Mesenchymal stem cells and insulin‐like growth factor‐I gene‐enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons

Schnabel, Lauren V.; Lynch, Maureen E.; Meulen, Marjolein C. H. van der; Yeager, Amy E.; Kornatowski, Matthew A.; Nixon, Alan J.

doi:10.1002/jor.20887

Cited by 223 publications

(246 citation statements)

References 48 publications

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“…A combination of both autologous MSCs and platelet derived GFs, locally administrated, could be a valid solution in order to further increase the potential of these techniques, enhancing synergically the regenerative process as suggested by some recent studies [15,16].…”

Section: Introductionmentioning

confidence: 99%

Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses

Torricelli

Fini

Filardo

et al. 2011

International Orthopaedics (SICOT)

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Purpose Tissue repair in musculoskeletal injuries is often a slow and sometimes incomplete process. Regenerative medicine based on the use of growth factors (GFs) and cell therapy is aimed at improving the quality and speed of tendon and ligament healing. The aim of this study was to evaluate the potential for the administration of a combination of autologous platelet-rich plasma (PRP) and freshly isolated bone marrow mononucleated cells (BMMNCs) in 13 competition horses affected by overuse musculoskeletal injuries (suspensory ligament desmopathy and superficial flexor tendinopathy) and refractory to other therapies. Methods After ultrasonographic localisation of the lesion, the autologous BMMNC suspension and PRP were injected directly into the core lesion. BMMNC and platelet count as well as growth factors in PRP were measured to determine factors influencing the clinical outcome. Results Horses showed a marked improvement in their degree of lameness and 84.6% were able to return to competition. Among all the factors studied, the platelet concentration predicted the healing time: significantly faster recovery (p= 0.049) was observed in cases of PRP with more than 750× 10 3 /μl platelets. Conclusions Competition horses are involved in highly demanding activities, thus being a similar model for the high mechanical overload typical of human athletes. The promising results obtained suggest that this combined biological approach may be useful even for the treatment of recalcitrant overuse musculoskeletal injuries in highly demanding patients if the appropriate dose of cells and GFs is applied.

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Section: Introductionmentioning

confidence: 99%

Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses

Torricelli

Fini

Filardo

et al. 2011

International Orthopaedics (SICOT)

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“…Using the horse as a model in clinical and experimental studies, promising results have been obtained with the therapeutical usage of MSCs for orthopedic disorders. In particular, MSC treatment of equine tendinopathy yielded lower re-injury rates (23)(24)(25)(26) and an improved tendon structure (27)(28)(29). Therefore, the therapeutic results achieved in equine athletes during the last decade could be valuable in human medicine as well.…”

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confidence: 99%

Comparative immunophenotyping of equine multipotent mesenchymal stromal cells: An approach toward a standardized definition

et al. 2014

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Horses are an approved large animal model for therapies of the musculoskeletal system. Especially for tendon disease where cell-based therapy is commonly used in equine patients, the translation of achieved results to human medicine would be a great accomplishment. Immunophenotyping of equine mesenchymal stromal cells (MSCs) remains the last obstacle to meet the criteria of the International Society for Cellular Therapy (ISCT) definition of human MSCs. Therefore, the surface antigen expression of CD 29, CD 44, CD 73, CD 90, CD 105, CD 14, CD 34, CD 45, CD 79a, and MHC II in equine MSCs from adipose tissue, bone marrow, umbilical cord blood, umbilical cord tissue, and tendon tissue was analyzed using flow cytometry. Isolated cells from the different sources and donors varied in their expression pattern of MSC-defining antigens. In particular, CD 90 and 105 showed most heterogeneity. However, cells from all samples were robustly positive for CD 29 and CD 44, while being mostly negative for CD 73 and the exclusion markers CD 14, CD 34, CD 45, CD 79a and MHC II. Furthermore, it was evident that enzymes used for cell detachment after in vitro-culture affected the detection of antigen expression. These results emphasize the need of standardization of MSC isolation, culturing, and harvesting techniques. As the equine MSCs did not meet all criteria the ISCT defined for human MSCs, further investigations for a better characterization of the cell type should be conducted. V C 2014 International Society for Advancement of Cytometry

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“…Well known method is the use of MSCs in tendinopathy of racehorses, particularly in the treatment of partial tendon injury where the therapy with MSCs have a significant impact on the ability of animals to return to the racing [32]. Schnabel et al [33] presented an in vivo study at the horses, in which the partial rupture of musculus flexor digitorum superficialis tendon was formed, and into which the concentrate of MSCs 10 × 10 (6) was applied. Ultrasound control was performed at 0, 2, 4, 6 and 8 weeks after the application.…”

Section: Research Papermentioning

confidence: 99%

Mesenchymal stem cells in the reconstruction surgery of the supraspinatus muscle lesions

Šmíd¹,

Komzák²,

Hart³

et al. 2017

Clinical-Investigation

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Background: The objective of the study was to demonstrate the effect of concentrated bone marrow stem cells (MSCs) to the healing of sutured tendon of the supraspinatus muscle in comparison to the same procedure performed without MSCs. We have postulated the hypothesis that MSCs enhance the healing of the sutured supraspinatus tendon to its humeral footprint. Methods and findings:None of the patients had to be excluded from our prospective randomized study. 50 patients met the indication criteria for isolated supraspinatus surgery. 25 patients (Group I) received MSCs into the supraspinatus footprint. 25 patients (Group II) was treated without the use of MSCs. Patients were examined pre-operatively, 6, 12 and 24 months after the surgery and assessment included physical examination, visual analogue scale (VAS), ASES (American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form) and Constant score. Patients underwent MRI 2 years postoperatively. Findings were compared with the preoperative results.We have found no statistically significant differences between both groups pre-operatively. After a 24-month follow-up period there were significant differences observed in all clinical outcomes. When compared results between both groups two years postoperatively, p-value (p=0.05) for the VAS score was 0.0176 and for the Constant score 0.0355. The only statistically non-significant was p-value for the ASES score comparing results from both groups at two years follow-up (p=0.085). The MRI findings at 2 years showed fully healed tissue of the rotator cuff tendon in 17 patients in the Group I, but only in 9 patients in the Group II. Conclusions:We have accepted the hypothesis that MSCs enhance the healing of the sutured supraspinatus tendon to its humeral footprint.

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Mesenchymal stem cells and insulin‐like growth factor‐I gene‐enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons

Cited by 223 publications

References 48 publications

Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses

Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses

Comparative immunophenotyping of equine multipotent mesenchymal stromal cells: An approach toward a standardized definition

Mesenchymal stem cells in the reconstruction surgery of the supraspinatus muscle lesions

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