Therapeutic use of stem cells in horses: Which type, how, and when? (original) (raw)
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Evidence Supporting Intralesional Stem Cell Therapy to Improve Equine Flexor Tendon Healing
Veterinary Evidence, 2017
This Knowledge Summary addresses the published information supporting intralesional administration of cell-based therapies for the treatment of flexor tendinitis/tendinopathy in horses. The current body of evidence supports intralesional stem cell therapy to improve quality of repair tissue during equine SDFT healing, based on histological and histomorphometric analyses and, in some studies, tensile load testing. Accepting this, comparative analyses to determine relative efficacies of specific cell sources are inadequate to draw any firm conclusions on this issue and any informative meta-analysis of the existing studies is confounded by inconsistencies in cell sources, injury models and clinical case selections, times after injury when cells were injected, number of cells administered, delivery vehicles used, the outcomes used to assess utility and timing of outcomes after administration. Further, in none of the experimental studies were the horses subject to training and/or racing ...
Effect of the application of stem cells for tendon injuries in sporting horses
Archivos de medicina veterinaria, 2012
RESUMEN La solución para las tendinitis sufridas por los equinos deportivos ha sido, por años, el dilema de los médicos veterinarios que se dedican a tratar este tipo de lesiones. La medicina regenerativa, utilizando células madre del mismo paciente, surge como un método innovador que permite atravesar la barrera de resolución mantenida en el tiempo y con ventajas que superan a las terapias tradicionales, que no proporcionan una recuperación total. Se han descrito la médula ósea y el tejido adiposo como fuentes principales de extracción de células madre. Ambos conllevan un proceso distinto de concentración celular que finalmente termina como un producto que debe ser inyectado en el tendón afectado y, dadas las características típicas de lesión núcleo presentadas en el tejido dañado, puede ser depositado en el centro de éste. El resultado esperado es la regeneración del tendón, sin exceso de tejido fibroso, observando alineación de las fibras tendíneas, disminución de la infiltración inflamatoria y zona hemorrágica. Con un programa de rehabilitación que incluya reposo y ejercicio progresivo, el equino vuelve a su estado competitivo óptimo. La factibilidad de realizar esta terapia en nuestra ubicación geográfica es posible, ya que la técnica de extracción desde ambas fuentes es simple y dentro de las opciones de concentración celular, siendo la del tejido adiposo más sencilla ya que requiere menos elementos y menor tiempo, ejecutándose la terapia en la etapa aguda de la lesión. La utilización de células madre en equinos es un tema de investigación creciente, que promete resultados alentadores.
The Veterinary Journal, 2018
Since the clinical use of mesenchymal stem cells (MSCs) for treating musculoskeletal injuries is gaining popularity, practitioners should be aware of the factors that may affect MSCs from tissue harvesting for MSC isolation to cell delivery into the injury site. This review provides equine practitioners with up-todate, practical knowledge for the treatment of equine patients using MSCs. A brief overview of laboratory procedures affecting MSCs is provided, but the main focus is on shipping conditions, routes of administration, injection methods, and which commonly used products can be combined with MSCs and which products should be avoided as they have deleterious effects on cells. There are still several knowledge gaps regarding MSC-based therapies in horses. Therefore, it is important to properly manage the factors which are currently known to affect MSCs, to further strengthen the evidence basis of this treatment.
Stem Cells and Development, 2019
Degenerative joint disease is one of the main causes of equine early retirement from pleasure riding or a performance career. The disease is initially triggered by an abnormal loading of normal cartilage or a normal loading of abnormal cartilage. This primary insult is accompanied with joint inflammation, which leads to further progressive degeneration of the articular cartilage and changes in the surrounding tissues. Therefore, in search for an effective treatment, 75 adult horses with early signs of degenerative fetlock joint disease were enrolled in a randomized, multicenter, double-blinded, and placebo-controlled study. Fifty animals were injected intra-articularly with the investigational veterinary product (IVP) consisting of allogeneic chondrogenic induced mesenchymal stem cells (ciMSCs) with equine allogeneic plasma, and 25 horses were injected with 0.9% NaCl (saline) control product. From week 3 to 18 after treatment, lameness scores (P < 0.001), flexion test responses (P < 0.034), and joint effusion scores (P < 0.001) were remarkably superior in IVP-treated horses. Besides nasal discharge in both treatment groups, no adverse events were observed during the entire study period. On long-term follow-up (1 year), significantly more investigational product-treated horses were working at training level or were returned to their previous level of work (P < 0.001).
Cytotherapy, 2011
Background aims. The development of an allogeneic mesenchymal stem cell (MSC) product to treat equine disorders would be useful; however, there are limited in vivo safety data for horses. We hypothesized that the injection of self (autologous) and non-self (related allogeneic or allogeneic) MSC would not elicit signifi cant alterations in physical examination, gait or synovial fl uid parameters when injected into the joints of healthy horses. Methods . Sixteen healthy horses were used in this study. Group 1 consisted of foals ( n ϭ 6), group 2 consisted of their dams ( n ϭ 5) and group 3 consisted of half-siblings ( n ϭ 5) to group 1 foals. Prior to injection, MSC were phenotyped. Placentally derived MSC were injected into contralateral joints and MSC diluent was injected into a separate joint (control). An examination, including lameness evaluation and synovial fl uid analysis, was performed at 0, 24, 48 and 72 h post-injection. Results . MSC were major histocompatibility complex (MHC) I positive, MHC II negative and CD86 negative. Injection of allogeneic MSC did not elicit a systemic response. Local responses such as joint swelling or lameness were minimal and variable. Intra-articular MSC injection elicited marked infl ammation within the synovial fl uid (as measured by nucleated cell count, neutrophil number and total protein concentration). However, there were no signifi cant differences between the degree and type of infl ammation elicited by self and non-self-MSC. Conclusions. The healthy equine joint responds similarly to a single intra-articular injection of autologous and allogeneic MSC. This pre-clinical safety study is an important fi rst step in the development of equine allogeneic stem cell therapies.
Mesenchymal Stem Cell Therapy for Equine Tendinitis
2013
Tendinitis is an important disease that leads to lameness and decreased performance in equine athletes and results in high costs associated with therapy due to a long recovery period and a high rate of recurrence. Although several treatments for equine tendinitis have been described, few are effective in significantly improving the quality of the extracellular matrix and reducing the rate of recurrence. The use of cell therapy with mesenchymal stem cells (MSCs) derived from various sources has received much attention because of its therapeutic potential for equine tendinitis. In this paper, we review patents on stem cell therapy and the specific use of MSCs for the treatment of equine tendinitis.
Regenerative Therapy for Equine Osteoarthritis: A Concise Review
Osteoarthritis (OA) is a common cause of lameness in equine and a potential cause of wastage of valuable animals. Furthermore, horse is the ideal large animal model for the preclinical study of cell-based therapy in human joints. In contrast to the drug therapy, regenerative therapy promotes the body’s own healing, restoring the structural architecture and biomechanical function of the injured tissue. Therefore, regenerative therapy field in veterinary medicine continues to evolve rapidly both experimentally and clinically. As the field of regenerative therapy continues to advance, equine practitioners need contemporary information regarding the choice of regenerative biologic type and recommendations regarding clinical implementation of regenerative therapies. Meanwhile, clinicians must also be aware of the limitation in the available knowledge regarding regenerative therapy and the impending regulatory laws that may limit its use in clinical joint diseases in equine. Although, preliminary data generated from clinical trials in human patients and experimental studies in equine osteoarthritis are encouraging, preliminary data have been published about very limited clinical application of regenerative therapies in horses suffering from clinical joint disease and the commercialization of these treatments may be premature. Additional studies are needed to determine the optimum conditions for harvest, culture and expansion of these biologics, appropriate dosing, optimal delivery method, short and long term safety. This review describes the three main biologics used for regenerative therapy, namely; stem cells, Platelet Rich Plasma (PRP) and Autologous Conditioned Serum (ACS) and draws together research findings from in vitro and in vivo studies to give an overview of current regenerative therapies for treatment of osteoarthritis in equine.
International Journal of Molecular Sciences
Osteoarthritis (OA) is a significant cause of pain in both humans and horses with a high socio-economic impact. The horse is recognized as a pertinent model for human OA. In both species, regenerative therapy with allogeneic mesenchymal stem cells (MSCs) appears to be a promising treatment but, to date, no in vivo studies have attempted to compare the effects of different cell sources on the same individuals. The objective of this study is to evaluate the ability of a single blinded intra-articular injection of allogeneic bone-marrow (BM) derived MSCs and umbilical cord blood (UCB) derived MSC to limit the development of OA-associated pathological changes compared to placebo in a post-traumatic OA model applied to all four fetlock joints of eight horses. The effect of the tissue source (BM vs. UCB) is also assessed on the same individuals. Observations were carried out using clinical, radiographic, ultrasonographic, and magnetic resonance imaging methods as well as biochemical analy...
Characterization and clinical application of mesenchymal stem cells from equine umbilical cord blood
Journal of Veterinary Science, 2013
Tendinitis of the superficial digital flexor tendon (SDFT) is a significant cause of lameness in horses; however, recent studies have shown that stem cells could be useful in veterinary regenerative medicine. Therefore, we isolated and characterized equine umbilical cord blood mesenchymal stem cells (eUCB-MSCs) from equine umbilical cord blood obtained from thoroughbred mares during the foaling period. Horses that had tendinitis of the SDFT were treated with eUCB-MSCs to confirm the therapeutic effect. After eUCB-MSCs transplantation, the core lesion in the SDFT was found to decrease. These results suggest that transplantation using eUCB-MSCs could be another source of cell treatment.
Stem cell research & therapy, 2015
Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are primarily isolated from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objectives of this study were to determine safety and lymphocyte response to multiple allogeneic IV injections of either AT-MSCs or BM-MSCs to healthy horses. We injected 3 doses of 25 x 10(6) allogeneic MSCs from either AT or BM (a total of 75 x 10(6) MSCs per horse) into 5 and 5, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response including total leukocytes numbers, serum cytokine concentration and splenic lymphocyte subsets. Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in inc...