Harnessing extracellular vesicles to direct endochondral repair of large bone defects.
Harnessing extracellular vesicles to direct endochondral repair of large bone defects.
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DOI：
10.1302/2046-3758.74.bjr-2018-0006
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发表时间：
2018-04
影响因子：
4.6
通讯作者：
Porter RM
中科院分区：
文献类型：
--
作者：
Ferreira E;Porter RM
大面积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直接修复缺损的治疗策略，包括软骨中间体。虽然培养扩增的干/祖细胞正在为此目的进行评估，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，可以采用由培养扩增的细胞分泌的细胞外囊泡（EV）来克服软骨内修复的关键瓶颈，例如缺损血管化、软骨形成和骨重塑。虽然间充质基质/干细胞是治疗性EV的有希望的来源，但也应该考虑其他供体细胞。基于EV的治疗剂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EV研究中获得的知识有一天可以为合成的工程纳米囊泡的长期开发提供信息。与此同时，从体外细胞培养中获得的电动汽车近期有望用于骨再生医学。该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可能的治疗靶点，用于通过软骨内途径指导修复，并讨论了目前临床转化的障碍。引用这篇文章：E。费雷拉河M.波特利用细胞外囊泡指导大面积骨缺损的软骨内修复。骨关节研究2018;7：263-273。DOI：10.1302/2046-3758.74.BJR-2018-0006。
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.