Abstract
Neural stem cells 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 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. Engrafted cerebral organoids harbored a large neural stem cell pool and displayed multilineage neurodifferentiation at two and four week post-grafting. Cerebral organoids therefore represent a promising alternative source to neural stem cells 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.
Significance Statement Neural stem cells hold great promise for neural repair, but conventional cell-based transplant methods face the hurdles of poor graft survival and inadequate neural differentiation. Here, we transplanted cerebral organoids derived from human pluripotent cells into lesioned mouse cortex. We report enhanced survival, robust vascularization, and multilineage differentiation of engrafted human cerebral organoids in host mouse brain. Cerebral organoid transplantation therefore represents an alternative, tissue-based transplantation strategy for neural repair and for modeling human neurodevelopment and CNS diseases in the context of vascularized cortical tissue.
Footnotes
The authors declare no competing financial interests.
This work was supported by the grants from the National Institutes of Health (R01 NS073596) and Friedman Brain Institute at Icahn School of Medicine at Mount Sinai to H.Z.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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