Oct 2013 - Cerebral organoids model human brain development and microcephaly

Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA. Nature 2013. 19;501:373-9

This excellent work describes the powerful capabilities of 3D cell culture to study human brain development and relating disorders in vitro. The authors relied on the self-organization capacity of pluripotent stem cells to form complex tissues by providing the proper environment necessary for the generation of intrinsic signals and cues which orchestrate brain development. This was achieved by culturing neuroectodermal cells obtained from embryoid bodies in Matrigel droplets which after transfer to a spinning bioreactor formed cerebral organoids with defined brain regions. Organoid differentiation was demonstrated by increasing expression and regionalization of neuronal markers at the expense of stem cell markers, which indicated the development of a variety of brain regions organized into discrete but interdependent domains. This in vitro model bears the great potential to study neurodevelopmental disorders in vitro as the authors were able to recapitulate hypoplasia of cerebral organoids derived from induced pluripotent stem cells of a patient suffering from microcephaly. This is even more striking as mouse models failed to demonstrate the same defect due to species specific differences in brain development. This pioneering work is an important contribution to improve in vitro models for the study of brain development and neurological diseases and for the assessment of developmental and neurological toxicity in the field of drug discovery

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