小泡
间充质干细胞
长寿
细胞生物学
间质细胞
化学
微泡
蛋白质组学
细胞
生物
生物化学
膜
基因
癌症研究
小RNA
遗传学
作者
Jeroen Vos,Hector Tejeda-Mora,Ana Merino,Longlong Wu,Wouter W. Woud,Jeroen Demmers,Wilfred F. J. van IJcken,Marlies E.J. Reinders,Martin J. Hoogduijn
标识
DOI:10.1016/j.jconrel.2022.08.060
摘要
Vesicle-based medicines hold great promise for therapy development but essential knowledge on the bio-distribution and longevity of vesicles after administration is lacking. We generated vesicles from the membranes of human mesenchymal stromal cells (MSC) and we demonstrated earlier that these so-called membrane particles (MP) mediate immunomodulatory and regenerative responses in target cells. In the present study we examined the bio-distribution and longevity of MP after intravenous administration in mice. While most vesicle tracking methods are based on imaging techniques, which require labeling of vesicles and can only detect dense accumulations of vesicles, we used proteomics analysis to detect the presence of MP-derived proteins in multiple organs and tissues. MP proteins were mainly present in plasma and leukocytes at 1 h after injection, indicating that MP - in contrast to whole MSC - do not accumulate in the lungs upon first passage but remain in circulation. After 24 h, MP proteins were still present in plasma but were most abundant in the liver. RNA sequencing of livers demonstrated that MP impact liver function and in particular induce metabolic pathways. These data provide a clear view of the bio-distribution and longevity of MP, which is likely extrapolatable to other types of vesicles, and demonstrate that MP circulate for up to 24 h and may be a tool for targeting the liver.
科研通智能强力驱动
Strongly Powered by AbleSci AI