Infante Arantza, Alcorta-Sevillano Natividad, Macías Iratxe, Rodríguez Clara I
Stem Cells and Cell Therapy Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, Plaza de Cruces S/N, 48903 Barakaldo, Spain.
Department of Cell Biology and Histology, University of Basque Country (UPV/EHU), 48940 Leioa, Spain.
Int J Mol Sci. 2022 Feb 7;23(3):1865. doi: 10.3390/ijms23031865.
The incidence of bone-related disorders is continuously growing as the aging of the population in developing countries continues to increase. Although therapeutic interventions for bone regeneration exist, their effectiveness is questioned, especially under certain circumstances, such as critical size defects. This gap of curative options has led to the search for new and more effective therapeutic approaches for bone regeneration; among them, the possibility of using extracellular vesicles (EVs) is gaining ground. EVs are secreted, biocompatible, nano-sized vesicles that play a pivotal role as messengers between donor and target cells, mediated by their specific cargo. Evidence shows that bone-relevant cells secrete osteoanabolic EVs, whose functionality can be further improved by several strategies. This, together with the low immunogenicity of EVs and their storage advantages, make them attractive candidates for clinical prospects in bone regeneration. However, before EVs reach clinical translation, a number of concerns should be addressed. Unraveling the EVs' mode of action in bone regeneration is one of them; the molecular mediators driving their osteoanabolic effects in acceptor cells are now beginning to be uncovered. Increasing the functional and bone targeting abilities of EVs are also matters of intense research. Here, we summarize the cell sources offering osteoanabolic EVs, and the current knowledge about the molecular cargos that mediate bone regeneration. Moreover, we discuss strategies under development to improve the osteoanabolic and bone-targeting potential of EVs.
随着发展中国家人口老龄化的持续加剧，与骨相关疾病的发病率也在不断上升。尽管存在用于骨再生的治疗干预措施，但其有效性受到质疑，尤其是在某些情况下，如临界尺寸骨缺损。这种治疗选择的差距促使人们寻找新的、更有效的骨再生治疗方法；其中，使用细胞外囊泡（EVs）的可能性越来越大。EVs是分泌型、生物相容性的纳米级囊泡，通过其特定的货物在供体细胞和靶细胞之间作为信使发挥关键作用。有证据表明，与骨相关的细胞会分泌促骨合成代谢的EVs，其功能可通过多种策略进一步改善。这一点，再加上EVs的低免疫原性及其储存优势，使其成为骨再生临床应用的有吸引力的候选者。然而，在EVs实现临床转化之前，有许多问题需要解决。弄清楚EVs在骨再生中的作用模式就是其中之一；目前正在开始揭示驱动其在受体细胞中产生促骨合成代谢作用的分子介质。提高EVs的功能和骨靶向能力也是深入研究的课题。在这里，我们总结了提供促骨合成代谢EVs的细胞来源，以及目前关于介导骨再生的分子货物的知识。此外，我们还讨论了正在开发的提高EVs促骨合成代谢和骨靶向潜力的策略。
