Intranasal Delivery of Mesenchymal Stem Cell Derived Exosomes Loaded with Phosphatase and Tensin Homolog siRNA Repairs Complete Spinal Cord Injury

Shaowei Guo, Nisim Perets, Oshra Betzer, Shahar Ben-Shaul, Anton Sheinin, Izhak Michaelevski, Rachela Popovtzer, Daniel Offen, Shulamit Levenberg

Research output: Contribution to journalArticlepeer-review

239 Scopus citations

Abstract

Individuals with spinal cord injury (SCI) usually suffer from permanent neurological deficits, while spontaneous recovery and therapeutic efficacy are limited. Here, we demonstrate that when given intranasally, exosomes derived from mesenchymal stem cells (MSC-Exo) could pass the blood brain barrier and migrate to the injured spinal cord area. Furthermore, MSC-Exo loaded with phosphatase and tensin homolog small interfering RNA (ExoPTEN) could attenuate the expression of PTEN in the injured spinal cord region following intranasal administrations. In addition, the loaded MSC-Exo considerably enhanced axonal growth and neovascularization, while reducing microgliosis and astrogliosis. The intranasal ExoPTEN therapy could also partly improve structural and electrophysiological function and, most importantly, significantly elicited functional recovery in rats with complete SCI. The results imply that intranasal ExoPTEN may be used clinically to promote recovery for SCI individuals.

Original languageEnglish
Pages (from-to)10015-10028
Number of pages14
JournalACS Nano
Volume13
Issue number9
DOIs
StatePublished - 24 Sep 2019

Bibliographical note

Publisher Copyright:
© 2019 American Chemical Society.

Keywords

  • PTEN siRNA
  • complete spinal cord injury
  • exosome
  • functional recovery
  • intranasal
  • targeted delivery

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