Engineering of human brain organoids with a functional vascular-like system. Cakir, B., Xiang, Y., Tanaka, Y., Kural, M. H., Parent, M., Kang, Y., Chapeton, K., Patterson, B., Yuan, Y., He, C., Raredon, M. S. B., Dengelegi, J., Kim, K., Sun, P., Zhong, M., Lee, S., Patra, P., Hyder, F., Niklason, L. E., Lee, S., Yoon, Y., & Park, I. Nature Methods, 16(11):1169–1175, November, 2019. Number: 11 Publisher: Nature Publishing Group![Engineering of human brain organoids with a functional vascular-like system [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Human cortical organoids (hCOs), derived from human embryonic stem cells (hESCs), provide a platform to study human brain development and diseases in complex three-dimensional tissue. However, current hCOs lack microvasculature, resulting in limited oxygen and nutrient delivery to the inner-most parts of hCOs. We engineered hESCs to ectopically express human ETS variant 2 (ETV2). ETV2-expressing cells in hCOs contributed to forming a complex vascular-like network in hCOs. Importantly, the presence of vasculature-like structures resulted in enhanced functional maturation of organoids. We found that vascularized hCOs (vhCOs) acquired several blood-brain barrier characteristics, including an increase in the expression of tight junctions, nutrient transporters and trans-endothelial electrical resistance. Finally, ETV2-induced endothelium supported the formation of perfused blood vessels in vivo. These vhCOs form vasculature-like structures that resemble the vasculature in early prenatal brain, and they present a robust model to study brain disease in vitro.
@article{cakir_engineering_2019,
title = {Engineering of human brain organoids with a functional vascular-like system},
volume = {16},
copyright = {2019 The Author(s), under exclusive licence to Springer Nature America, Inc.},
issn = {1548-7105},
url = {https://www.nature.com/articles/s41592-019-0586-5},
doi = {10.1038/s41592-019-0586-5},
abstract = {Human cortical organoids (hCOs), derived from human embryonic stem cells (hESCs), provide a platform to study human brain development and diseases in complex three-dimensional tissue. However, current hCOs lack microvasculature, resulting in limited oxygen and nutrient delivery to the inner-most parts of hCOs. We engineered hESCs to ectopically express human ETS variant 2 (ETV2). ETV2-expressing cells in hCOs contributed to forming a complex vascular-like network in hCOs. Importantly, the presence of vasculature-like structures resulted in enhanced functional maturation of organoids. We found that vascularized hCOs (vhCOs) acquired several blood-brain barrier characteristics, including an increase in the expression of tight junctions, nutrient transporters and trans-endothelial electrical resistance. Finally, ETV2-induced endothelium supported the formation of perfused blood vessels in vivo. These vhCOs form vasculature-like structures that resemble the vasculature in early prenatal brain, and they present a robust model to study brain disease in vitro.},
language = {en},
number = {11},
urldate = {2024-02-20},
journal = {Nature Methods},
author = {Cakir, Bilal and Xiang, Yangfei and Tanaka, Yoshiaki and Kural, Mehmet H. and Parent, Maxime and Kang, Young-Jin and Chapeton, Kayley and Patterson, Benjamin and Yuan, Yifan and He, Chang-Shun and Raredon, Micha Sam B. and Dengelegi, Jake and Kim, Kun-Yong and Sun, Pingnan and Zhong, Mei and Lee, Sangho and Patra, Prabir and Hyder, Fahmeed and Niklason, Laura E. and Lee, Sang-Hun and Yoon, Young-Sup and Park, In-Hyun},
month = nov,
year = {2019},
note = {Number: 11
Publisher: Nature Publishing Group},
keywords = {Angiogenesis, Neurogenesis, Stem cells, Tissue culture},
pages = {1169--1175},
}
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