PMID- 28562594 OWN - NLM STAT- MEDLINE DCOM- 20170818 LR - 20210224 IS - 1546-1696 (Electronic) IS - 1087-0156 (Print) IS - 1087-0156 (Linking) VI - 35 IP - 7 DP - 2017 Jul TI - Guided self-organization and cortical plate formation in human brain organoids. PG - 659-666 LID - 10.1038/nbt.3906 [doi] AB - Three-dimensional cell culture models have either relied on the self-organizing properties of mammalian cells or used bioengineered constructs to arrange cells in an organ-like configuration. While self-organizing organoids excel at recapitulating early developmental events, bioengineered constructs reproducibly generate desired tissue architectures. Here, we combine these two approaches to reproducibly generate human forebrain tissue while maintaining its self-organizing capacity. We use poly(lactide-co-glycolide) copolymer (PLGA) fiber microfilaments as a floating scaffold to generate elongated embryoid bodies. Microfilament-engineered cerebral organoids (enCORs) display enhanced neuroectoderm formation and improved cortical development. Furthermore, reconstitution of the basement membrane leads to characteristic cortical tissue architecture, including formation of a polarized cortical plate and radial units. Thus, enCORs model the distinctive radial organization of the cerebral cortex and allow for the study of neuronal migration. Our data demonstrate that combining 3D cell culture with bioengineering can increase reproducibility and improve tissue architecture. FAU - Lancaster, Madeline A AU - Lancaster MA AUID- ORCID: 0000-0003-2324-8853 AD - IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna, Austria. AD - MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK. FAU - Corsini, Nina S AU - Corsini NS AD - IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna, Austria. FAU - Wolfinger, Simone AU - Wolfinger S AD - IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna, Austria. FAU - Gustafson, E Hilary AU - Gustafson EH AUID- ORCID: 0000-0003-3978-8088 AD - IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna, Austria. FAU - Phillips, Alex W AU - Phillips AW AD - MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK. FAU - Burkard, Thomas R AU - Burkard TR AD - IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna, Austria. AD - IMP-Institute of Molecular Pathology, Vienna, Austria. FAU - Otani, Tomoki AU - Otani T AD - Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, UK. FAU - Livesey, Frederick J AU - Livesey FJ AD - Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, UK. FAU - Knoblich, Juergen A AU - Knoblich JA AD - IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna, Austria. LA - eng GR - MC_UP_1201/9/MRC_/Medical Research Council/United Kingdom GR - MR/L023784/1/MRC_/Medical Research Council/United Kingdom GR - MR/L023784/2/MRC_/Medical Research Council/United Kingdom PT - Journal Article DEP - 20170531 PL - United States TA - Nat Biotechnol JT - Nature biotechnology JID - 9604648 SB - IM CIN - Cell Stem Cell. 2017 Aug 3;21(2):157-158. PMID: 28777940 EIN - Nat Biotechnol. 2018 Oct 11;36(10):1016. PMID: 30307926 MH - Batch Cell Culture Techniques/*methods MH - Cells, Cultured MH - Guided Tissue Regeneration/methods MH - Humans MH - Neural Stem Cells/cytology/*physiology MH - Neurogenesis/*physiology MH - Organ Culture Techniques/methods MH - Organoids/cytology/*growth & development MH - Prosencephalon/cytology/*growth & development MH - Tissue Engineering/*methods PMC - PMC5824977 MID - EMS76188 COIS- Declaration of competing financial interests M.A.L. and J.A.K. have filed a patent application for use of this technology in future disease modeling and toxicology testing. EDAT- 2017/06/01 06:00 MHDA- 2017/08/19 06:00 PMCR- 2018/02/23 CRDT- 2017/06/01 06:00 PHST- 2017/04/23 00:00 [received] PHST- 2017/05/18 00:00 [accepted] PHST- 2017/06/01 06:00 [pubmed] PHST- 2017/08/19 06:00 [medline] PHST- 2017/06/01 06:00 [entrez] PHST- 2018/02/23 00:00 [pmc-release] AID - nbt.3906 [pii] AID - 10.1038/nbt.3906 [doi] PST - ppublish SO - Nat Biotechnol. 2017 Jul;35(7):659-666. doi: 10.1038/nbt.3906. Epub 2017 May 31.