Using Extracellular Vesicles Released by GDNF-transfected Macrophages for Therapy of Parkinson’s Disease
Abstract Extracellular vesicles (EVs) are cell-derived nanoparticles that facilitate transport of proteins, lipids and genetic material playing important roles in intracellular communication. They have a remarkable potential as non-toxic and non-immunogenic nanocarriers for drug delivery to unreachable organs and tissues, in particular, the central nervous system (CNS). Herein, we developed a novel platform based on macrophage derived EVs to treat Parkinson’s disease (PD). Specifically, we evaluated the therapeutic potential of EVs secreted by autologous macrophages that were transfectedex vivoto express glial cell line-derived neurotrophic factor (GDNF). EV-GDNF were collected from conditioned media of GDNF-transfected macrophages and characterized for GDNF content, size, charge, and expression of EV-specific proteins. The data revealed that along with the encoded neurotrophic factor, EVs released by pre-transfected macrophages carry GDNF-encoding DNA. Four months-old transgenic Parkin Q311(X)A mice were treated with EV-GDNFviaintranasal administration, and the effect of this therapeutic intervention on locomotor functions was assessed over a year. Significant improvements in mobility, increase in neuronal survival, and decrease in neuroinflammation were found in PD mice treated with EV-GDNF. No offsite toxicity caused by EV-GDNF administrations was detected. Overall, EV-based approach can provide a versatile and potent therapeutic intervention for PD..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 22. Nov. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Yuling [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2022.05.25.493424 |
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| PPN (Katalog-ID): |
XBI036126454 |
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| 520 | |a Abstract Extracellular vesicles (EVs) are cell-derived nanoparticles that facilitate transport of proteins, lipids and genetic material playing important roles in intracellular communication. They have a remarkable potential as non-toxic and non-immunogenic nanocarriers for drug delivery to unreachable organs and tissues, in particular, the central nervous system (CNS). Herein, we developed a novel platform based on macrophage derived EVs to treat Parkinson’s disease (PD). Specifically, we evaluated the therapeutic potential of EVs secreted by autologous macrophages that were transfectedex vivoto express glial cell line-derived neurotrophic factor (GDNF). EV-GDNF were collected from conditioned media of GDNF-transfected macrophages and characterized for GDNF content, size, charge, and expression of EV-specific proteins. The data revealed that along with the encoded neurotrophic factor, EVs released by pre-transfected macrophages carry GDNF-encoding DNA. Four months-old transgenic Parkin Q311(X)A mice were treated with EV-GDNFviaintranasal administration, and the effect of this therapeutic intervention on locomotor functions was assessed over a year. Significant improvements in mobility, increase in neuronal survival, and decrease in neuroinflammation were found in PD mice treated with EV-GDNF. No offsite toxicity caused by EV-GDNF administrations was detected. Overall, EV-based approach can provide a versatile and potent therapeutic intervention for PD. | ||
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| 700 | 1 | |a Fallon, John K. |4 aut | |
| 700 | 1 | |a Rodriguez, Myosotys |4 aut | |
| 700 | 1 | |a Swain, Carson J. |4 aut | |
| 700 | 1 | |a Arzt, Camryn J. |4 aut | |
| 700 | 1 | |a Smith, Philip C. |4 aut | |
| 700 | 1 | |a Loop, Matthew Shane |4 aut | |
| 700 | 1 | |a Harrison, Emily B. |4 aut | |
| 700 | 1 | |a El-Hage, Nazira |4 aut | |
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