Quintero Daniel, Perucca Orfei Carlotta, Kaplan Lee D, de Girolamo Laura, Best Thomas M, Kouroupis Dimitrios
Department of Orthopaedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL, United States.
Laboratorio di Biotecnologie Applicate all'Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
Front Bioeng Biotechnol. 2023 Jan 19;11:1040762. doi: 10.3389/fbioe.2023.1040762. eCollection 2023.
Tendinopathies encompass a highly prevalent, multi-faceted spectrum of disorders, characterized by activity-related pain, compromised function, and propensity for an extended absence from sport and the workplace. The pathophysiology of tendinopathy continues to evolve. For decades, it has been related primarily to repetitive overload trauma but more recently, the onset of tendinopathy has been attributed to the tissue's failed attempt to heal after subclinical inflammatory and immune challenges (failed healing model). Conventional tendinopathy management produces only short-term symptomatic relief and often results in incomplete repair or healing leading to compromised tendon function. For this reason, there has been increased effort to develop therapeutics to overcome the tissue's failed healing response by targeting the cellular metaplasia and pro-inflammatory extra-cellular environment. On this basis, stem cell-based therapies have been proposed as an alternative therapeutic approach designed to modify the course of the various tendon pathologies. Mesenchymal stem/stromal cells (MSCs) are multipotent stem cells often referred to as "medicinal signaling cells" due to their immunomodulatory and anti-inflammatory properties that can produce a pro-regenerative microenvironment in pathological tendons. However, the adoption of MSCs into clinical practice has been limited by FDA regulations and perceived risk of adverse events upon infusion . The introduction of cell-free approaches, such as the extracellular vesicles of MSCs, has encouraged new perspectives for the treatment of tendinopathies, showing promising short-term results. In this article, we review the most recent advances in MSC-based and MSC-derived therapies for tendinopathies. Preclinical and clinical studies are included with comment on future directions of this rapidly developing therapeutic modality, including the importance of understanding tissue loading and its relationship to any treatment regimen.
肌腱病是一类高度常见、具有多方面特征的疾病，其特点是与活动相关的疼痛、功能受损，以及有长期无法参加运动和工作的倾向。肌腱病的病理生理学仍在不断演变。几十年来，它主要与重复性过载创伤有关，但最近，肌腱病的发病已归因于组织在亚临床炎症和免疫挑战后愈合失败（愈合失败模型）。传统的肌腱病治疗只能提供短期的症状缓解，而且往往导致不完全修复或愈合，从而导致肌腱功能受损。因此，人们加大了开发治疗方法的力度，通过针对细胞化生和促炎细胞外环境来克服组织的愈合失败反应。在此基础上，基于干细胞的疗法已被提出作为一种替代治疗方法，旨在改变各种肌腱病变的病程。间充质干/基质细胞（MSCs）是多能干细胞，由于其免疫调节和抗炎特性，常被称为“药用信号细胞”，可以在病理性肌腱中产生促再生微环境。然而，MSCs在临床实践中的应用受到了美国食品药品监督管理局（FDA）法规的限制，以及输注后不良事件的潜在风险。无细胞方法的引入，如MSCs的细胞外囊泡，为肌腱病的治疗带来了新的视角，显示出了有前景的短期效果。在本文中，我们回顾了基于MSCs和源自MSCs的肌腱病治疗的最新进展。纳入了临床前和临床研究，并对这种快速发展的治疗方式的未来方向进行了评论，包括理解组织负荷及其与任何治疗方案关系的重要性。
