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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.
Enhanced chondrogenic differentiation of equine bone marrow-derived mesenchymal stem cells in zirconia microwell substrata. In human cartilage tissue engineering, three-dimensional zirconia substrata have the potential advantage of producing many uniform cell clusters of controlled size without xenobiotic material, allowing easy clinical application. The objective of this study was to evaluate the possibility of using zirconia porous three-dimensional microwell substrata for chondrogenic differentiation of equine bone marrow-derived mesenchymal stem cells (BMMSCs) in vitro. In regular medium, 8 × 10, 2 × 10, and 5 × 10 equine BMMSCs from five thoroughbred horses were cultured on zirconia microwell su...
Equine adipose mesenchymal stem cells (eq-ASCs) appear to have higher potential for migration and musculoskeletal differentiation. 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...
Allogeneic vs. autologous intra-articular mesenchymal stem cell injection within normal horses: Clinical and cytological comparisons suggest safety. Allogeneic bone marrow-derived mesenchymal stem cells (BMDMSCs) could provide multiple advantages over autologous BMDMSCs, including creating an 'off-the-shelf' treatment together with the ability to control for donor variation. Objective: The objective of the study was to compare the clinical and synovial fluid response of the normal equine joint to autologous and pooled-allogeneic BMDMSCs while controlling for individual variation and joint variations in response to intra-articular injections. We hypothesised that, by controlling for individual animal and joint variation, we could identify d...
Nortropane alkaloids as pharmacological chaperones in the rescue of equine adipose-derived mesenchymal stromal stem cells affected by metabolic syndrome through mitochondrial potentiation, endoplasmic reticulum stress mitigation and insulin resistance alleviation. Equine metabolic syndrome (EMS) refers to a cluster of associated abnormalities and metabolic disorders, including insulin resistance and adiposity. The numerous biological properties of mesenchymal stem cells (MSCs), including self-renewal and multipotency, have been the subject of many in-depth studies, for the management of EMS; however, it has been shown that this cell type may be affected by the condition, impairing thus seriously their therapeutic potential. Therefore, an attempt to rescue EMS adipose-derived stem cells (ASCs) with calystegines (polyhydroxylated alkaloids) that are endow...
Comparison of the Chondrogenic Differentiation Potential of Equine Synovial Membrane-Derived and Bone Marrow-Derived Mesenchymal Stem Cells. Focal cartilage injury occurs commonly and often precipitates OA. Mesenchymal stem cells (MSCs) may be useful for repairing cartilage lesions, thereby preventing joint degeneration. Although MSCs isolated from bone marrow have been shown to have chondrogenic potential, synovial membrane-derived MSCs (SM-MSCs) may have superior chondrogenic abilities due to a common progenitor cell between synovium and cartilage. The objective of this study was to directly compare the immunophenotype, proliferative capabilities, and chondrogenic potential of equine SM-MSCs and bone marrow-derived MSCs (BM-MSCs)...
The Haematococcus pluvialis extract enriched by bioaccumulation process with Mg(II) ions improves insulin resistance in equine adipose-derived stromal cells (EqASCs). Insulin resistance (IR) is one of the characteristic features of equine metabolic syndrome (EMS). Presently, the only therapies of choice are caloric restrictions combined with mineral supplementation, which might improve insulin sensitivity. In this study we investigated the effect of Haematococcus pluvialis algae water extract enriched in bioaccumulation process in magnesium ions (Hp_Mg(II)) on equine adipose derived mesenchymal stromal stem cells, in which insulin resistance was induced by palmitic acid (IR-EqASCs). For this purpose, chemical characterization of H. pluvialis was performed w...
Intra-Articular Injection of 2 Different Dosages of Autologous and Allogeneic Bone Marrow- and Umbilical Cord-Derived Mesenchymal Stem Cells Triggers a Variable Inflammatory Response of the Fetlock Joint on 12 Sound Experimental Horses. Osteoarthritis is a significant and costly cause of pain for both humans and horses. The horse has been identified as a suitable model for human osteoarthritis. Regenerative therapy with allogeneic mesenchymal stem cells (MSCs) is a promising treatment, but the safety of this procedure continues to be debated. The aim of this study is to evaluate the safety of intra-articular injections of allogeneic MSCs on healthy joints by comparing two different dosages and two different tissue sources, namely, bone marrow and umbilical cord blood, with a placebo treatment on the same individuals. We also ...
Generation and miRNA Characterization of Equine Induced Pluripotent Stem Cells Derived from Fetal and Adult Multipotent Tissues. Pluripotent stem cells are believed to have greater clinical potential than mesenchymal stem cells due to their ability to differentiate into almost any cell type of an organism, and since 2006, the generation of patient-specific induced pluripotent stem cells (iPSCs) has become possible in multiple species. Objective: We hypothesize that different cell types respond differently to the reprogramming process; thus, the goals of this study were to isolate and characterize equine adult and fetal cells and induce these cells to pluripotency for future regenerative and translational purposes. Metho...
Adipose-Derived Stromal Vascular Fraction and Cultured Stromal Cells as Trophic Mediators for Tendon Healing. Adipose-derived stromal vascular fraction (SVF) is a heterogeneous population of cells that yields a homogeneous population of plastic-adherent adipose tissue-derived stromal cells (ASC) when culture-expanded. SVF and ASC have been used clinically to improve tendon healing, yet their mechanism of action is not fully elucidated. The objective of this study was to investigate the potential for ASC to act as trophic mediators for tendon healing. Flexor digitorum superficialis tendons and adipose tissue were harvested from adult horses to obtain SVF, ASC, and tenocytes. Growth factor gene expressi...
Glycan Profiling Analysis of Equine Amniotic Progenitor Mesenchymal Cells and Their Derived Extracellular Microvesicles. Equine amniotic mesenchymal cells (eAMCs) are involved in many mechanisms in tissue regenerative processes. Their secreted vesicles are important effectors in a wide array of biological processes, and contribute to in vivo healing of equine tendon lesions and endometrial inflammation. Glycoconjugates are involved in cellular recognition and in the efficient uptake of extracellular vesicles (EVs) by recipient cells. In this study, we evaluated the surface glycosylation pattern of eAMCs and their EVs from the eAMCs released in conditioned medium. We used a microarray procedure in which eAMCs and...
The first detection of the sequence of bacteria from the Simkaniaceae family in surface waters in Poland. One of the most common reasons for horse lameness is subchondral bone cysts (SBCs), which are especially evident in young horse athletes. It is believed that SBC development is strongly associated with an individual's bone growth and/or bone microstructure impairment. Current methods of SBC treatment include pharmacological treatment or surgical procedures which may allow the bone within the cyst to rebuild and be restored to properly developed bone tissue. Thus, we propose filling the SBCs with a 3D complex of alginate hydrogel and autologous adipose derived mesenchymal stem cells (ASCs). We ...
Analysis of mesenchymal cells (MSCs) from bone marrow, synovial fluid and mesenteric, neck and tail adipose tissue sources from equines. Mesenchymal stem cells (MSCs) have been used in equines as an alternative therapy. A comparative study about the phenotype and in vitro performance of different MSCs tissue sources in adult equines was needed. This study might serve to provide the knowledge to select a valuable harvesting source of MSCs. Bone marrow, synovial and adipose (mesenteric, neck and tail fat) tissues were collected from adult equines. Cell surface markers expression (CD11α/CD18, CD45, CD79α, CD90, CD105 and MHC II) and in vitro differentiation assays were made. In vitro cell migration, cell growth and wound healing...
The use of equine chondrogenic-induced mesenchymal stem cells as a treatment for osteoarthritis: A randomised, double-blinded, placebo-controlled proof-of-concept study. There is a need to improve therapies for osteoarthritis in horses. Objective: To assess the efficacy of equine allogeneic chondrogenic-induced mesenchymal stem cells combined with equine allogeneic plasma as a novel therapy for osteoarthritis in horses. Methods: Randomised, double-blinded, placebo-controlled experiment. Methods: In 12 healthy horses, osteoarthritis was induced in the metacarpophalangeal joint using an osteochondral fragment-groove model. Five weeks after surgery, horses were randomly assigned to either an intra-articular injection with chondrogenic-induced mesenchymal stem cel...
Hypoxia and mesenchymal stromal cells as key drivers of initial fracture healing in an equine in vitro fracture hematoma model. Fractures in horses-whether simple fractures with just one clean break, or incomplete greenstick with stress fractures, or complications such as shattered bones can all be either minimal or even catastrophic. Thus, improvement in fracture healing is a hallmark in equine orthopedics. The fracture healing process implements a complex sequence of events including the initial inflammatory phase removing damaged tissue, re-establishment of vessels and mesenchymal stromal cells, a soft and hard callus phase closing the fracture gap as well as the remodeling phase shaping the bone to a scar-free tiss...
Insights into animal models for cell-based therapies in translational studies of lung diseases: Is the horse with naturally occurring asthma the right choice? Human asthma is a widespread disease associated with chronic inflammation of the airways, leading to loss of quality of life, disability and death. Corticosteroid administration is the mainstream treatment for asthmatic patients. Corticosteroids reduce airway obstruction and improve quality of life, although symptoms persist despite treatment in many patients. Moreover, available therapies failed to reverse the lung pathology present in asthma. Animal models, mostly rats and mice, in which the disease is experimentally induced, have been studied to identify new therapeutic targets for human as...
Improved expansion of equine cord blood derived mesenchymal stromal cells by using microcarriers in stirred suspension bioreactors. Equine mesenchymal stromal cells (MSCs) are increasingly investigated for their clinical therapeutic utility. Such cell-based treatments can require cell numbers in the millions or billions, with conventional expansion methods using static T-flasks typically inefficient in achieving these cell numbers. Equine cord blood-derived MSCs (eCB-MSCs), are promising cell candidates owing to their capacity for chondrogenic differentiation and immunomodulation. Expansion of eCB-MSCs in stirred suspension bioreactors with microcarriers as an attachment surface has the potential to generate clinically rel...
Equine Adipose-Derived Mesenchymal Stromal Cells Release Extracellular Vesicles Enclosing Different Subsets of Small RNAs. Equine adipose-derived mesenchymal stromal cells (e-AdMSC) exhibit attractive proregenerative properties strongly related to the delivery of extracellular vesicles (EVs) that enclose different kinds of molecules including RNAs. In this study, we investigated small RNA content of EVs produced by e-AdMSC with the aim of speculating on their possible biological role. Methods: EVs were obtained by ultracentrifugation of the conditioned medium of e-AdMSC of 4 subjects. Transmission electron microscopy and scanning electron microscopy were performed to assess their size and nanostructure. RNA was is...
Peripheral blood-derived mesenchymal stem cells demonstrate immunomodulatory potential for therapeutic use in horses. Previously, we showed that mesenchymal stem cells (MSC) can be mobilized into peripheral blood using electroacupuncture (EA) at acupoints, LI-4, LI-11, GV-14, and GV-20. The purpose of this study was to determine whether EA-mobilized MSC could be harvested and expanded in vitro to be used as an autologous cell therapy in horses. Peripheral blood mononuclear cells (PBMC) isolated from young and aged lame horses (n = 29) showed a marked enrichment for MSCs. MSC were expanded in vitro (n = 25) and administered intravenously at a dose of 50 x 106 (n = 24). Treatment resulted in significant improve...
Evaluation of alginate hydrogel encapsulated mesenchymal stem cell migration in horses. Osteoarthritis is an incapacitating disease characterized by pain and a progressive decrease in joint mobility. The implantation of mesenchymal stem cells (MSCs) has shown promising results for its treatment. The challenge remains to keep the cells longer at the site of action, increasing their therapeutic potential. The aim of this study was to evaluate the effectiveness of the Qtracker® 655 nanocrystal marking on allogeneic synovial membrane (SM) MSCs, encapsulated in alginate hydrogel, evaluating the migration of these cells. The 10 radiocarpal joints were submitted to arthroscopic surgery...
Chondrogenic differentiation potential of adult and fetal equine cell types. To determine the chondrogenic potential of cells derived from interzone tissue, the normal progenitor of articular cartilage during fetal development, compared to that of adult bone marrow-derived and adipose-derived mesenchymal cell isolates. The objective of this study was to compare the chondrogenic potential of fetal musculoskeletal progenitor cells to adult cell types, which are currently used therapeutically to facilitate joint cartilage repair in equine clinical practice. The hypothesis tested was that cells derived from interzone tissue have a chondrogenic potential that exceeds that o...
Influence of mechanical fluid shear stress on the osteogenic differentiation protocols for Equine adipose tissue-derived mesenchymal stem cells. Cell-based therapies have become a promising approach to promote tissue regeneration and the treatment of musculoskeletal disorders. Bone regeneration maintains bone homeostasis, mechanical stability and physical performance. Mechanical stimulation showed to induce stem cell differentiation into the osteogenic fate. However, the effect of various osteogenic protocols on the osteogenic commitment of equine adipose-derived stem cells is not fully elucidated. Here we examined the influence of fluid-based shear stress (FSS) via mechanical rocking to assess whether mechanical stimulation promotes o...
Subconjunctival bone marrow-derived mesenchymal stem cell therapy as a novel treatment alternative for equine immune-mediated keratitis: A case series. Equine immune-mediated keratitis (IMMK) leads to increased corneal opacity and inflammation secondary to an alteration of the local immune system. Bone marrow-derived mesenchymal stem cells (BM-MSC) have been shown to modulate the immune system by downregulating inflammation. Four horses with unilateral IMMK poorly responsive to traditional medical treatments underwent novel, autologous subconjunctival BM-MSC therapy. Bone marrow was harvested and processed as previously described for equine orthopedic disease. Horses received autologous subconjunctival BM-MSC injections approximately every 3-...
Heterologous Wharton’s Jelly Derived Mesenchymal Stem Cells Application on a Large Chronic Skin Wound in a 6-Month-Old Filly. 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...
Exosomes isolation and identification from equine mesenchymal stem cells. Mesenchymal stem cells are used for different therapeutic approaches, e.g. for osteoarthritis, lesions of the tendon as well as for bone defects. Current research on the mechanism of stem cells on the repair of damaged tissue suggest an important role of a cell-to-cell communication through secreted extracellular vesicles, mainly represented by exosomes. To enhance the scarce knowledge on the functional role of exosomes we compared as a first step different techniques to isolate and identify exosomes from the supernatant of equine adipose derived mesenchymal stem cells for further characteriza...
Ultrasound-guided injection of the cranial tibial artery for stem cell administration in horses. A technique for intra-arterial injection of mesenchymal stem cells (MSC) has been established for front limbs with the use of the median artery. This approach has been proposed for treatment of soft tissue injuries of the equine distal limb. A technique has not been validated yet for hindlimb injection. Objective: To assess the feasibility of injection of the cranial tibial artery in horses, and to evaluate the distribution and persistence of MSC after injection. Methods: In vivo experiment. Methods: In a first phase, the cranial tibial arteries of both hindlimbs of three research horses were ...
Persistence of fluorescent nanoparticle-labelled bone marrow mesenchymal stem cells in vitro and after intra-articular injection. Mesenchymal stem cells (MSCs) improve the osteoarthritis condition, but the fate of MSCs after intra-articular injection is unclear. We used fluorescent nanoparticles (quantum dots [QDs]) to track equine MSCs (QD-labelled MSCs [QD-MSCs]) in vivo after intra-articular injection into normal and osteoarthritic joints. One week after injection of QD-MSCs, unlabelled MSCs, or vehicle, we determined the presence of QD-MSCs in synovium and articular cartilage histologically. In vitro, we evaluated the persistence of QDs in MSCs and whether QDs affected proliferation, immunophenotype, or differentiati...
Metformin Increases Proliferative Activity and Viability of Multipotent Stromal Stem Cells Isolated from Adipose Tissue Derived from Horses with Equine Metabolic Syndrome. In this study, we investigated the influence of metformin (MF) on proliferation and viability of adipose-derived stromal cells isolated from horses (EqASCs). We determined the effect of metformin on cell metabolism in terms of mitochondrial metabolism and oxidative status. Our purpose was to evaluate the metformin effect on cells derived from healthy horses (EqASC) and individuals affected by equine metabolic syndrome (EqASC). The cells were treated with 0.5 μM MF for 72 h. The proliferative activity was evaluated based on the measurement of BrdU incorporation during DNA synthesis, as well as...
Equine Cord Blood Mesenchymal Stromal Cells Have Greater Differentiation and Similar Immunosuppressive Potential to Cord Tissue Mesenchymal Stromal Cells. Mesenchymal stromal cells (MSCs) are the most common cell population studied for therapeutic use in veterinary medicine. MSCs obtained from neonatal sources such as umbilical cord tissue (CT-MSCs) or cord blood (CB-MSCs) are appealing due to the non-invasive nature of procurement and the time allowed for characterization of cells before use. However, it remains unclear as to whether CB- or CT-MSCs have equivalent progenitor and non-progenitor functions. CB-MSCs have been shown to have superior chondrogenic potential to MSCs from other sources, whereas their immunomodulatory capacity does not s...
A pilot study of regenerative therapy by implanting synovium-derived mesenchymal stromal cells in equine osteochondral defect models. Synovium-derived mesenchymal stromal cells (SM-MSCs) from seven Thoroughbreds with naturally occurring intra-articular fracture proliferated to over ten million cells by the second passage. Using three experimental Thoroughbreds, columnar osteochondral defects were made arthroscopically at the bilateral distal radius. Five million allogenic SM-MSCs were implanted into the right defect, and another five million were injected into the right radio-carpal joint (implantation site). No SM-MSCs were implanted into the left defect or the same joint (control site). At 3 and 6 weeks after surgery, ten ...
Cladophora glomerata methanolic extract decreases oxidative stress and improves viability and mitochondrial potential in equine adipose derived mesenchymal stem cells (ASCs). Reactive oxygen species (ROS) are key mediators of several cellular damage and thus associated with equine diseases such as inflammation and metabolic syndrome. This study aimed to evaluate the protective and antioxidant activities of methanolic extract prepared from Cladophora glomerata (C. glomerata) biomass, on equine adipose derived mesenchymal stem cells (EqASCs), under experimental oxidative stress induced by HO. Pre-treatment of EqASCs cells with different concentrations of C. glomerata methanolic extract (1% and 5%) provided a clear protection against cellular damage triggered by HO. T...
