Azoidis Ioannis, Cox Sophie C, Davies Owen G
School of Chemical Engineering, University of Birmingham, Birmingham, UK.
School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK.
J Tissue Eng. 2018 Nov 2;9:2041731418810130. doi: 10.1177/2041731418810130. eCollection 2018 Jan-Dec.
Extracellular vesicles comprise a heterogenous population of exosomes and microvesicles that have critical roles in intercellular signalling and tissue development. These complex particles have been implicated as mediators of the therapeutic effects of stem cells via the transfer of an assorted cargo of proteins and nucleic acids, which can modulate inflammation and enhance endogenous regeneration in a range of tissues. In addition, extracellular vesicles have the capacity to be loaded with therapeutic molecules for targeted delivery of pharmaceuticals. The versatility, biostability and biocompatibility of extracellular vesicles make them appealing for regenerative medicine and may endow considerable advantages over single molecule approaches. Furthermore, since production can be optimised and assessed ex vivo, extracellular vesicles present a decreased risk of neoplastic transformation when compared with cell-based methods. To date, the contribution of vesicles to tissue development has perhaps been most comprehensively defined within hard tissues, such as endochondral bone, where they were first identified in 1969 and henceforth referred to as matrix vesicles. Within developing bone, vesicles function as vehicles for the delivery of pro-osteogenic factors and initiate early nucleational events necessary for matrix mineralisation. However, advancement in our understanding of the biogenesis and characterisation of matrix vesicles has occurred largely in parallel to associated developments in wider extracellular vesicle biology. As such, there is a requirement to align current understanding of matrix vesicle-mediated mineralisation within the context of an evolving literature surrounding exosomes and microvesicles. In this review, we present an overview of current progress and opinion surrounding the application of vesicles in regenerative medicine with a primary focus on their potential as an acellular approach for enhancing hard tissue regeneration. This is balanced with an assessment of areas where further development is required to maximise their application for regenerative medicine.
细胞外囊泡由外泌体和微囊泡组成，它们在细胞间信号传导和组织发育中发挥着关键作用。这些复杂的颗粒被认为是干细胞治疗作用的介质，通过转移各种蛋白质和核酸货物来调节炎症并增强一系列组织中的内源性再生。此外，细胞外囊泡有能力装载治疗分子用于药物的靶向递送。细胞外囊泡的多功能性、生物稳定性和生物相容性使其在再生医学中颇具吸引力，相较于单分子方法可能具有显著优势。此外，由于可以在体外优化和评估其生产，与基于细胞的方法相比，细胞外囊泡发生肿瘤转化的风险降低。迄今为止，囊泡对组织发育的贡献可能在硬组织（如软骨内骨）中得到了最全面的定义，1969年在硬组织中首次发现了囊泡，此后被称为基质囊泡。在发育中的骨骼中，囊泡作为促骨生成因子递送的载体，并启动基质矿化所需的早期成核事件。然而，我们对基质囊泡生物发生和特征的理解进展在很大程度上与更广泛的细胞外囊泡生物学的相关发展并行。因此，需要在围绕外泌体和微囊泡不断发展的文献背景下，梳理当前对基质囊泡介导矿化的理解。在本综述中，我们概述了囊泡在再生医学中应用的当前进展和观点，主要关注其作为增强硬组织再生的无细胞方法的潜力。同时，对需要进一步发展以最大限度地将其应用于再生医学的领域进行了评估，以达到平衡。
