Intranasal Delivery of Mesenchymal Stem Cell Derived Exosomes Loaded with Phosphatase and Tensin Homolog siRNA Repairs Complete Spinal Cord Injury
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.
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MSC-Exo loaded with PTEN siRNA (ExoPTEN) specifically target and reduce PTEN expression in the SCI area, promoting axonal growth and neovascularization, while mitigating microgliosis and astrogliosis.
“When these MSC-Exos are loaded with phosphatase and tensin homolog (PTEN) small interfering RNA (ExoPTEN), they specifically target and reduce PTEN expression in the SCI area. This targeted intervention not only suppresses PTEN expression but also significantly promotes axonal growth and neovascularization, while concurrently mitigating microgliosis and astrogliosis.”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [297]
In rat models of total spinal cord injury, intranasal ExoPTEN treatment restored structural and electrophysiological capabilities and facilitated substantial functional recovery.
“In rat models of total spinal cord injury, the use of intranasal ExoPTEN treatment has shown a remarkable ability to restore structural and electrophysiological capabilities, and more importantly, it has been shown to facilitate substantial functional recovery.”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [297]
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- Authors
- Guo, S., Perets, N., Betzer, O., Ben-Shaul, S., Sheinin, A., Michaelevski, I., Popovtzer, R., Offen, D., & Levenberg, S.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Tel Aviv University (IL)
- Bar-Ilan University (IL)
- Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel
- Ariel University (IL)
- Corresponding author
- Levenberg, Shulamit
- ORCID
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-08-27
- Volume
- 13
- Issue
- 9
- Pages
- 10015-10028
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W2970026792
- Cited by
- 424
- References
- 4
- Citations by year
- 2026: 34 · 2025: 61 · 2024: 82 · 2023: 63 · 2022: 77 · 2021: 70 · 2020: 33 · 2019: 4
- FWCI
- 33.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation (749/14)
- Ministry of Science, Technology and Space
- Israel Foundation for Spinal Cord Injury
- J&J Shervington Fund
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- spinal cord injury, mesenchymal stem cell-derived exosomes, intranasal drug delivery, PTEN, siRNA delivery, blood-brain barrier, axon growth, neovascularization, microglial activation, astrocyte activation, functional recovery, nerve regeneration
- MeSH terms
- Administration, Intranasal, Animals, Axons, Blood-Brain Barrier, Chemotaxis, Female, Ganglia, Spinal, Gold, Humans, Magnetic Resonance Imaging, Motor Activity, Neurons, Spinal Cord, Spinal Cord Injuries, Rats, Sprague-Dawley, Recovery of Function, RNA, Small Interfering, Mesenchymal Stem Cell Transplantation, PTEN Phosphohydrolase, Nanoparticles, Exosomes, Electrophysiological Phenomena, Mesenchymal Stem Cells
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