Encapsulating has-miR-29a into HuMSCs-derived Exosomes by a Nanoengineering Platform to Efficiently Alleviate Aβ1-42 Expression in APPswe-SH-SY5Y Cells

Background Exosomes derived from human umbilical cord mesenchymal stem cells (HuMSCs) have been utilized as a potential therapeutic candidate to alleviate amyloid β-protein (Aβ) expression in APP/PS1 or 5XFAD transgenic mice due to their low immunogenicity and extensive sources. Accumulated evidence also suggests that encysting appropriate cargos into exosomes can more effectively reduce Aβ expression by interfering with the metabolism of β-Amyloid precursor protein (APP). Therefore, exosomes loaded with bioactive substances to reduce Aβ expression have attracted much attention. A new strategy to load therapeutic exogenous cargoes of interest into exosomes in a high-throughput and straightforward fashion is desired. Results In this study, neuroblastoma SH-SY5Y cells were stably transfected with Swedish mutant APP695K, 595N plasmid to construct a cell model of Aβ overexpression. Then extracted Exosomes from HuMSCs and loaded with micro (miR)-29a via a microfluidic exosome nanoengineering platform (ExoNP) to target a post-transcriptional modification of the β-secretase1 (β-site APP cleaving enzyme 1, BACE1) gene to prevent protein expression. Finally, processed exosomes were utilized to treat APPswe-SH-SY5Y cells and decrease the expression of Aβ1−42 and BACE1 and further alleviated apoptosis. Conclusion HuMSCs-derived exosomes loaded with hsa-miR-29a via ExoNP to efficiently deliver to APPswe-SH-SY5Y cells and alleviate Aβ1−42 expression and promote cell survival.