Infectious Diseases and Transplantation Division, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona,
Eur Cell Mater. 2020 Aug 26;40:88-114. doi: 10.22203/eCM.v040a06.
Rheumatic diseases such as osteoarthritis (OA) are a major social and economic burden because of the population aging and the lack of curative solutions. An effective cell therapy may be the best treatment option for OA and other cartilage diseases. However, the main cellular strategy used to repair articular cartilage, the transplantation of autologous chondrocytes, is limited to a small number of patients with traumatic lesions. The use of joint replacement after years of disease progression proves the great medical need in current practice. Mesenchymal stromal/stem cells (MSCs) provide an alternative cell source for cartilage regeneration due to numerous advantages, comprising relative ease to isolate and culture, chondrogenic capacity, and anti-inflammatory effects. Initial clinical trials with MSCs have led to encouraging results, but many variables have to be considered to attain true amelioration of disease or repair (type and status of cartilage disease, source and conditions of cells, administration regime, combinatorial approaches). Particularly, allogeneic MSCs are an advantageous cellular product. The animal models chosen for preclinical evaluation are also relevant for successful translation into clinical practice. Considering the limitations in the field, rigorous comparative and validating studies in well-established animal models (including large animals) are still needed to set up the bases for additional clinical trials. The present review of studies performed in small and large animal models should help clarify the applicability of MSC-based therapies for articular cartilage repair.
风湿性疾病(如骨关节炎)是一个重大的社会和经济负担,这是由于人口老龄化和缺乏治愈方法所致。有效的细胞疗法可能是治疗骨关节炎和其他软骨疾病的最佳选择。然而,用于修复关节软骨的主要细胞策略——自体软骨细胞移植,仅限于少数创伤性病变的患者。随着疾病的多年进展,关节置换的应用证明了当前实践中的巨大医疗需求。间充质基质/干细胞(MSCs)由于具有许多优势,如相对容易分离和培养、软骨生成能力和抗炎作用,为软骨再生提供了另一种细胞来源。MSCs 的初步临床试验取得了令人鼓舞的结果,但为了真正改善疾病或修复(软骨疾病的类型和状态、细胞的来源和条件、给药方案、组合方法),还需要考虑许多变量。特别是,同种异体 MSCs 是一种有利的细胞产品。用于临床前评估的动物模型的选择也与成功转化为临床实践相关。考虑到该领域的局限性,在成熟的动物模型(包括大型动物)中进行严格的比较和验证研究,对于进一步临床试验的开展仍然是必要的。本综述对小型和大型动物模型中的研究进行了评估,这应该有助于阐明基于 MSC 的疗法在关节软骨修复中的适用性。