Cell Reports
Volume 23, Issue 9, 29 May 2018, Pages 2732-2743
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Article
Human Pluripotent Stem-Cell-Derived Cortical Neurons Integrate Functionally into the Lesioned Adult Murine Visual Cortex in an Area-Specific Way

https://doi.org/10.1016/j.celrep.2018.04.094Get rights and content
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Highlights

  • Human PSC-derived cortical neurons efficiently integrate into the adult mouse brain

  • PSC-derived human neurons reestablish axonal pathways in the lesioned adult cortex

  • Restoration of cortical pathways requires a donor and recipient area-identity match

Summary

The transplantation of pluripotent stem-cell-derived neurons constitutes a promising avenue for the treatment of several brain diseases. However, their potential for the repair of the cerebral cortex remains unclear, given its complexity and neuronal diversity. Here, we show that human visual cortical cells differentiated from embryonic stem cells can be transplanted and can integrate successfully into the lesioned mouse adult visual cortex. The transplanted human neurons expressed the appropriate repertoire of markers of six cortical layers, projected axons to specific visual cortical targets, and were synaptically active within the adult brain. Moreover, transplant maturation and integration were much less efficient following transplantation into the lesioned motor cortex, as previously observed for transplanted mouse cortical neurons. These data constitute an important milestone for the potential use of human PSC-derived cortical cells for the reassembly of cortical circuits and emphasize the importance of cortical areal identity for successful transplantation.

Keywords

brain repair
cerebral cortex
pluripotent stem cells
brain transplantation
neural wiring

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Present address: Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL 60611, USA

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