Nanofiber-mediated microRNA delivery to enhance differentiation and maturation of oligodendroglial precursor cells.
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.
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
Hua Jia
HJ
Diao
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
Wei Ching
WC
Low
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
Ulla
U
Milbreta
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.
Q Richard
QR
Lu
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.
Sing Yian
SY
Chew
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D055785:Gene Knockdown Techniques / Q000379:methods; D020868:Gene Silencing / Q000187:drug effects; D035683:MicroRNAs / Q000008:administration & dosage* / Q000494:pharmacology*; D009186:Myelin Sheath / Q000187:drug effects; D057139:Nanofibers / Q000737:chemistry*; D058953:Neural Stem Cells / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects*; D051381:Rats; D014162:Transfection
D003692:Delayed-Action Preparations; C000591851:MIRN219 microRNA, rat; C573089:MIRN338 microRNA, rat; D035683:MicroRNAs
Gene silencing; MicroRNA; Nanofiber; Oligodendrocyte precursor cell; Remyelination; Reverse transfection; Sustained release; Topography