Vascularization and engraftment of transplanted human cerebral organoids in mouse cortex

Nicolas Daviaud, Roland H. Friedel, Hongyan Zou

Research output: Contribution to journalArticlepeer-review

130 Scopus citations

Abstract

Neural stem cells (NSCs) hold great promise for neural repair in cases of CNS injury and neurodegeneration; however, conventional cell-based transplant methods face the challenges of poor survival and inadequate neuronal differentiation. Here, we report an alternative, tissue-based transplantation strategy whereby cerebral organoids derived from human pluripotent stem cells (PSCs) were grafted into lesioned mouse cortex. Cerebral organoid transplants exhibited enhanced survival and robust vascularization from host brain as compared to transplants of dissociated neural progenitor cells (NPCs). Engrafted cerebral organoids harbored a large NSC pool and displayed multilineage neurodifferentiation at two and four weeks after grafting. Cerebral organoids therefore represent a promising alternative source to NSCs or fetal tissues for transplantation, as they contain a large set of neuroprogenitors and differentiated neurons in a structured organization. Engrafted cerebral organoids may also offer a unique experimental paradigm for modeling human neurodevelopment and CNS diseases in the context of vascularized cortical tissue.

Original languageEnglish
Article numbere0219-18.2018
JournaleNeuro
Volume5
Issue number6
DOIs
StatePublished - 1 Nov 2018

Keywords

  • CNS injury
  • Cerebral organoid
  • Neural stem cell transplant
  • Vascularization of intracerebral graft

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