1. Academic Validation
  2. Peripheral nervous system lymphatic vessels: A simple delivery route to promote nerve regeneration

Peripheral nervous system lymphatic vessels: A simple delivery route to promote nerve regeneration

  • Exp Neurol. 2024 Apr 28:377:114783. doi: 10.1016/j.expneurol.2024.114783.
Senrui Li 1 Jiangnan Li 1 Xiaoqi Yang 2 Jinsheng Huang 1 Shuai Feng 3 Zhenjun Xie 3 Ningning Yang 4 Yuanyi Wang 5 Nan Zhou 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China.
  • 2 Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China; State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 3 Department of Hand and Podiatric Surgery, Henan Provincial People's Hospital, Zhengzhou 450000, China.
  • 4 Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China. Electronic address: yangningningzzu@126.com.
  • 5 Department of Spinal Surgery, The First Hospital of Jilin University, Orthopedics Center, Jilin University, Changchun 130021, China. Electronic address: wangyuanyi@jlu.edu.cn.
  • 6 Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China. Electronic address: fcczhoun@zzu.edu.cn.
Abstract

The structural and functional features of lymphatic vessels in the peripheral nervous system (pLVs) is still unclear. Here, we clarify the existence of pLVs in rats, PROX1-EGFP transgenic mice and human, and exhibit a clear three-dimensional structure for helping understand its structural features. Moreover, two specific phenotypes of lymphatics endothelial cells (Rnd1Hi LECs and CCL21Hi LECs) in peripheral nerves are well characterized by single-cell Sequencing. Subsequently, the ability of trans-lymphatic delivery to peripheral nerves via pLVs has been dynamically demonstrated. After peripheral nerve injury (PNI), extensive lymphangiogenesis occurs in the lesion area and further enhances the efficiency of retrograde lymphatic-nerve transport. In PNI animal models, subcutaneously footpad-injected exosomes are efficiently delivered to sciatic nerve via pLVs which can promote nerve regeneration. The trans-lymphatic delivery to peripheral nerves via pLVs can subtly bypass BNB which provides an easy and alternative delivery route for PNI treatment.

Keywords

Delivery routes; Exosomes; Lymphatic vessels; Nerve regenerations; Peripheral nerves.

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