Institute for Preclinical Sciences, University of Ljubljana, Ljubljana, Slovenia.
Adv Exp Med Biol. 2022;1401:23-55. doi: 10.1007/5584_2022_717.
Cartilage is an avascular tissue with a limited rate of oxygen and nutrient diffusion, resulting in its inability to heal spontaneously. Articular cartilage defects eventually lead to osteoarthritis (OA), the endpoint of progressive destruction of cartilage. In companion animals, OA is the most common joint disease, and many pain management and surgical attempts have been made to find an appropriate treatment. Pain management of OA is usually the first choice of OA therapy, which is often managed with nonsteroidal anti-inflammatory drugs (NSAIDs). To avoid known negative side effects of NSAIDs, other approaches are being considered, such as the use of anti-nerve growth factor monoclonal antibodies (anti-NGF mAB), hyaluronic acid (HA), platelet-rich plasma (PRP), and mesenchymal stem cells (MSCs). The latter is increasingly being recognized as effective in reducing or even eliminating pain and lameness associated with OA. However, the in vivo mechanisms of MSC action do not relate to their differentiation potential, but rather to their immunomodulatory functions. Achieving actual regeneration of cartilage to prevent OA from developing or even revert already existing OA condition has not yet been achieved. Several techniques have been tried to overcome cartilage's inability to regenerate, from osteochondral transplantation, autologous chondrocyte implantation (ACI), and matrix-induced ACI (MACI). Combinatory use of MSCs unique features and biomaterials is also being investigated with the aim to as much as possible recapitulate the native microenvironment of the cartilage, yet so far none of the methods have produced reliable and truly effective results. Although OA, for now, remains an incurable disease, novel techniques are being developed, rendering hope for the future accomplishment of actual cartilage regeneration. The aim of this chapter is firstly to summarize known and developing pain management options for OA, secondly to present surgical attempts to regenerate articular cartilage, and finally to present the attempts to improve existing regenerative treatment options using mesenchymal stem cells, with the vision for the possible use of developing strategies in veterinary medicine.
软骨是一种无血管组织，其氧气和营养物质扩散速度有限，因此无法自行愈合。关节软骨缺损最终会导致骨关节炎（OA），这是软骨进行性破坏的终点。在伴侣动物中，OA 是最常见的关节疾病，已经尝试了许多疼痛管理和手术方法来寻找合适的治疗方法。OA 的疼痛管理通常是 OA 治疗的首选，通常通过使用非甾体抗炎药（NSAIDs）来进行管理。为了避免 NSAIDs 的已知负面副作用，正在考虑其他方法，例如使用抗神经生长因子单克隆抗体（anti-NGF mAB）、透明质酸（HA）、富含血小板的血浆（PRP）和间充质干细胞（MSCs）。后者越来越被认为可以有效减轻甚至消除与 OA 相关的疼痛和跛行。然而，MSC 作用的体内机制与其分化潜力无关，而是与其免疫调节功能有关。尚未实现实际的软骨再生以防止 OA 发展，甚至逆转已经存在的 OA 状况。已经尝试了几种技术来克服软骨无法再生的问题，包括骨软骨移植、自体软骨细胞移植（ACI）和基质诱导的 ACI（MACI）。还在研究 MSC 独特特性和生物材料的组合使用，目的是尽可能再现软骨的天然微环境，但迄今为止，没有一种方法产生了可靠且真正有效的结果。虽然 OA 目前仍然是一种无法治愈的疾病，但正在开发新的技术，为未来实现真正的软骨再生带来希望。本章的目的首先是总结已知和正在开发的 OA 疼痛管理选择，其次是介绍再生关节软骨的手术尝试，最后是介绍使用间充质干细胞改善现有再生治疗选择的尝试，以期在兽医医学中可能使用正在开发的策略。
