Therapeutic use of stem cells in horses: Which type, how, and when?

Schnabel, Lauren V.; Fortier, Lisa A.; McIlwraith, C. Wayne; Nobert, Karl M.

doi:10.1016/j.tvjl.2013.04.018

Cited by 80 publications

(69 citation statements)

References 40 publications

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“…In the horse, the past decade saw a dramatic increase in the use of MSC preparations [1,2], in particular for repair of musculoskeletal injuries [3–6], whereby conventional treatments have limited efficacy. The main clinical application of equine MSCs has been tendon and ligament repair [7–10], but other conditions such as joint disease and laminitis are also being considered [11]. Importantly, because musculoskeletal pathophysiology in horses resembles that in humans, the U.S. Food and Drug Administration has approved the use of horses as a large animal preclinical model, which broadens the relevance of the findings obtained in equine.…”

Section: Introductionmentioning

confidence: 99%

Equine Mesenchymal Stromal Cells Retain a Pericyte-Like Phenotype

Esteves

Sheldrake

Dawson

et al. 2017

Stem Cells and Development

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Mesenchymal stem/stromal cells (MSCs) have been used in human and equine regenerative medicine, and interest in exploiting their potential has increased dramatically over the years. Despite significant effort to characterize equine MSCs, the actual origin of these cells and how much of their native phenotype is maintained in culture have not been determined. In this study, we investigated the relationship between MSCs, derived from adipose tissue (AT) and bone marrow (BM), and pericytes in the horse. Both pericyte (CD146, NG2, and αSMA) and MSC (CD29, CD90, and CD73) markers were detected in equine AT and colocalized around blood vessels. Importantly, as assessed by flow cytometry, both pericyte (CD146, NG2, and αSMA) and MSC (CD29, CD44, CD90, and CD105) markers were present in a majority (≥90%) of cells in cultures of AT-MSCs and BM-MSCs; however, levels of pericyte markers were variable within each of those populations. Moreover, the expression of pericyte markers was maintained for at least eight passages in both AT-MSCs and BM-MSCs. Hematopoietic (CD45) and endothelial (CD144) markers were also detected at low levels in MSCs by quantitative polymerase chain reaction (qPCR). Finally, in coculture experiments, AT-MSCs closely associated with networks produced by endothelial cells, resembling the natural perivascular location of pericytes in vivo. Our results indicate that equine MSCs originate from perivascular cells and moreover maintain a pericyte-like phenotype in culture. Therefore, we suggest that, in addition to classical MSC markers, pericyte markers such as CD146 could be used when assessing and characterizing equine MSCs.

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Section: Introductionmentioning

confidence: 99%

Equine Mesenchymal Stromal Cells Retain a Pericyte-Like Phenotype

Esteves

Sheldrake

Dawson

et al. 2017

Stem Cells and Development

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“…The best medium for MSCs suspension at therapy time remains unknown. Some studies use the supernatant of the bone marrow or the PC for the suspension of MSCs from bone marrow (SCHNABEL et al, 2013). There is the belief that the bone marrow supernatant has beneficial effect when it is used along with the progenitor cells (SMITH; WEBBON, 2005).…”

Section: Svf and Admscs In The Equine Tendinitis Treatmentmentioning

confidence: 99%

“…At first, it was recommended to treat the tendon after the inflammatory phase and before the formation of fibrosis, i.e., during the proliferative phase, between 10 and 45 days after the emergence of the injury . However, based on the anti-inflammatory effects and on the ability of stem cells to modulate tissue repair and to regenerate through endogenous cellular recruiting and trophic factors production, the early therapy may be advantageous (SCHNABEL et al, 2013;WATTS, 2014). By taking into consideration the time needed to isolate and expand the AdMSCs (2 weeks), it would be impossible instituting the therapy using autologous progenitor cells in the initial phase; therefore, it would be more important using the allogenic AdMSCs.…”

Section: Svf and Admscs In The Equine Tendinitis Treatmentmentioning

confidence: 99%

Adipose tissue as mesenchymal stem cells source in equine tendinitis treatment

Carvalho

Hussni

Alves

2016

SCA

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Tendinitis is an important high-relapse-rate disease, which compromises equine performance and may result in early athletic life end to affected animals. Many therapies have been set to treat equine tendinitis; however, just few result in improved relapse rates, quality of extracellular matrix (ECM) and increased biomechanical resistance of the treated tissue. Due to advances in the regenerative medicine, promising results were initially obtained through the implantation of mesenchymal stem cells (MSC) derived from the bone marrow in the equine tendon injury. Since then, many studies have been using MSCs from different sources for therapeutic means in equine. The adipose tissue has appeared as feasible MSC source. There are promising results involving equine tendinitis therapy using mesenchymal stem cells from adipose tissue (AdMSCs). Keywords: Tendon. Therapy. Stem cells. Regenerative medicine. ResumoA tendinite é uma importante afecção com alta taxa de recidivas que compromete o desempenho de equinos e pode resultar no término precoce da vida atlética dos animais acometidos. Diversas terapias têm sido estabelecidas para o tratamento da tendinite equina, no entanto poucas resultam na melhora da taxa de recidiva, melhora da qualidade da matriz extracelular (MEC) e aumento da resistência biomecânica do tecido tratado. Com o advento da medicina regenerativa resultados promissores foram inicialmente obtidos com o implante de células tronco mesenquimais (CTMs) derivadas da medula óssea na lesão tendínea de equinos. Desde então, diversos estudos têm sido conduzidos utilizando CTMs de diferentes fontes para esta finalidade terapêutica em equinos. O tecido adiposo tem se mostrado como uma fonte viável de CTMs e também há resultados promissores envolvendo a terapia da tendinite equina utilizando as células tronco mesenquimais derivadas do tecido adiposo (AdCTMs). Neste artigo, dados relacionados ao uso das AdCTMs na terapia da tendinite equina serão revisados. Palavras-chave: Tendão. Terapia. Células tronco. Medicina regenerativa.

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“…BM-MSCs are commonly used in equine practice to treat a variety of musculoskeletal injuries [16]. While long-term clinical trials still need to be performed for many of these injuries, there is both preclinical and clinical evidence to support the use of BM-MSCs for the treatment of tendon injuries [17–21], and there is growing evidence for the treatment of other soft tissue injuries including meniscal injuries [22].…”

Section: Introductionmentioning

confidence: 99%

Effect of bone marrow-derived mesenchymal stem cells and stem cell supernatant on equine corneal wound healing in vitro

et al. 2017

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BackgroundWe aimed to determine and compare the in vitro effects of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) and mesenchymal stem cell supernatant (MSC-Sp) on the wound healing capacity of equine corneal fibroblasts using a scratch assay.MethodsBone marrow aspirates and eyes were collected from normal, euthanized horses with subsequent isolation and culture of BM-MSCs and corneal stromal cells. Corneal stromal cells were culture-expanded in the culture well of transwell plates and then treated with an autologous BM-MSC suspension (dose: 2.5 × 105/100 μL media with the BM-MSCs contained within the insert well), MSC-Sp solution, or naive culture media (control) for 72 h. A linear defect in confluent cell cultures was created (i.e., corneal scratch assay) to assess the cellular closure (“healing”) over time. Three representative areas of the scratch in each culture were photographed at each time point and the scratch area was quantitated using image analysis software (ImageJ). Media from the scratches were analyzed for various growth factors using human enzyme-linked immunosorbent assay (ELISA) kits that crossreact with the horse.ResultsThere was a significant percentage decrease in the scratch area remaining in the BM-MSC and MSC-Sp groups compared to the control group. There was also a significant percentage decrease in the scratch area remaining in the BM-MSC group compared to the MSC-Sp group at 36 h post-scratch and all time points thereafter. The concentration of transforming growth factor (TGF)-β1 in the media was significantly higher in the BM-MSC group compared to the control group.ConclusionsThe significant decrease in scratch area in equine corneal fibroblast cultures treated with autologous BM-MSCs compared to MSC-Sp or control treatments suggests that BM-MSCs may substantially improve corneal wound healing in horses. MSC-Sp may also improve corneal wound healing given the significant decrease in scratch area compared to control treatments, and would be an immediately available and cost-effective treatment option.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0577-3) contains supplementary material, which is available to authorized users.

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Therapeutic use of stem cells in horses: Which type, how, and when?

Cited by 80 publications

References 40 publications

Equine Mesenchymal Stromal Cells Retain a Pericyte-Like Phenotype

Equine Mesenchymal Stromal Cells Retain a Pericyte-Like Phenotype

Adipose tissue as mesenchymal stem cells source in equine tendinitis treatment

Effect of bone marrow-derived mesenchymal stem cells and stem cell supernatant on equine corneal wound healing in vitro

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