Author:
Liu Zhixiao,Liu Yingying,Li Yu,Xu Sha,Wang Yang,Zhu Yuruchen,Jiang Chu,Wang Kaizhe,Zhang Yinan,Wang Yue
Abstract
AbstractMesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have garnered extensive attention as natural product-based nanomedicines and potential drug delivery vehicles. However, the specific mechanism for regulating MSC-EVs secretion and delivery remains unclear. Here, we demonstrate that extracellular matrix (ECM) stiffness regulates the secretion and delivery of EVs by affecting MSCs' cargo sorting mechanically. Using multi-omics analysis, we found that a decrease in ECM stiffness impeded the sorting of vesicular transport-related proteins and autophagy-related lipids into MSC-EVs, impairing their secretion and subsequent uptake by macrophages. Hence, MSC-EVs with different secretion and uptake behaviors can be produced by changing the stiffness of culture substrates. This study provides new insights into MSC-EV biology and establishes a connection between MSC-EV behaviors and ECM from a biophysical perspective, providing a basis for the rational design of biomedical materials.
Graphical Abstract
Funder
National Natural Science Foundation of China
National Key Research and Development Program Stem Cell and Translational Research Key Proiects
Shanghai Key Laboratory of Cell Engineering
Key Basic Research Project of Foundation Strengthening Program
Publisher
Springer Science and Business Media LLC
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