title: Mussel-Inspired Modification of Nanofibers for REST siRNA Delivery: Understanding the Effects of Gene-Silencing and Substrate Topography on Human Mesenchymal Stem Cell Neuronal Commitment.
abstract: In this study, we promote neuronal differentiation of human mesenchymal stem cells (MSCs) through scaffold-mediated sustained release of siRNA targeting RE-1 silencing transcription factor (REST). Poly (ϵ-caprolactone) nanofibers were surface modified with mussel inspired DOPA-melanin (DM) coating for adsorption of REST siRNA. DM modification increased siRNA-loading efficiency and reduced the initial burst release. Fiber alignment and DM modification enhanced REST knockdown efficiencies. Under non-specific differentiation condition, REST silencing and fiber topography enhanced MSC neuronal markers expressions and reduced glial cell commitment. Such scaffolds may find useful applications in enhancing MSCs neuronal differentiation under non-specific conditions such as an in vivo environment.
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459.
authors.forename: Wei Ching
authors.initials: WC
authors.lastname: Low
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459.
authors.forename: Pim-On
authors.initials: PO
authors.lastname: Rujitanaroj
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Dong-Keun
authors.initials: DK
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Jinghao
authors.initials: J
authors.lastname: Kuang
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Messersmith
authors.affiliation: Department of Reproductive Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899.
authors.forename: Jerry Kok Yen
authors.initials: JK
authors.lastname: Chan
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459. SYChew@ntu.edu.sg.|Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232. SYChew@ntu.edu.sg.
authors.forename: Sing Yian
authors.initials: SY
authors.lastname: Chew
mesh_terms: D000327:Adsorption; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049872:Bivalvia / Q000737:chemistry; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004295:Dihydroxyphenylalanine / Q000737:chemistry; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008543:Melanins / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology*; D011091:Polyesters / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000378:metabolism*; D014162:Transfection / Q000379:methods*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D015415:Biomarkers; D004295:Dihydroxyphenylalanine; D005904:Glial Fibrillary Acidic Protein; D008543:Melanins; D011091:Polyesters; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C016240:polycaprolactone
keywords: RE-1 silencing transcription factor; electrospinning; neural differentiation; neuronal differentiation; sustained release