Intranasal Delivery of Mesenchymal Stem Cell Derived Exosomes Loaded with Phosphatase and Tensin Homolog siRNA Repairs Complete Spinal Cord Injury
Intranasal Delivery of Mesenchymal Stem Cell Derived Exosomes Loaded with Phosphatase and Tensin Homolog siRNA Repairs Complete Spinal Cord Injury
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DOI：
10.1021/acsnano.9b01892
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发表时间：
2019-09-01
期刊：
影响因子：
17.1
通讯作者：
Levenberg, Shulamit
中科院分区：
文献类型：
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作者：
Guo, Shaowei;Perets, Nisim;Levenberg, Shulamit
脊髓损伤（SCI）患者通常会出现永久性的神经功能缺损，自发恢复和治疗效果有限。本研究表明，经鼻给药后，来自间充质干细胞（MSC-Exo）的外泌体可以通过血脑屏障并迁移到损伤的脊髓区域。此外，载磷酸酶和紧张素同源小干扰RNA （ExoPTEN）的MSC-Exo可以在鼻内给药后减弱损伤脊髓区域PTEN的表达。此外，加载的MSC-Exo显著促进轴突生长和新生血管形成，同时减少小胶质细胞和星形胶质细胞形成。鼻内ExoPTEN治疗也可以部分改善结构和电生理功能，最重要的是，显著促进完全性脊髓损伤大鼠的功能恢复。结果表明，鼻用ExoPTEN可能在临床上用于促进脊髓损伤患者的康复。
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.