Intralesional treatment of natural equine tendon disease with adipose derived mesenchymal stromal cells- controlled pilot study assessing the effect on the healing process

肌腱疾病通常伴有退行性改变，使其成为马的治疗挑战以及人类骨科手术。为了改善常规治疗后观察到的不良临床结果，基于再生医学的治疗方法已经追求了几年。特别是在马的实践中，多能间充质间质细胞的局部应用正得到广泛的应用，并成为许多研究项目的重点。然而，目前还没有临床研究能够充分证实这种治疗方法的有效性，因此这种治疗方法是在很少证据的基础上进行的。此外，在临床环境中，尽管使用的基质细胞群体具有异质性，并且细胞特性对治疗安全性和临床结果的可重复性具有重要意义，但应用细胞的特性往往被忽视。因此，拟议项目的目的是为对照临床试验建立基础，这将允许对细胞疗法的疗效进行客观评估，并允许在未来提出基于证据的治疗建议。为了实现这一目标，将进行一项对照、随机、三盲先导研究（每个治疗组12只动物）。它将包括同种异体脂肪来源基质细胞的标准化恢复和特征，以及标准化的治疗方案，包括为期12个月的定期随访检查，两所大学的兽医诊所参与其中。后续检查包括常规诊断，如临床和超声评估，以及创新的非侵入性技术，如步态分析，超声组织表征和低场磁共振成像，以获得定量的结果参数。获得的数据将进行探索性数据分析，并作为最终临床试验的生物计量学计划的基础。后者将包括明确的主要终点，并涉及更多的诊所和更多的病例，以便客观评估细胞疗法对马肌腱疾病的疗效。因此，本课题对临床兽医学具有直接的临床意义。此外，它有助于人类医学再生疗法的发展。

Tendon disease is commonly accompanied by degenerative changes, making it a therapeutic challenge in equine practice as well as human orthopedic surgery. Aiming to improve the poor clinical results that are observed following conventional treatment, therapeutic approaches based on regenerative medicine have been pursued for several years. Particularly in equine practice, the local application of multipotent mesenchymal stromal cells is being widely used and represents the focus of many research projects.However, there is still no clinical study which could adequately confirm the efficacy of this therapeutic approach, hence the treatment is being performed based on very little evidence. Furthermore, in clinical settings, characterization of the applied cells is often neglected, despite the heterogeneity of the stromal cell populations used and the major importance of the cell characteristics with respect to therapeutic safety and repeatability of clinical results.Therefore, the aim of the proposed project is to establish a basis for a controlled clinical trial, which will allow an objective assessment of the efficacy of the cell therapy and which will permit an evidence-based therapy recommendation in the future. To achieve this goal, a controlled, randomized, triple-blind pilot study (12 animals per treatment group) will be performed. It will include a standardized recovery and characterization of allogeneic adipose derived stromal cells as well as a standardized treatment regime with regular follow-up examinations over a period of 12 months, with two university veterinary clinics being involved. Follow-up examinations comprise routine diagnostics such as clinical and ultrasonographic assessment as well as innovative non-invasive techniques such as gait analysis, ultrasonographic tissue characterization and low-field magnetic resonance imaging in order to obtain quantitative outcme parameters.The data obtained will be subjected to an explorative data analysis and used as a basis for the biometrical planning of a final clinical trial. The latter will include defined primary endpoints and involve further clinics and a higher number of cases in order to enable an objective evaluation of the efficacy of the cell therapy for tendon disease in horses. Thus, the proposed project is of direct clinical relevance for clinical veterinary medicine. Furthermore, it contributes to the development of regenerative therapies in human medicine.