Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in bone regenerative medicine. This narrative review presents a rationale for using EVs to improve the repair of large bone defects, highlights promising cell sources and likely therapeutic targets for directing repair through an endochondral pathway, and discusses current barriers to clinical translation. Cite this article: E. Ferreira, R. M. Porter. Harnessing extracellular vesicles to direct endochondral repair of large bone defects. Bone Joint Res 2018;7:263-273. DOI: 10.1302/2046-3758.74.BJR-2018-0006.

中文翻译：

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利用细胞外囊泡直接软骨内修复大骨缺损。


大骨缺损仍然是一个巨大的临床挑战。越来越多的证据支持通过软骨内途径（涉及软骨中间体）直接修复缺损的治疗策略。虽然为此目的正在评估培养扩增的干/祖细胞，但这些细胞将与内源性修复细胞竞争缺血性缺陷内有限的氧气和营养物质。或者，可以利用培养扩增细胞分泌的细胞外囊泡（EV）来克服软骨内修复的关键瓶颈，例如缺陷血管化、软骨生成和骨重塑。虽然间充质基质/干细胞是治疗性 EV 的一个有前途的来源，但也应考虑其他供体细胞。基于 EV 的疗法的功效可能取决于用于控制递送至特定靶细胞的伴随支架的设计。最终，从电动汽车研究中获得的知识有一天可以为合成工程纳米囊泡的长期发展提供信息。与此同时，利用体外细胞培养的电动汽车近期有望用于骨再生医学。这篇叙述性综述提出了使用 EV 改善大骨缺损修复的基本原理，强调了有前途的细胞来源和通过软骨内途径指导修复的可能治疗靶标，并讨论了当前临床转化的障碍。引用这篇文章：E. Ferreira，RM Porter。利用细胞外囊泡直接软骨内修复大骨缺损。骨关节研究2018；7：263-273。 DOI：10.1302/2046-3758.74.BJR-2018-0006。