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In this study we dispersed such<jats:styled-content style=\"fixed-case\">hNSC<\/jats:styled-content>in a three\u2010dimensional artificial extracellular matrix (<jats:styled-content style=\"fixed-case\">aECM<\/jats:styled-content>) and compared their differentiation<jats:italic>in\u00a0vitro<\/jats:italic>and following grafting into the sensorimotor cortex (<jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>) of postnatal day (P)14 rat pups lesioned by localised injection of endothelin\u20101 at P12. After 10\u201343\u00a0days of<jats:italic>in\u00a0vitro<\/jats:italic>differentiation, a few cells remained as<jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>6<jats:sup>+<\/jats:sup>neuroprogenitors but many more resembled post\u2010mitotic neurons expressing doublecortin, \u03b2\u2010tubulin and<jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content>2. These cells remained dispersed throughout the<jats:styled-content style=\"fixed-case\">ECM<\/jats:styled-content>, but with extended long processes for over 50\u00a0\u03bcm.<jats:italic>In vivo<\/jats:italic>, by 1\u00a0month post grafting, cells expressing human specific markers instead organised into cerebral organoids: columns of tightly packed<jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>6 co\u2010expressing progenitor cells arranged around small tubular lumen in rosettes, with a looser network of cells with processes around the outside co\u2010expressing markers of immature neurons including doublecortin, and<jats:styled-content style=\"fixed-case\">CTIP<\/jats:styled-content>2 characteristic of corticofugal neurons. Host cells also invaded the graft including microglia, astrocytes and endothelial cells forming blood vessels. By 10\u00a0weeks post\u2010grafting, the organoids had disappeared and the<jats:styled-content style=\"fixed-case\">aECM<\/jats:styled-content>had started to break down with fewer transplanted cells remaining.<jats:italic>In vitro<\/jats:italic>, cerebral organoids form in rotating incubators that force oxygen and nutrients to the centre of the structures. We have shown that cerebral organoids can form<jats:italic>in\u00a0vivo<\/jats:italic>; intrinsic factors may direct their organisation including infiltration by host blood vessels.<\/jats:p>","DOI":"10.1111\/joa.12827","type":"journal-article","created":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T09:21:38Z","timestamp":1525944098000},"page":"155-166","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Human neural stem cells dispersed in artificial ECM form cerebral organoids when grafted<i>in\u00a0vivo<\/i>"],"prefix":"10.1111","volume":"233","author":[{"given":"Reem","family":"Basuodan","sequence":"first","affiliation":[{"name":"Institute of Neuroscience Newcastle University Newcastle upon Tyne UK"},{"name":"Health and Rehabilitation Sciences Princess Noura bint Abdulrhman University Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna 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