Tail-vein injection of MSC-derived small extracellular vesicles facilitates the restoration of hippocampal neuronal morphology and function in APP / PS1 mice
Abstract Mesenchymal stem-cell-derived small extracellular vesicles (MSC-EVs), as a therapeutic agent, have shown great promise in the treatment of neurological diseases. To date, the neurorestorative effects and underlying mechanism of MSC-EVs in Alzheimer’s disease (AD) are not well known. Herein,...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-09-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-021-00620-y |
| _version_ | 1818733059558604800 |
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| author | Han Wang Yuqi Liu Junchen Li Tian Wang Yue Hei Huiming Li Xue Wang Lina Wang Ruijing Zhao Weiping Liu Qianfa Long |
| author_facet | Han Wang Yuqi Liu Junchen Li Tian Wang Yue Hei Huiming Li Xue Wang Lina Wang Ruijing Zhao Weiping Liu Qianfa Long |
| author_sort | Han Wang |
| collection | DOAJ |
| description | Abstract Mesenchymal stem-cell-derived small extracellular vesicles (MSC-EVs), as a therapeutic agent, have shown great promise in the treatment of neurological diseases. To date, the neurorestorative effects and underlying mechanism of MSC-EVs in Alzheimer’s disease (AD) are not well known. Herein, we aimed to investigate the action of MSC-EVs on the neuronal deficits in β-amyloid protein (Aβ)-stimulated hippocampal neurons, or AD cell (SHSY5Y cell lines) and animal (APPswe / PS1dE9 mice) models. In the present study, the cell and AD models received a single-dose of MSC-EVs, and were then assessed for behavioral deficits, pathological changes, intracellular calcium transients, neuronal morphology alterations, or electrophysiological variations. Additionally, the nuclear factor E2-related factor 2 (Nrf2, a key mediator of neuronal injury in AD) signaling pathway was probed by western blotting in vitro and in vivo models of AD. Our results showed that MSC-EVs therapy improved the cognitive impairments and reduced the hippocampal Aβ aggregation and neuronal loss in AD mice. Markedly, EV treatment restored the calcium oscillations, dendritic spine alterations, action potential abnormalities, or mitochondrial changes in the hippocampus of AD models. Also, we found that the Nrf2 signaling pathway participated in the actions of MSC-EVs in the cell and animal models. Together, these data indicate that MS-EVs as promising nanotherapeutics for restoration of hippocampal neuronal morphology and function in APP / PS1 mice, further highlighting the clinical values of MSC-EVs in the treatment of AD. |
| first_indexed | 2024-12-17T23:43:27Z |
| format | Article |
| id | doaj.art-9929ba1beac74cb58eefacb94d764eec |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-12-17T23:43:27Z |
| publishDate | 2021-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-9929ba1beac74cb58eefacb94d764eec2022-12-21T21:28:23ZengNature Publishing GroupCell Death Discovery2058-77162021-09-017111010.1038/s41420-021-00620-yTail-vein injection of MSC-derived small extracellular vesicles facilitates the restoration of hippocampal neuronal morphology and function in APP / PS1 miceHan Wang0Yuqi Liu1Junchen Li2Tian Wang3Yue Hei4Huiming Li5Xue Wang6Lina Wang7Ruijing Zhao8Weiping Liu9Qianfa Long10Department of Neurosurgery, Xijing Hospital, Fourth Military Medical UniversityDepartment of Neurosurgery, Xijing Hospital, Fourth Military Medical UniversityDepartment of Neurosurgery, Xijing Hospital, Fourth Military Medical UniversityMini-invasive Neurosurgery and Translational Medical Center, Xi’an Central Hospital, Xi’an Jiaotong UniversityDepartment of Neurosurgery, Xijing Hospital, Fourth Military Medical UniversityDepartment of Neurosurgery, Xijing Hospital, Fourth Military Medical UniversityMini-invasive Neurosurgery and Translational Medical Center, Xi’an Central Hospital, Xi’an Jiaotong UniversityMini-invasive Neurosurgery and Translational Medical Center, Xi’an Central Hospital, Xi’an Jiaotong UniversityMini-invasive Neurosurgery and Translational Medical Center, Xi’an Central Hospital, Xi’an Jiaotong UniversityDepartment of Neurosurgery, Xijing Hospital, Fourth Military Medical UniversityMini-invasive Neurosurgery and Translational Medical Center, Xi’an Central Hospital, Xi’an Jiaotong UniversityAbstract Mesenchymal stem-cell-derived small extracellular vesicles (MSC-EVs), as a therapeutic agent, have shown great promise in the treatment of neurological diseases. To date, the neurorestorative effects and underlying mechanism of MSC-EVs in Alzheimer’s disease (AD) are not well known. Herein, we aimed to investigate the action of MSC-EVs on the neuronal deficits in β-amyloid protein (Aβ)-stimulated hippocampal neurons, or AD cell (SHSY5Y cell lines) and animal (APPswe / PS1dE9 mice) models. In the present study, the cell and AD models received a single-dose of MSC-EVs, and were then assessed for behavioral deficits, pathological changes, intracellular calcium transients, neuronal morphology alterations, or electrophysiological variations. Additionally, the nuclear factor E2-related factor 2 (Nrf2, a key mediator of neuronal injury in AD) signaling pathway was probed by western blotting in vitro and in vivo models of AD. Our results showed that MSC-EVs therapy improved the cognitive impairments and reduced the hippocampal Aβ aggregation and neuronal loss in AD mice. Markedly, EV treatment restored the calcium oscillations, dendritic spine alterations, action potential abnormalities, or mitochondrial changes in the hippocampus of AD models. Also, we found that the Nrf2 signaling pathway participated in the actions of MSC-EVs in the cell and animal models. Together, these data indicate that MS-EVs as promising nanotherapeutics for restoration of hippocampal neuronal morphology and function in APP / PS1 mice, further highlighting the clinical values of MSC-EVs in the treatment of AD.https://doi.org/10.1038/s41420-021-00620-y |
| spellingShingle | Han Wang Yuqi Liu Junchen Li Tian Wang Yue Hei Huiming Li Xue Wang Lina Wang Ruijing Zhao Weiping Liu Qianfa Long Tail-vein injection of MSC-derived small extracellular vesicles facilitates the restoration of hippocampal neuronal morphology and function in APP / PS1 mice Cell Death Discovery |
| title | Tail-vein injection of MSC-derived small extracellular vesicles facilitates the restoration of hippocampal neuronal morphology and function in APP / PS1 mice |
| title_full | Tail-vein injection of MSC-derived small extracellular vesicles facilitates the restoration of hippocampal neuronal morphology and function in APP / PS1 mice |
| title_fullStr | Tail-vein injection of MSC-derived small extracellular vesicles facilitates the restoration of hippocampal neuronal morphology and function in APP / PS1 mice |
| title_full_unstemmed | Tail-vein injection of MSC-derived small extracellular vesicles facilitates the restoration of hippocampal neuronal morphology and function in APP / PS1 mice |
| title_short | Tail-vein injection of MSC-derived small extracellular vesicles facilitates the restoration of hippocampal neuronal morphology and function in APP / PS1 mice |
| title_sort | tail vein injection of msc derived small extracellular vesicles facilitates the restoration of hippocampal neuronal morphology and function in app ps1 mice |
| url | https://doi.org/10.1038/s41420-021-00620-y |
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