TY - JOUR
T1 - Exosomes loaded with PTEN siRNA leads to functional recovery after complete transection of the spinal cord by specifically targeting the damaged area,
AU - Offen, D.
AU - Perets, N.
AU - Guo, S.
AU - Betzer, O.
AU - Popovtzer, R.
AU - Ben-Shaul, S.
AU - Sheinin, A.
AU - ., null
PY - 2019
Y1 - 2019
N2 - Background & Aim Complete spinal cord injury (SCI) is a debilitating disease which usually leads to permanent functional impairments, with various complications and limited spontaneous recovery or effective treatment. Here, we report that in rats with complete SCI, intranasal administrations of mesenchymal stem cells-derived exosomes (MSC-Exo) could penetrate the blood-brain barrier, home selectively to the spinal cord lesion, and show affinity to neurons within the lesion. When these exosomes were loaded with phosphatase and tensin homolog small interfering RNA, termed ExoPTEN, they migrated from the nose and silenced PTEN expression in the lesion. Furthermore, the loaded exosomes promoted robust axonal regeneration and angiogenesis, accompanied by decreased astrogliosis and microgliosis. Moreover, the intranasal ExoPTEN treatment partially restored electrophysiological and structural integrity, and most importantly, enabled remarkable functional recovery. This rapid, non-invasive approach, using cell-free nano-swimmers carrying molecules to target pathophysiological mechanisms, suggests a novel strategy for clinical translation to SCI and beyond. Methods, Results & Conclusion MSC-exo were extracted from Human bone marrow mesenchymal stem cells. All rats had complete transection of the spinal cord. MSC-exo were loaded with co-incubation together with siRNA for PTEN conjugated to cholesterol. The MSC-exo were given by intranasal administration 1-4 hours post-SCI.
AB - Background & Aim Complete spinal cord injury (SCI) is a debilitating disease which usually leads to permanent functional impairments, with various complications and limited spontaneous recovery or effective treatment. Here, we report that in rats with complete SCI, intranasal administrations of mesenchymal stem cells-derived exosomes (MSC-Exo) could penetrate the blood-brain barrier, home selectively to the spinal cord lesion, and show affinity to neurons within the lesion. When these exosomes were loaded with phosphatase and tensin homolog small interfering RNA, termed ExoPTEN, they migrated from the nose and silenced PTEN expression in the lesion. Furthermore, the loaded exosomes promoted robust axonal regeneration and angiogenesis, accompanied by decreased astrogliosis and microgliosis. Moreover, the intranasal ExoPTEN treatment partially restored electrophysiological and structural integrity, and most importantly, enabled remarkable functional recovery. This rapid, non-invasive approach, using cell-free nano-swimmers carrying molecules to target pathophysiological mechanisms, suggests a novel strategy for clinical translation to SCI and beyond. Methods, Results & Conclusion MSC-exo were extracted from Human bone marrow mesenchymal stem cells. All rats had complete transection of the spinal cord. MSC-exo were loaded with co-incubation together with siRNA for PTEN conjugated to cholesterol. The MSC-exo were given by intranasal administration 1-4 hours post-SCI.
UR - http://scholar.google.com/scholar?num=3&hl=en&lr=&q=allintitle%3A%20Exosomes%20loaded%20with%20PTEN%20siRNA%20leads%20to%20functional%20recovery%20after%20complete%20transection%20of%20the%20spinal%20cord%20by%20specifically%20targeting%20the%20damaged%20area%2C%20author%3AOffen%20OR%20author%3APerets%20OR%20author%3AGuo%20OR%20author%3ABetzer%20OR%20author%3APopovtzer%20OR%20author%3ABen-Shaul%20OR%20author%3ASheinin%20OR%20author%3A...&as_ylo=2019&as_yhi=&btnG=Search&as_vis=0
UR - https://www.mendeley.com/catalogue/82803367-d82b-300a-aa19-9da81da1b8bc/
U2 - https://doi.org/10.1016/j.jcyt.2019.04.024
DO - https://doi.org/10.1016/j.jcyt.2019.04.024
M3 - مقالة
SN - 1465-3249
VL - 21
SP - e7-e8
JO - Cytotherapy
JF - Cytotherapy
IS - 5
ER -
