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

ACS Nano. 2019 Sep 24;13(9):10015-10028. doi: 10.1021/acsnano.9b01892. Epub 2019 Aug 29.


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.

Keywords: PTEN siRNA; complete spinal cord injury; exosome; functional recovery; intranasal; targeted delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Axons / pathology
  • Blood-Brain Barrier / pathology
  • Chemotaxis
  • Electrophysiological Phenomena
  • Exosomes / transplantation*
  • Exosomes / ultrastructure
  • Female
  • Ganglia, Spinal / pathology
  • Gold / chemistry
  • Humans
  • Magnetic Resonance Imaging
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / metabolism*
  • Motor Activity
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Neurons / pathology
  • PTEN Phosphohydrolase / metabolism*
  • RNA, Small Interfering / metabolism*
  • Rats, Sprague-Dawley
  • Recovery of Function*
  • Spinal Cord / pathology
  • Spinal Cord Injuries / physiopathology*
  • Spinal Cord Injuries / therapy*


  • RNA, Small Interfering
  • Gold
  • PTEN Phosphohydrolase