Nanofiber-mediated microRNA delivery to enhance differentiation and maturation of oligodendroglial precursor cells.

Autor: Diao HJ; School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore., Low WC; School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore., Milbreta U; School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore., Lu QR; Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Chew SY; School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore. Electronic address: sychew@ntu.edu.sg.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2015 Jun 28; Vol. 208, pp. 85-92. Date of Electronic Publication: 2015 Mar 05.
DOI: 10.1016/j.jconrel.2015.03.005
Abstrakt: Remyelination in the central nervous system (CNS) is critical in the treatment of many neural pathological conditions. Unfortunately, the ability to direct and enhance oligodendrocyte (OL) differentiation and maturation remains limited. It is known that microenvironmental signals, such as substrate topography and biochemical signaling, regulate cell fate commitment. Therefore, in this study, we developed a nanofiber-mediated microRNA (miR) delivery method to control oligodendroglial precursor cell (OPC) differentiation through a combination of fiber topography and gene silencing. Using poly(ε-caprolactone) nanofibers, efficient knockdown of OL differentiation inhibitory regulators were achieved by either nanofiber alone (20-40%, p<0.05) or the synergistic integration with miR-219 and miR-338 (up to 60%, p<0.05). As compared to two-dimensional culture, nanofiber topography enhanced OPC differentiation by inducing 2-fold increase in RIP(+) cells (p<0.01) while the presence of miRs further enhanced the result to 3-fold (p<0.001). In addition, nanofiber-mediated delivery of miR-219 and miR-338 promoted OL maturation by increasing the number of MBP(+) cells significantly (p<0.01). Taken together, the results demonstrate the efficacy of nanofibers in providing topographical cues and microRNA reverse transfection to direct OPC differentiation. Such scaffolds may find useful applications in directing oligodendrocyte differentiation and myelination for treatment of CNS pathological conditions that require remyelination.
(Copyright © 2015 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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