Wang Peng, Zhang Yang, Arntz Onno J, Oliveira Marina C, Yu Taozhao, Yang Zhihua, van der Kraan Peter M, van den Beucken Jeroen J J P, van de Loo Fons A J
Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
Radboud Institute for Medical Innovations, Nijmegen, the Netherlands.
Mater Today Bio. 2025 Jul 18;33:102115. doi: 10.1016/j.mtbio.2025.102115. eCollection 2025 Aug.
Extracellular vesicles (EVs) are heterogeneous in their composition. The proteins on their surface determine their binding properties to the meshwork of extracellular matrix (ECM). Here, we report that type I collagen-binding property separates two subpopulations of EVs from cow milk (mEVs): collagen-binding mEVs ( mEVs) and non-collagen binding mEVs (mEVs). mEVs showed noticeable uptake by human bone marrow mesenchymal stromal cells (hBMSCs) and osteogenic functionality (1.2-fold increase in mineralization). By proteomics profiling we identified Annexin V (AnxV) and confirmed its enrichment on CD9 positive mEVs using immunomagnetic separation. By implanting a hydrogel construct enriched with mEVs into a femoral condyle defect in osteoporotic rats, we demonstrated their superior bone regenerative capacity (2.4-fold increase in bone formation). Our study suggests that EV binding to the ECM protein type I collagen can be used to isolate a functional mEV subpopulation for bone tissue regeneration. This approach represents an important step forward in relating EV properties to their functionality, which will promote clinical translation.
细胞外囊泡（EVs）的组成具有异质性。其表面的蛋白质决定了它们与细胞外基质（ECM）网络的结合特性。在此，我们报告I型胶原结合特性可将牛乳来源的EVs（mEVs）分为两个亚群：胶原结合mEVs（mEVs）和非胶原结合mEVs（mEVs）。mEVs被人骨髓间充质基质细胞（hBMSCs）显著摄取并具有成骨功能（矿化增加1.2倍）。通过蛋白质组学分析，我们鉴定出膜联蛋白V（AnxV），并使用免疫磁珠分离法证实其在CD9阳性mEVs上富集。通过将富含mEVs的水凝胶构建体植入骨质疏松大鼠的股骨髁缺损处，我们证明了它们具有卓越的骨再生能力（骨形成增加2.4倍）。我们的研究表明，EV与ECM蛋白I型胶原的结合可用于分离用于骨组织再生的功能性mEV亚群。这种方法代表了在将EV特性与其功能相关联方面向前迈出的重要一步，这将促进临床转化。
