, we characterized equine UCB-MSCs and UCM-MSCs and investigated with particular attention their chondrogenesis potential in 3D cultu...
Cortés-Araya Y, Amilon K, Rink BE, Black G, Lisowski Z, Donadeu FX, Esteves CL.Equine mesenchymal stem/stromal cells (MSCs) are multipotent cells that are widely used for treatment of musculoskeletal injuries, and there is significant interest in expanding their application to nonorthopedic conditions. MSCs possess antibacterial and immunomodulatory properties that may be relevant for combating infection; however, comparative studies using MSCs from different origins have not been carried out in the horse, and this was the focus of this study. Our results showed that MSC-conditioned media attenuated the growth of Escherichia coli, and that this effect was, on average, mo...
Lee EB, Kim JW, Seo JP.Platelet rich plasma (PRP) is popularly used in the horse industry to enhance regeneration of tissue injury that has limitation of blood supply. This study aimed to compare the methods for platelet rich plasma preparation since they has not been established yet. Blood was collected from six horses and platelets were concentrated by three different methods (2-step centrifugation, separated centrifugation and separated centrifugation using histopaque). Concentrated blood was analyzed using Advia hematology systems. In the result, separated centrifugation with histopaque showed the significantly ...
Conrad S, Weber K, Walliser U, Geburek F, Skutella T.In adults the healing tendon generates fibrovascular scar tissue and recovers never histologically, mechanically, and functionally which leads to chronic and to degenerative diseases. In this review, the processes and mechanisms of tendon development and fetal regeneration in comparison to adult defect repair and degeneration are discussed in relation to regenerative therapeutic options. We focused on the application of stem cells, growth factors, transcription factors, and gene therapy in tendon injury therapies in order to intervene the scarring process and to induce functional regeneration ...
Baird A, Lindsay T, Everett A, Iyemere V, Paterson YZ, McClellan A, Henson FMD, Guest DJ.Bone fractures occur in horses following traumatic and non-traumatic (bone overloading) events. They can be difficult to treat due to the need for the horse to bear weight on all legs during the healing period. Regenerative medicine to improve fracture union and recovery could significantly improve horse welfare. Equine induced pluripotent stem cells (iPSCs) have previously been derived. Here we show that equine iPSCs cultured for 21 days in osteogenic induction media on an OsteoAssay surface upregulate the expression of osteoblast associated genes and proteins, including , , , , and We al...
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...
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...
Baird A, Lindsay T, Everett A, Iyemere V, Paterson YZ, McClellan A, Henson FMD, Guest DJ.Bone fractures occur in horses following traumatic and non-traumatic (bone overloading) events. They can be difficult to treat due to the need for the horse to bear weight on all legs during the healing period. Regenerative medicine to improve fracture union and recovery could significantly improve horse welfare. Equine induced pluripotent stem cells (iPSCs) have previously been derived. Here we show that equine iPSCs cultured for 21 days in osteogenic induction media on an OsteoAssay surface upregulate the expression of osteoblast associated genes and proteins, including , , , , and We al...
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...
Mocchi M, Grolli S, Dotti S, Di Silvestre D, Villa R, Berni P, Conti V, Passignani G, Brambilla F, Bue MD, Catenacci L, Sorrenti M, Segale L, Bari E....In the last decades, it has been demonstrated that the regenerative therapeutic efficacy of mesenchymal stromal cells is primarily due to the secretion of soluble factors and extracellular vesicles, collectively known as secretome. In this context, our work described the preparation and characterization of a freeze-dried secretome (Lyosecretome) from adipose tissue-derived mesenchymal stromal cells for the therapy of equine musculoskeletal disorder. An intraarticular injectable pharmaceutical powder has been formulated, and the technological process has been validated in an authorized facility...
Khaled MM, Ibrahium AM, Abdelgalil AI, El-Saied MA, El-Bably SH.Peripheral nerve damage mainly resulted from traumatic or infectious causes; the main signs of a damaged nerve are the loss of sensory and/or motor functions. The injured nerve has limited regenerative capacity and is recovered by the body itself, the recovery process depends on the severity of damage to the nerve, nowadays the use of stem cells is one of the new and advanced methods for treatment of these problems. Following our review, data are collected from different databases "Google scholar, Springer, Elsevier, Egyptian Knowledge Bank, and PubMed" using different keywords such as Periphe...
Pérez Fraile A, González-Cubero E, Martínez-Flórez S, Olivera ER, Villar-Suárez V.Musculoskeletal injuries in horses have a great economic impact, predominantly affecting tendons, ligaments, and cartilage, which have limited natural regeneration. Cell therapy, which uses mesenchymal stem cells due to their tissue differentiation properties and anti-inflammatory and immunoregulatory effects, aims to restore damaged tissue. In this manuscript, we performed a systematic review using the Parsifal tool, searching the PubMed and Web of Science databases for articles on regenerative medicine for equine musculoskeletal injuries. Our review covers 17 experimental clinical studies ca...
Reis IL, Lopes B, Sousa P, Sousa AC, Caseiro AR, Mendonça CM, Santos JM, Atayde LM, Alvites RD, Maurício AC.Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managin...
Bourebaba L, Röcken M, Marycz K.Osteochondrosis (osteochondrosis dissecans; OCD) is a disease syndrome of growing cartilage related to different clinical entities such as epiphysitis, subchondral cysts and angular carpal deformities, which occurs in growing animals of all species, including horses. Nowadays, these disorders are affecting increasing numbers of young horses worldwide. As a complex multifactorial disease, OCD is initiated when failure in cartilage canals because of existing ischemia, chondrocyte biogenesis impairment as well as biochemical and genetic disruptions occur. Recently, particular attention have been ...
Melzer M, Schubert S, Müller SF, Geyer J, Hagen A, Niebert S, Burk J.Mesenchymal stromal cells (MSC) represent a promising therapeutic tool for tendon regeneration. Their tenogenic differentiation is crucial for tissue engineering approaches and may support their beneficial effects after cell transplantation . The transforming growth factor (TGF)-, signalling via intracellular Smad molecules, is a potent paracrine mediator of tenogenic induction. Moreover, scaffold topography or tendon matrix components induced tenogenesis via activation of the Rho/ROCK cascade, which, however, is also involved in pathological adaptations in extracellular matrix pathologies. Th...
González Vázquez AG, Blokpoel Ferreras LA, Bennett KE, Casey SM, Brama PA, O'Brien FJ.Joint repair remains a major challenge in orthopaedics. Recent progress in biomaterial design has led to the fabrication of a plethora of promising devices. Pre-clinical testing of any joint repair strategy typically requires the use of large animal models (e.g., sheep, goat, pig or horse). Despite the key role of such models in clinical translation, there is still a lack of consensus regarding optimal experimental design, making it difficult to draw conclusions on their efficacy. In this context, the authors performed a systematic literature review and a risk of bias assessment on large anima...
Cokelaere S, Malda J, van Weeren R.Chondral and osteochondral lesions due to injury or other pathology are highly prevalent conditions in horses (and humans) and commonly result in the development of osteoarthritis and progression of joint deterioration. Regenerative medicine of articular cartilage is an emerging clinical treatment option for patients with articular cartilage injury or disease. Functional articular cartilage restoration, however, remains a major challenge, but the field is progressing rapidly and there is an increasing body of supportive clinical and scientific evidence. This review gives an overview of the est...
Zayed M, Adair S, Ursini T, Schumacher J, Misk N, Dhar M.Osteoarthritis (OA), the most common form of joint disease affecting humans and horses, is characterized by the advance and decline of cartilage and loss of function of the affected joint. The progression of OA is steadily accompanied with biochemical events, which interfere with the cytokines and proteolytic enzymes responsible for progress of the disease. Recently, regenerative therapies have been used with an assumption that mesenchymal stem cells (MSCs) possess the potential to prevent the advancement of cartilage damage and potentially regenerate the injured tissue with an ultimate goal o...
Elashry MI, Baulig N, Wagner AS, Klymiuk MC, Kruppke B, Hanke T, Wenisch S, Arnhold S.Combination of mesenchymal stem cells (MSCs) and biomaterials is a rapidly growing approach in regenerative medicine particularly for chronic degenerative disorders including osteoarthritis and osteoporosis. The present study examined the effect of biomaterial scaffolds on equine adipose-derived MSC morphology, viability, adherence, migration, and osteogenic differentiation. MSCs were cultivated in conjunction with collagen CultiSpher-S Microcarrier (MC), nanocomposite xerogels B30 and combined B30 with strontium (B30Str) biomaterials in osteogenic differentiation medium either under static or...
Cong X, Zhang SM, Ellis MW, Luo J.Induced pluripotent stem cell (iPSC) technology offers a practically infinite and ethically acceptable source to obtain a variety of somatic cells. Coupled with the biotechnologies of cell therapy or tissue engineering, iPSC technology will enormously contribute to human regenerative medicine. Before clinical application, such human iPSC (hiPSC)-based therapies should be assessed using large animal models that more closely match biological or biomechanical properties of human patients. Therefore, it is critical to generate large animal iPSCs, obtain their iPSC-derived somatic cells, and precli...
Koch DW, Schnabel LV, Ellis IM, Bates RE, Berglund AK.Mesenchymal stem cells (MSCs) secrete paracrine factors and extracellular matrix proteins that contribute to their ability to support tissue healing and regeneration. Both the transcriptome and the secretome of MSCs can be altered by treating the cells with cytokines, but neither have been thoroughly investigated following treatment with the specific cytokine transforming growth factor (TGF)-β2. RNA-sequencing and western blotting were used to compare gene and protein expression between untreated and TGF-β2-treated equine bone marrow-derived MSCs (BM-MSCs). A co-culture system was utilized t...
Conrad S, Weber K, Walliser U, Geburek F, Skutella T.In adults the healing tendon generates fibrovascular scar tissue and recovers never histologically, mechanically, and functionally which leads to chronic and to degenerative diseases. In this review, the processes and mechanisms of tendon development and fetal regeneration in comparison to adult defect repair and degeneration are discussed in relation to regenerative therapeutic options. We focused on the application of stem cells, growth factors, transcription factors, and gene therapy in tendon injury therapies in order to intervene the scarring process and to induce functional regeneration ...
Tidd N, Michelsen J, Hilbert B, Quinn JC.Gene-directed tissue repair offers the clinician, human or veterinary, the chance to enhance cartilage regeneration and repair at a molecular level. Non-viral plasmid vectors have key biosafety advantages over viral vector systems for regenerative therapies due to their episomal integration however, conventional non-viral vectors can suffer from low transfection efficiency. Our objective was to identify and validate in vitro a novel non-viral gene expression vector that could be utilized for ex vivo and in vivo delivery to stromal-derived mesenchymal stem cells (MSCs). Minicircle plasmid DNA v...
Taylor SE, Clegg PD.Mesenchymal stromal cells (MSC) are derived from adult mesenchymal tissues and have the ability to undergo differentiation into bone, cartilage, and fat, and have therefore attracted great interest in regenerative medicine. Many isolation and culture methods have been described, making comparison between laboratories and quality-control protocols difficult. A uniform protocol to characterize equine MSC has recently been proposed, aiming to introduce consistency across the equine stem cell research field. This article reviews the published techniques for collection and propagation of equine MSC...
De Schauwer C, van de Walle GR, Piepers S, Hoogewijs MK, Govaere JL, Meyer E, van Soom A.The therapeutic potential of mesenchymal stromal cells for cellular therapy has generated increasing interest in human as well as veterinary medicine. Considerable research has been performed on the cryopreservation of expanded mesenchymal stromal cells, but little information is available on the cryopreservation of the original mononuclear cell fraction. Objective: The present study describes a protocol to expand equine mesenchymal stromal cells after cryopreserving the mononuclear cells of umbilical cord blood. Methods: To this end, mononuclear cells were isolated from 7 umbilical cord blood...
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...
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...
Seo MS, Park SB, Kim HS, Kang JG, Chae JS, Kang KS.Recent studies have shown that mesenchymal stem cells (MSCs) are able to differentiate into multi-lineage cells such as adipocytes, chondroblasts, and osteoblasts. Amniotic membrane from whole placenta is a good source of stem cells in humans. This membrane can potentially be used for wound healing and corneal surface reconstruction. Moreover, it can be easily obtained after delivery and is usually discarded as classified waste. In the present study, we successfully isolated and characterized equine amniotic membrane-derived mesenchymal stem cells (eAM-MSCs) that were cultured and maintained i...
Van Hecke L, Magri C, Duchateau L, Beerts C, Geburek F, Suls M, Da Dalt L, Patruno M, Saunders J, Broeckx SY, Depuydt E, Spaas JH.The use of mesenchymal stem cells (MSCs) for the treatment of equine joint disease is widely investigated because of their regenerative and immunomodulatory potential. Allogeneic MSCs provide a promising alternative to autologous MSCs, since the former are immediately available and enable a thorough donor screening. However, questions have been raised concerning the immunogenic potential of allogeneic MSCs, especially after repeated administration. Methods: Current retrospective study assessed the cellular and humoral immunogenicity of ten jumping and dressage horses with naturally occurring d...
Muttini A, Salini V, Valbonetti L, Abate M.The ideal strategy for tendon healing has not been identified to date. Recently, the use of stem cells based therapy has been proposed, due to their ability to proliferate and to differentiate towards specific connective tissues lineages. Embryonic stem cells should be considered the ideal cell source for regenerative therapies, but ethical factors limit their use in humans. Mesenchymal stem cells are more easily available and can be obtained by different sources. Amnion derived stem cells can differentiate towards all three germ layers, and can be used for allogeneic transplantation and store...
Metcalf GL, McClure SR, Hostetter JM, Martinez RF, Wang C.Use of mesenchymal stem cells (MSCs) found in the stromal vascular fraction (SVF) of equine adipose tissue has promising applications for regenerative therapies. The most commonly used source of equine adipose tissue is the subcutaneous tailhead. The objective of this study was to compare 3 adipose depot sites in horses and determine the viability and cellular yield, capillary density, gene expression for selected markers, and colony-forming unit fibroblasts (CFU-Fs) in adipose tissue taken from these sites. Adipose tissue was excised from the area lateral to the tailhead, the inguinal region,...
Duan W, Chen C, Haque M, Hayes D, Lopez MJ.Use of bioscaffolds to direct osteogenic differentiation of adult multipotent stromal cells (MSCs) without exogenous proteins is a contemporary approach to bone regeneration. Identification of in vivo osteogenic contributions of exogenous MSCs on bioscaffolds after long-term implantation is vital to understanding cell persistence and effect duration. This study was designed to quantify in vivo equine MSC osteogenesis on synthetic polymer scaffolds with distinct mineral combinations 9 weeks after implantation in a murine model. Cryopreserved, passage (P)1, equine bone marrow-derived MSCs (BMSC)...
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...
Mahdavi FS, Salehi A, Seyedjafari E, Mohammadi-Sangcheshmeh A, Ardeshirylajimi A.Horses with big bone fractures have low chance to live mainly due to the lake of a proper treatment strategy. We believe that further attempts in equine bone tissue engineering will probably be required to meet all the needs for the lesion therapies. Therefore in this study we aimed to investigate the osteogenic differentiation capacity of equine adipose-derived stem cells (e-ASCs) on nano-bioactive glass (nBGs) coated poly(l-lactic acid) (PLLA) nanofibers scaffold (nBG-PLLA). Using electrospinning technique, PLLA scaffold was prepared successfully and coated with nBGs. Fabricated nanofibers w...
Schwarz C, Leicht U, Drosse I, Ulrich V, Luibl V, Schieker M, Röcken M.Adult stem cells are of particular interest for the therapeutic approach in the field of regenerative medicine. Due to their ease of harvest, adipose-derived mesenchymal stem cells (ASCs) are an attractive stem cell source that has become increasingly popular. Critical aspects of applied cell therapies are the circumstances of transport from the laboratory towards the site of operation and cell delivery into the desired area. With regard to these issues, agarose-hydrogel was analyzed as a cell carrier matrix of equine and canine ASCs in vitro, which can be used for minimally invasive applicati...
