Microfiber drug/gene delivery platform for study of myelination

Ong, William, Lin, Junquan, Bechler, Marie E., Wang, Kai, Wang, Mingfeng, ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377 and Chew, Sing Yian (2018) Microfiber drug/gene delivery platform for study of myelination. Acta Biomaterialia, 75. pp. 152-160. ISSN 1742-7061

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Abstract

Our ability to rescue functional deficits after demyelinating diseases or spinal cord injuries is limited by our lack of understanding of the complex remyelination process, which is crucial to functional recovery. In this study, we developed an electrospun suspended poly(ε-caprolactone) microfiber platform to enable the screening of therapeutics for remyelination. As a proof of concept, this platform employed scaffold-mediated non-viral delivery of a microRNA (miR) cocktail to promote oligodendrocyte precursor cells (OPCs) differentiation and myelination. We observed enhanced OPCs differentiation when the cells were transfected with miR-219 and miR-338 on the microfiber substrates. Moreover, miRs promoted the formation of MBP+ tubular extensions around the suspended fibers, which was indicative of myelination, instead of flat myelin membranes on 2D substrates. In addition, OPCs that were transfected with the cocktail of miRs formed significantly longer and larger amounts of MBP+ extensions. Taken together, these results demonstrate the efficacy of this functional screening platform for understanding myelination.  * Statement of Significance: The lack of understanding of the complex myelination process has hindered the discovery of effective therapeutic treatments for demyelinating diseases. Hence, in vitro models that enable systematic understanding, visualization and quantification of myelination are valuable. Unfortunately, achieving reproducible in vitro myelination by oligodendrocytes (OLs) remains highly challenging. Here, we engineered a suspended microfiber platform that enables sustained non-viral drug/gene delivery to study OL differentiation and myelination. Sustained drug delivery permits the investigation of OL development, which spans several weeks. We show that promyelinogenic microRNAs promoted OL differentiation and myelination on this platform. Our engineered microfiber substrate could serve as a drug/gene screening platform and facilitate future translation into direct implantable devices for in vivo remyelination purposes.

Item Type: Article
Additional Information: Funding Information: The partial funding support from the Singapore National Research Foundation (under its NMRC-CBRG grant (NMRC/CBRG/0096/2015) and administered by the Singapore Ministry of Health’s National Medical Research Council); and MOE Tier 1 grant (RG148/14) are acknowledged. William Ong would like to thank Nanyang Technological University (NTU) Interdisciplinary Graduate School for its Graduate Scholarship. Funding Information: The partial funding support from the Singapore National Research Foundation (under its NMRC-CBRG grant (NMRC/CBRG/0096/2015) and administered by the Singapore Ministry of Health's National Medical Research Council); and MOE Tier 1 grant (RG148/14) are acknowledged. William Ong would like to thank Nanyang Technological University (NTU) Interdisciplinary Graduate School for its Graduate Scholarship.
Uncontrolled Keywords: electrospinning,microrna,non-viral gene delivery,oligodendrocyte precursor cells,oligodendrocytes,rna interference,biotechnology,biomaterials,biochemistry,biomedical engineering,molecular biology ,/dk/atira/pure/subjectarea/asjc/1300/1305
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 15 Jul 2022 14:31
Last Modified: 21 Jul 2022 10:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/86234
DOI: 10.1016/j.actbio.2018.06.011

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