title: On-Chip Clonal Analysis of Glioma-Stem-Cell Motility and Therapy Resistance.
abstract: Enhanced glioma-stem-cell (GSC) motility and therapy resistance are considered to play key roles in tumor cell dissemination and recurrence. As such, a better understanding of the mechanisms by which these cells disseminate and withstand therapy could lead to more efficacious treatments. Here, we introduce a novel micro-/nanotechnology-enabled chip platform for performing live-cell interrogation of patient-derived GSCs with single-clone resolution. On-chip analysis revealed marked intertumoral differences (>10-fold) in single-clone motility profiles between two populations of GSCs, which correlated well with results from tumor-xenograft experiments and gene-expression analyses. Further chip-based examination of the more-aggressive GSC population revealed pronounced interclonal variations in motility capabilities (up to ∼4-fold) as well as gene-expression profiles at the single-cell level. Chip-supported therapy resistance studies with a chemotherapeutic agent (i.e., temozolomide) and an oligo RNA (anti-miR363) revealed a subpopulation of CD44-high GSCs with strong antiapoptotic behavior as well as enhanced motility capabilities. The living-cell-interrogation chip platform described herein enables thorough and large-scale live monitoring of heterogeneous cancer-cell populations with single-cell resolution, which is not achievable by any other existing technology and thus has the potential to provide new insights into the cellular and molecular mechanisms modulating glioma-stem-cell dissemination and therapy resistance.
authors.affiliation: Department of Surgery, The Ohio State University , 395 West 12th Avenue, Columbus, Ohio 43210.|Department of Biomedical Engineering, The Ohio State University , 1080 Carmack Road, Columbus, Ohio 43210.|Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University , 151 W. Woodruff Avenue, Columbus, Ohio 43210.|Center for Regenerative Medicine and Cell-Based Therapies, The Ohio State University , 460 West 12th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gallego-Perez
authors.affiliation: Department of Biomedical Engineering, The Ohio State University , 1080 Carmack Road, Columbus, Ohio 43210.|Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University , 151 W. Woodruff Avenue, Columbus, Ohio 43210.
authors.forename: Lingqian
authors.initials: L
authors.lastname: Chang
authors.affiliation: Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University , 151 W. Woodruff Avenue, Columbus, Ohio 43210.|Department of Mechanical Engineering, The Ohio State University , 201 West 19th Avenue, Columbus, Ohio 43210.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Shi
authors.affiliation: Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University , 151 W. Woodruff Avenue, Columbus, Ohio 43210.
authors.forename: Junyu
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, University of Alabama , 1824 6th Avenuce South, Birmingham, Alabama 35294.
authors.forename: Sung-Hak
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University , 151 W. Woodruff Avenue, Columbus, Ohio 43210.|Department of Chemical and Biomolecular Engineering, The Ohio State University , 151 West Woodruff Avenue, Columbus, Ohio 43210.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University , 151 W. Woodruff Avenue, Columbus, Ohio 43210.|Department of Chemical and Biomolecular Engineering, The Ohio State University , 151 West Woodruff Avenue, Columbus, Ohio 43210.
authors.forename: Veysi
authors.initials: V
authors.lastname: Malkoc
authors.affiliation: Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University , 151 W. Woodruff Avenue, Columbus, Ohio 43210.|Department of Chemical and Biomolecular Engineering, The Ohio State University , 151 West Woodruff Avenue, Columbus, Ohio 43210.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, University of Alabama , 1824 6th Avenuce South, Birmingham, Alabama 35294.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Minata
authors.affiliation: Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University , 151 W. Woodruff Avenue, Columbus, Ohio 43210.|Department of Chemical and Biomolecular Engineering, The Ohio State University , 151 West Woodruff Avenue, Columbus, Ohio 43210.
authors.forename: Kwang J
authors.initials: KJ
authors.lastname: Kwak
authors.affiliation: Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University , 151 W. Woodruff Avenue, Columbus, Ohio 43210.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Physics, The Ohio State University , 191 West Woodruff Avenue, Columbus, Ohio 43210.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Lafyatis
authors.affiliation: Department of Electrical and Computer Engineering, The Ohio State University , 2015 Neil Avenue, Columbus, Ohio 43210.
authors.forename: Wu
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Biomedical Engineering, The Ohio State University , 1080 Carmack Road, Columbus, Ohio 43210.|Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University , 151 W. Woodruff Avenue, Columbus, Ohio 43210.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hansford
authors.affiliation: Department of Neurosurgery, University of Alabama , 1824 6th Avenuce South, Birmingham, Alabama 35294.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakano
authors.affiliation: Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University , 151 W. Woodruff Avenue, Columbus, Ohio 43210.|Center for Regenerative Medicine and Cell-Based Therapies, The Ohio State University , 460 West 12th Avenue, Columbus, Ohio 43210, United States.|Department of Chemical and Biomolecular Engineering, The Ohio State University , 151 West Woodruff Avenue, Columbus, Ohio 43210.
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000473:pathology*; D002465:Cell Movement; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000166:cytology*; D014407:Tumor Cells, Cultured
keywords: Living single-cell analysis; anti-microRNA; cancer stem cell; cell motility; glioblastoma; nanochannel electroporation