Abstract |
Diabetic peripheral neuropathy ( DPN) is one of the most prevalent chronic complications of diabetes mellitus with no effective treatment. We recently demonstrated that mesenchymal stromal cell (MSC)-derived exosomes (exo-naïve) alleviate neurovascular dysfunction and improve functional recovery. MicroRNA ( miRNA), one of the exosomal cargos, downregulates inflammation-related genes, resulting in suppression of pro-inflammatory gene activation. In the present study, we developed engineered MSC-exosomes loaded with miR-146a (exo-146a) and compared the therapeutic effects of exo-146a with exo-naïve in diabetic (db/db) mice with DPN. Exo-146a possesses a high loading capacity, robust ability to accumulate in peripheral nerve tissues upon systemic administration, and evokes substantially enhanced therapeutic efficacy on neurological recovery compared with exo-naïve. Treatment of DPN in diabetic mice with exo-146a for two weeks significantly increased and decreased nerve conduction velocity, and thermal and mechanical stimuli threshold, respectively, whereas it took four weeks of exo-naive treatment to achieve these improvements. Compared with exo-naïve, exo-146a significantly suppressed the peripheral blood inflammatory monocytes and the activation of endothelial cells via inhibiting Toll-like receptor (TLR)-4/NF-κB signaling pathway. These data provide a proof-of-concept about both the feasibility and efficacy of the exosome-based gene therapy for DPN. The translation of this approach to the clinic has the potential to improve the prospects for people who suffer from DPN.
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Authors | Baoyan Fan, Michael Chopp, Zheng Gang Zhang, Xian Shuang Liu |
Journal | Experimental neurology
(Exp Neurol)
Vol. 341
Pg. 113694
(07 2021)
ISSN: 1090-2430 [Electronic] United States |
PMID | 33727097
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2021. Published by Elsevier Inc. |
Chemical References |
- MicroRNAs
- Mirn146 microRNA, mouse
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Topics |
- Animals
- Diabetes Mellitus, Experimental
(genetics, metabolism, therapy)
- Diabetic Neuropathies
(genetics, metabolism, therapy)
- Exosomes
(genetics, metabolism, transplantation)
- Genetic Therapy
(methods)
- Male
- Mesenchymal Stem Cell Transplantation
(methods)
- Mesenchymal Stem Cells
(metabolism)
- Mice
- Mice, Transgenic
- MicroRNAs
(administration & dosage, genetics, metabolism)
- Tissue Engineering
(methods)
- Treatment Outcome
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