The ability of bone for regeneration has long been recognized. However, once beyond a critical size, spontaneous regeneration of bone is limited. Several studies have focused on enhancing bone regeneration by applying mesenchymal stromal/stem cells (MSCs) in the treatment strategies. Despite the therapeutic efficacy of MSCs in bone regeneration, cell-based therapies are impeded by several challenges in maintaining the optimal cell potency and viability during expansion, storage, and final delivery to patients. Recently, there has been a paradigm shift in therapeutic mechanism of MSCs in tissue repair from one based on cellular differentiation and replacement to one based on secretion and paracrine signaling. Among the broad spectrum of trophic factors, extracellular vesicles ​particularly the exosomes have been reported to be therapeutically efficacious in several injury/disease indications, including bone defects and diseases. The current systematic review aims to summarize the results of the existing animal studies which were conducted to evaluate the therapeutic efficacy of MSC exosomes for bone regeneration. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis ​guidelines, the PubMed and The Cochrane Library database were searched for relevant controlled preclinical animal studies. A total of 23 studies were identified, with the total sample size being 690 rats or mice and 38 rabbits. Generally, MSC exosomes were found to be efficacious for bone regeneration in animal models of bone defects and diseases such as osteonecrosis and osteoporosis. In these studies, MSC exosomes promoted new bone formation with supporting vasculature ​and displayed improved morphological, biomechanical, and histological outcomes, coupled with positive effects on cell survival, proliferation, and migration, osteogenesis, and angiogenesis. Unclear-to-low risk in bias and incomplete reporting in the primary studies highlighted the need for standardization in outcome measurements and reporting. Further studies in large animal models to establish the safety and efficacy would provide useful information on guiding the design of clinical trials.

骨骼的再生能力早已得到认可。但是，一旦超过临界大小，骨骼的自发再生就会受到限制。一些研究集中在通过在治疗策略中应用间充质基质/干细胞（MSC）来增强骨骼再生。尽管MSC在骨再生中具有治疗功效，但在扩展，储存和最终交付给患者期间维持最佳细胞效价和生存能力方面的一些挑战阻碍了基于细胞的疗法。最近，在组织修复中，MSCs的治疗机制发生了范式转变，从基于细胞分化和置换的一种转变为基于分泌和旁分泌信号传导的一种。在各种各样的营养因素中，细胞外囊泡尤其是外泌体据报道在多种损伤/疾病适应症（包括骨缺损和疾病）中具有治疗效果。当前的系统综述旨在总结现有动物研究的结果，这些研究旨在评估MSC外泌体对骨骼再生的治疗功效。按照系统评价和荟萃分析的首选报告项目，在PubMed和Cochrane图书馆数据库中搜索相关的受控临床前动物研究。总共鉴定了23项研究，总样本量为690只大鼠或小鼠和38只兔子。通常，在骨缺损和疾病例如骨坏死和骨质疏松症的动物模型中，发现MSC外泌体对骨再生有效。在这些研究中，MSC外泌体通过支持脉管系统促进了新的骨形成，并表现出改善的形态，生物力学和组织学结果，并对细胞存活，增殖和迁移，成骨和血管生成具有积极作用。在主要研究中偏倚风险尚不明确或偏低以及报告不完整，凸显了对结果测量和报告进行标准化的必要性。在大型动物模型中进一步研究以确定其安全性和有效性将为指导临床试验设计提供有用的信息。在主要研究中偏倚风险尚不明确或偏低以及报告不完整，凸显了对结果测量和报告进行标准化的必要性。在大型动物模型中进一步研究以确定其安全性和有效性将为指导临床试验设计提供有用的信息。在主要研究中偏倚风险尚不明确或偏低以及报告不完整，凸显了对结果测量和报告进行标准化的必要性。在大型动物模型中进一步研究以确定其安全性和有效性将为指导临床试验设计提供有用的信息。