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

肌腱疾病通常伴随着退行性改变，这使得它在马的实践中以及人类骨科手术中都是一个治疗挑战。为了改善传统治疗效果差的临床效果，基于再生医学的治疗方法已经被探索了几年。特别是在马的实践中，多能间充质基质细胞的局部应用得到了广泛的应用，也是许多研究项目的重点。然而，仍然没有临床研究能够充分证实这种治疗方法的有效性，因此这种治疗方法的证据很少。此外，在临床环境中，尽管所使用的基质细胞群体的异质性以及细胞特性对于临床结果的治疗安全性和可重复性的重要性，但应用细胞的特性常常被忽视。因此，拟议的项目的目的是建立一个对照临床试验的基础，该基础将允许对细胞治疗的有效性进行客观评估，并将在未来进行循证治疗推荐。为了实现这一目标，将进行一项对照、随机、三盲试点研究(每个治疗组12只动物)。它将包括同种异体脂肪来源的基质细胞的标准化恢复和特征，以及标准化治疗制度，并在12个月期间进行定期后续检查，涉及两所大学兽医诊所。后续检查包括常规诊断，如临床和超声检查，以及创新的非侵入性技术，如步态分析、超声组织定征和低场磁共振成像，以获得定量的意外参数。所获得的数据将接受探索性数据分析，并作为最终临床试验的生物识别计划的基础。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，以便能够客观地评估细胞疗法对马腱疾病的疗效。因此，拟议的项目对临床兽医学具有直接的临床意义。此外，它还有助于人类医学中再生疗法的发展。

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.