Journal
ACS NANO
Volume 13, Issue 9, Pages 10015-10028Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b01892
Keywords
intranasal; exosome; PTEN siRNA; targeted delivery; functional recovery; complete spinal cord injury
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Funding
- J&J Shervington Fund
- Israel Foundation for Spinal Cord Injury
- Israel Science Foundation ISF [749/14]
- Brainboost project
- Council for Higher Education
- Ministry of Science, Technology Space Israel
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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.
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