Netrin-1–engineered endothelial cell exosomes induce the formation of pre-regenerative niche to accelerate peripheral nerve repair

• DOI: 10.1126/sciadv.adm8454
• Publication Date: 2024-06-28T17:59:32Z
• Authors: Jinsheng Huang; Jiangnan Li; Senrui Li; Xiaoqi Yang; Nianci Huo; Qiang Chen; Wengang Wang; Ningning Yang; Yuanyi Wang; Nan Zhou
• Keywords: Netrin

The formation of vascular niche is pivotal during the early stage peripheral nerve regeneration. Nevertheless, mechanisms in regulation repair remain unclear. Netrin-1 (NTN1) was found up-regulated stump after injury (PNI). Herein, we demonstrated that NTN1-high endothelial cells (NTN1+ECs) were critical component niche, fostering angiogenesis, axon regeneration, and repair-related phenotypes. We also NTN1+EC–derived exosomes (NTN1 EC-EXO) involved as a role. Multi-omics analysis further verified NTN1 EC-EXO carried low-level expression let7a-5p activated key pathways associated with including focal adhesion, guidance, phosphatidylinositol 3-kinase–AKT, mammalian target rapamycin signaling pathway. Together, our study suggested construction pre-regenerative induced by could establish beneficial microenvironment for facilitate functional recovery PNI.