Netrin-1-engineered endothelial cell exosomes induce the formation of pre-regenerative niche to accelerate peripheral nerve repair.
1. Sci Adv. 2024 Jun 28;10(26):eadm8454. doi: 10.1126/sciadv.adm8454. Epub 2024 Jun 28. Netrin-1-engineered endothelial cell exosomes induce the formation of pre-regenerative niche to accelerate peripheral nerve repair. Huang J(1), Li J(1), Li S(1), Yang X(1), Huo N(1), Chen Q(1), Wang W(1), Yang N(2), Wang Y(3), Zhou N(1). Author information: (1)Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China. (2)Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China. (3)Department of Spinal Surgery, The First Hospital of Jilin University, Orthopedics Center, Jilin University, Changchun 130021, China. The formation of vascular niche is pivotal during the early stage of peripheral nerve regeneration. Nevertheless, the mechanisms of vascular niche in the regulation of peripheral nerve repair remain unclear. Netrin-1 (NTN1) was found up-regulated in nerve stump after peripheral nerve injury (PNI). Herein, we demonstrated that NTN1-high endothelial cells (NTN1+ECs) were the critical component of vascular niche, fostering angiogenesis, axon regeneration, and repair-related phenotypes. We also found that NTN1+EC-derived exosomes (NTN1 EC-EXO) were involved in the formation of vascular niche as a critical role. Multi-omics analysis further verified that NTN1 EC-EXO carried a low-level expression of let7a-5p and activated key pathways associated with niche formation including focal adhesion, axon guidance, phosphatidylinositol 3-kinase-AKT, and mammalian target of rapamycin signaling pathway. Together, our study suggested that the construction of a pre-regenerative niche induced by NTN1 EC-EXO could establish a beneficial microenvironment for nerve repair and facilitate functional recovery after PNI. DOI: 10.1126/sciadv.adm8454 PMCID: PMC11212737 PMID: 38941462 [Indexed for MEDLINE]
