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Topic:Mesenchymal Cells
Mesenchymal cells are multipotent stromal cells found in horses that have the ability to differentiate into various cell types, including osteoblasts, chondrocytes, and adipocytes. These cells are present in multiple tissues, such as bone marrow, adipose tissue, and umbilical cord blood. Mesenchymal cells contribute to tissue repair and regeneration and are involved in modulating the immune response. Their potential for differentiation and self-renewal makes them a subject of interest in regenerative medicine and therapeutic applications in equine health. This page compiles peer-reviewed research studies and scholarly articles that explore the characteristics, differentiation potential, and therapeutic applications of mesenchymal cells in horses.
Production of extracellular vesicles from equine embryo-derived mesenchymal stromal cells. Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) have shown promise as off-the-shelf therapeutics; however, producing them in sufficient quantities can be challenging. In this study, MSCs were isolated from preimplantation equine embryos and used to produce EVs in two commercially available bioreactor designs. Mesenchymal stromal cells (MSC) have recently been explored for their potential use as therapeutics in human and veterinary medicine applications, such as the treatment of endometrial inflammation and infertility. Allogeneic MSC-derived extracellular vesicles (EVs) may...
Therapeutics prior to mesenchymal stromal cell therapy improves outcome in equine orthopedic injuries. Mesenchymal stromal (stem) cells (MSCs) have been studied to treat many common orthopedic injuries in horses. However, there is limited information available on when and how to use this treatment effectively. The aim of this retrospective study is to report case features, treatment protocols, and clinical outcomes in horses treated with MSCs. Methods: 65 horses presenting with tendinous, ligamentous, and articular injuries, and treated with MSCs prepared by a single laboratory between 2016 and 2019. Outcome information was available for 26 horses. Methods: Signalment, clinical signs, diagnosti...
Comparison of Sources and Methods for the Isolation of Equine Adipose Tissue-Derived Stromal/Stem Cells and Preliminary Results on Their Reaction to Incubation with 5-Azacytidine. Physiological particularities of the equine heart justify the development of an in vitro model suitable for investigations of the species-specific equine cardiac electrophysiology. Adipose tissue-derived stromal/stem cells (ASCs) could be a promising starting point from which to develop such a cardiomyocyte (CM)-like cell model. Therefore, we compared abdominal, retrobulbar, and subcutaneous adipose tissue as sources for the isolation of ASCs applying two isolation methods: the collagenase digestion and direct explant culture. Abdominal adipose tissue was most suitable for the isolation of ASC...
Interleukin-1β in tendon injury enhances reparative gene and protein expression in mesenchymal stem cells. Tendon injury in the horse carries a high morbidity and monetary burden. Despite appropriate therapy, reinjury is estimated to occur in 50-65% of cases. Although intralesional mesenchymal stem cell (MSC) therapy has improved tissue architecture and reinjury rates, the mechanisms by which they promote repair are still being investigated. Additionally, reevaluating our application of MSCs in tendon injury is necessary given recent evidence that suggests MSCs exposed to inflammation (deemed MSC licensing) have an enhanced reparative effect. However, applying MSC therapy in this context is limited...
Functional properties of equine adipose-derived mesenchymal stromal cells cultured with equine platelet lysate. 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...
Engineered nanoparticles toxicity on adipose tissue derived mesenchymal stem cells: A preliminary investigation. Nanoscience and nanotechnologies have recently gained importance in several fields, such as industry and medicine. A big issue of the increasing application of nanomaterials is the poor literature regarding their potential toxicity in humans and animals. Recently, adult stem cells have been proposed as putative targets of nanoparticles (NPs). This study aims to investigate the effects of zerovalent-metallic NPs on isolated and amplified equine Adipose tissue derived Mesenchymal Stem Cells (eAdMSCs). Cells were treated with Cobalt (Co-), Iron (Fe-), and Nickel (Ni-) nanoparticles (NPs) at diffe...
Shipping Temperature, Time and Media Effects on Equine Wharton’s Jelly and Adipose Tissue Derived Mesenchymal Stromal Cells Characteristics. To use Mesenchymal Stromal Cells (MSCs) in equine patients, isolation and expansion are performed in a laboratory. Cells are then sent back to the veterinary clinic. The main goal of storage conditions during cell transport is to preserve their biological properties and viability. The aim of this study was to evaluate the effects of storage solutions, temperature and time on the characteristics of equine adipose tissue and Wharton's jelly-derived MSCs. We compared two different storage solutions (plasma and 0.9% NaCl), two different temperatures (4 °C and room temperature) and three time fram...
The combination of BMP12 and KY02111 enhances tendon differentiation in bone marrow-derived equine mesenchymal stromal cells (BM-eMSCs). The Wingless and Int-1 (WNT) and bone morphogenic protein/growth differentiation factor (BMP/GDF) signalling pathways contribute significantly to the development of the musculoskeletal system. The mechanism by which they contribute is as follows: BMP/GDF signalling usually promotes tendon differentiation, whereas WNT signalling inhibits it. We hypothesised that inhibiting WNT and subsequently stimulating BMP signalling may enhance the tenogenic differentiation of stem cells. The objective of this study was to determine whether a combination of WNT inhibitor (KY02111) and BMP12/GDF7 protein cou...
Heat Shock Alters the Proteomic Profile of Equine Mesenchymal Stem Cells. 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 ...
Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation. Allogenic mesenchymal stem cell (MSC) secretome is a novel intra-articular therapeutic that has shown promise in and small animal models and warrants further investigation. Unassigned: To investigate if intra-articular allogenic MSC-secretome has anti-inflammatory effects using an equine model of joint inflammation. Unassigned: Randomized positively and negatively controlled experimental study. Unassigned: In phase 1, joint inflammation was induced bilaterally in radiocarpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After 2 h, the secretome of INFy and TNFα stimul...
Effects of intravenous administration of peripheral blood-derived mesenchymal stromal cells after infusion of lipopolysaccharide in horses. A systemic and dysregulated immune response to infection contributes to morbidity and mortality associated with sepsis. Peripheral blood-derived mesenchymal stromal cells (PB-MSC) mitigate inflammation in animal models of sepsis. Allogeneic PB-MSC administered IV to horses is well-tolerated but therapeutic benefits are unknown. Objective: After IV lipopolysaccharide (LPS) infusion, horses treated with PB-MSC would have less severe clinical signs, clinicopathological abnormalities, inflammatory cytokine gene expression, and oxidative stress compared to controls administered a placebo. Methods: ...
Design of an electrospun tubular construct combining a mechanical and biological approach to improve tendon repair. Hand tendon injuries represent a major clinical problem and might dramatically diminish a patient's life quality. In this study, a targeted solution for flexor tendon repair was developed by combining a mechanical and biological approach. To this end, a novel acrylate-endcapped urethane-based polymer (AUP) was synthesized and its physico-chemical properties were characterized. Next, tubular repair constructs were developed using electrospinning of the AUP material with incorporated naproxen and hyaluronic acid (i.e. anti-inflammatory and anti-adhesion compounds, respectively), and with a tubul...
Characterisation of Extracellular Vesicles from Equine Mesenchymal Stem Cells. Extracellular vesicles (EVs) are nanosized lipid bilayer-encapsulated particles secreted by virtually all cell types. EVs play an essential role in cellular crosstalk in health and disease. The cellular origin of EVs determines their composition and potential therapeutic effect. Mesenchymal stem/stromal cell (MSC)-derived EVs have shown a comparable therapeutic potential to their donor cells, making them a promising tool for regenerative medicine. The therapeutic application of EVs circumvents some safety concerns associated with the transplantation of viable, replicating cells and facilitates...
Bone Marrow MSC Secretome Increases Equine Articular Chondrocyte Collagen Accumulation and Their Migratory Capacities. Equine osteoarthritis (OA) leads to cartilage degradation with impaired animal well-being, premature cessation of sport activity, and financial losses. Mesenchymal stem cell (MSC)-based therapies are promising for cartilage repair, but face limitations inherent to the cell itself. Soluble mediators and extracellular vesicles (EVs) secreted by MSCs are the alternatives to overcome those limitations while preserving MSC restorative properties. The effect of equine bone marrow MSC secretome on equine articular chondrocytes (eACs) was analyzed with indirect co-culture and/or MSC-conditioned media ...
Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration. Allogeneic mesenchymal stem cells (MSC) are widely used in clinical routine due to the shorter expansion time and reliability of its quality. However, some recipients can produce alloantibodies that recognize MSCs and activate the immune system, resulting in cell death. Although antibody production was already described after MSC injection, no previous studies described the immune response after intra-articular MSC injection in acute synovitis. This study aimed to evaluate the influence of inflammation on immune response after single and repeated intra-articular injections of synovial membrane...
TRPV4 activation enhances compressive properties and glycosaminoglycan deposition of equine neocartilage sheets. To evaluate the effect of Transient Receptor Potential Vanilloid 4 (TRPV4) cation channel modulation on mesenchymal stromal cell (MSC)-derived neocartilage. Unassigned: RT-PCR was performed to evaluate mRNA levels of chondrogenic, hypertrophic and candidate mechanoresponsive genes in equine neocartilage sheets exposed to pulses of the TRPV4 agonist (GSK101) at different concentrations (N = 10). Biochemical assays and mechanical tests (double indentation and unconfined compression) evaluated neocartilage properties (N = 5). Unassigned: GSK101 treatment (1 nM) increased leve...
Equine Mesenchymal Stem Cells Influence the Proliferative Response of Lymphocytes: Effect of Inflammation, Differentiation and MHC-Compatibility. Immunomodulation and immunogenicity are pivotal aspects for the therapeutic use of mesenchymal stem cells (MSCs). Since the horse is highly valuable as both a patient and translational model, further knowledge on equine MSC immune properties is required. This study analysed how inflammation, chondrogenic differentiation and compatibility for the major histocompatibility complex (MHC) influence the MSC immunomodulatory-immunogenicity balance. Equine MSCs in basal conditions, pro-inflammatory primed (MSC-primed) or chondrogenically differentiated (MSC-chondro) were co-cultured with either autolo...
MSC in Tendon and Joint Disease: The Context-Sensitive Link Between Targets and Therapeutic Mechanisms. Mesenchymal stromal cells (MSC) represent a promising treatment option for tendon disorders and joint diseases, primarily osteoarthritis. Since MSC are highly context-sensitive to their microenvironment, their therapeutic efficacy is influenced by their tissue-specific pathologically altered targets. These include not only cellular components, such as resident cells and invading immunocompetent cells, but also components of the tissue-characteristic extracellular matrix. Although numerous models have already shown potential MSC-related mechanisms of action in tendon and joint diseases, only a...
Peptide Mediated Adhesion to Beta-Lactam Ring of Equine Mesenchymal Stem Cells: A Pilot Study. 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...
Cellular and Humoral Immunogenicity Investigation of Single and Repeated Allogeneic Tenogenic Primed Mesenchymal Stem Cell Treatments in Horses Suffering From Tendon Injuries. The use of mesenchymal stem cells (MSCs) for the treatment of equine tendon disease is widely investigated because of their regenerative and immunomodulatory potential. However, questions have been raised concerning the immunogenic properties of allogeneic MSCs. Therefore, two studies were conducted to assess the safety of equine allogeneic peripheral blood-derived tenogenic primed MSCs (tpMSCs). The objective was to evaluate if a single and repeated tpMSC administration induced a cellular and humoral immune response in horses suffering from tendon injuries. Horses enrolled in the first study ...
Case Report: Repeated Intralesional Injections of Autologous Mesenchymal Stem Cells Combined With Platelet-Rich Plasma for Superficial Digital Flexor Tendon Healing in a Show Jumping Horse. In the present case report a show jumping 10-year-old Sella Italiano gelding, presented with severe lameness, swelling and pain at palpation of the mid-metacarpal region of the left forelimb. Clinical and ultrasound examination diagnosed a chronic tendonitis of the central region of the superficial digital flexor tendon (SDFT). The lesion was a reoccurrence since it developed from a previously healed injury. The horse had to stop competing and was unresponsive to gold-standard treatments as Non-steroidal anti-inflammatory drugs (NSAIDs) and conservative management after 6 months of therapy. Th...
Comparative results of 3 treatments for medial femoral condyle subchondral cystic lesions in Thoroughbred racehorses. To compare 3 different methods for treatment of medial femoral condyle (MFC) subchondral cystic lesions in Thoroughbred horses <24 months old based on the criterion of ability to race post-treatment. Methods: Retrospective cohort study. Methods: Thoroughbreds (n = 107, age < 24 months) diagnosed with MFC subchondral cystic lesions. Methods: Medical records between January 2004 and December 2017 were reviewed. Three treatment methods were used in these horses during that time frame: arthroscopic debridement, intralesional autologous mesenchymal stem cell (MSC) injection, and int...
Corrigendum: Extracorporeal Shock Wave Therapy Enhances the In Vitro Metabolic Activity and Differentiation of Equine Umbilical Cord Blood Mesenchymal Stromal Cells. [This corrects the article DOI: 10.3389/fvets.2020.554306.].
Osteochondral regeneration of the femoral medial condyle by using a scaffold-free 3D construct of synovial membrane-derived mesenchymal stem cells in horses. Medical interventions for subchondral bone cysts in horses have been extensively studied. This study investigated the regeneration of articular cartilage and subchondral bone with scaffold-free three-dimensional (3D) constructs of equine synovial membrane-derived mesenchymal stem cells (SM-MSCs) isolated from three ponies and expanded until over 1.0 × 10 cells at passage 2 (P2). Results: SM-MSCs were strongly positive for CD11a/CD18, CD44, and major histocompatibility complex (MHC) class I; moderately positive for CD90, CD105, and MHC class II; and negative for CD34 and CD45 on flow cytom...
Effect of intrabronchial administration of autologous adipose-derived mesenchymal stem cells on severe equine asthma. Severe equine asthma (SEA) is a common chronic respiratory disease and a significant health and well-being problem in horses. Current therapeutic strategies improve pulmonary function and clinical signs in some horses, but in the long-term, return to full athletic function appears to be rare. The aim of this study was to assess the safety and the effect of intrabronchial administration of adipose-derived mesenchymal stem cells (AD-MSC) on pulmonary inflammatory and clinical parameters in horses with SEA. This was a randomized controlled trial. Twenty adult horses diagnosed with SEA were random...
Platelet Lysate for Mesenchymal Stromal Cell Culture in the Canine and Equine Species: Analogous but Not the Same. Platelet lysate (PL) is an attractive platelet-based therapeutic tool and has shown promise as xeno-free replacement for fetal bovine serum (FBS) in human and equine mesenchymal stromal cell (MSC) culture. Here, we established a scalable buffy-coat-based protocol for canine PL (cPL) production (n = 12). The cPL was tested in canine adipose MSC (n = 5) culture compared to FBS. For further comparison, equine adipose MSC (n = 5) were cultured with analogous equine PL (ePL) or FBS. During canine blood processing, platelet and transforming growth factor-β1 concentrations increased ( < 0.05 and ...
In vitro antimicrobial activity of equine platelet lysate and mesenchymal stromal cells against common clinical pathogens. Septic arthritis is considered a medical emergency. Disease following bacterial colonization can lead to significant morbidity and mortality and requires costly treatment. Antimicrobial properties of regenerative therapies, including mesenchymal stromal cells and platelet products, have been researched extensively in human medicine. Although fewer studies have been conducted in veterinary species, they have shown promising results. The purpose of this study was to evaluate bacterial suppression by equine platelet lysate (EPL) and adipose-derived mesenchymal stromal cells (ASCs) in vitro. We hy...
Effect of Allogeneic Oral Mucosa Mesenchymal Stromal Cells on Equine Wound Repair. To assess the clinical value and safety of the application of allogeneic equine oral mucosa mesenchymal stromal cells (OM-MSCs) to wounds. Animals. 8 healthy adult horses without front limb skin lesions or musculoskeletal disease. Procedures. Stem cells were isolated from the oral mucosa of a donor horse. Horses were subjected to the creation of eight full-thickness cutaneous wounds, two on each distal forelimb (FL) and two on both sides of the thorax (TH). Each wound was subjected to one out of four treatments: no medication (T1), hyaluronic acid- (HA-) gel containing OM-MSC (T2), HA-gel cont...
Steps Toward Standardized In Vitro Assessment of Immunomodulatory Equine Mesenchymal Stromal Cells Before Clinical Application. Inflammation-associated disorders are significant causes of morbidity in horses. Equine single-donor mesenchymal stromal cells (sdMSCs) hold promise as cell-therapy candidates due to their secretory nonprogenitor functions. This has been demonstrated by mononuclear cell suppression assays (MSAs) showing that sdMSCs are blood mononuclear cell (BMC) suppressive in vitro. sdMSCs derived from umbilical cord blood are of clinical interest due to their ease of procurement, multipotency, and immunomodulatory ability. Due to the inherent donor-to-donor heterogeneity of MSCs, the development of robust ...
Mesenchymal Stromal Cells Adapt to Chronic Tendon Disease Environment with an Initial Reduction in Matrix Remodeling. Tendon lesions are common sporting injuries in humans and horses alike. The healing process of acute tendon lesions frequently results in fibrosis and chronic disease. In horses, local mesenchymal stromal cell (MSC) injection is an accepted therapeutic strategy with positive influence on acute lesions. Concerning the use of MSCs in chronic tendon disease, data are scarce but suggest less therapeutic benefit. However, it has been shown that MSCs can have a positive effect on fibrotic tissue. Therefore, we aimed to elucidate the interplay of MSCs and healthy or chronically diseased tendon matrix...
