ETV2 Mediated Differentiation of Human Pluripotent Stem Cells Results in Functional Endothelial Cells for Engineering Advanced Vascularized Microphysiological Models.
Overview
- State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology Chinese Academy of Sciences Beijing China
- Beijing Institute for Stem Cell and Regenerative Medicine Beijing China
- Department of Biological Engineering Massachusetts Institute of Technology Cambridge Massachusetts USA
- Department of Biomedical Engineering Michigan Technological University Houghton Michigan USA
- Health Research Institute Michigan Technological University Houghton Michigan USA
- Bioengineering Department Northeastern University Boston Massachusetts USA
- Synthetic Biology Center Massachusetts Institute of Technology Cambridge Massachusetts USA
- Department of Mechanical Engineering Massachusetts Institute of Technology Cambridge Massachusetts USA
- Ragon Institute of Mass General Brigham MIT and Harvard Cambridge Massachusetts USA
Abstract
Patient‐specific microphysiological models have become a valuable tool for broad applications, revolutionizing biomedical research. However, limitations persist, with functional vasculature being a significant challenge. With the discovery of ETV2's determinant role in specifying EC lineages during differentiation, researchers have adopted techniques involving ETV2 overexpression to produce h‐iECs more efficiently and consistently. Here, we generated multiple h‐iPSC lines with inducible ETV2 expression, and subsequently differentiated them into h‐iECs, which were validated functionally and by key endothelial markers and RNA‐seq analysis. These cells are capable of reproducibly self‐organizing into stable microvascular networks (MVNs) in a microfluidic chip, forming lumenized and functional vessels that mimic the in vivo capillary bed in both morphology and function—a result not achieved using h‐iECs differentiated with previous two‐step methods using the same h‐iPSC lines. Complex microphysiological models featuring perfusable vasculature were also successfully developed using ETV2‐activated h‐iECs, demonstrated with vascularized tumor and blood‐brain barrier (BBB) models. Additionally, by pooling genetically engineered h‐iPSCs with inducible ETV2, we employed an orthogonally induced differentiation approach to enhance vascularization of an organoid model. Our methodology opens avenues in precision medicine, leading to personalized microphysiological models with perfusable vasculature for various applications.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Data links
- ncbi.nlm.nih.gov/
bioproject/ , NCBI; found in “Data Availability Statement”1176017
Data Availability Statement
The data that support the findings of this study are openly available in Gene Expression Omnibus at http://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 13 authors, 5 keywords, 9 MeSH terms, 5 funders, 67 references, 2 RRIDs.
Cite
This paper
Zhang, S., Wan, Z., Wang, L., Wu, C., Zhang, J., Spitz, S., Wang, X., Floryan, M. A., Coughlin, M. F., Pramotton, F. M., Xu, L., Weiss, R., & Kamm, R. D. (2026). ETV2 Mediated Differentiation of Human Pluripotent Stem Cells Results in Functional Endothelial Cells for Engineering Advanced Vascularized Microphysiological Models. Advanced healthcare materials, 15(19), e04849. https://
BibTeX
@article{zhang2026etv2,
author = {Zhang, Shun and Wan, Zhengpeng and Wang, Lei and Wu, Caihong and Zhang, Junkai and Spitz, Sarah and Wang, Xun and Floryan, Marie A. and Coughlin, Mark F. and Pramotton, Francesca M. and Xu, Liling and Weiss, Ron and Kamm, Roger D.},
title = {{ETV2 Mediated Differentiation of Human Pluripotent Stem Cells Results in Functional Endothelial Cells for Engineering Advanced Vascularized Microphysiological Models}},
journal = {Advanced healthcare materials},
year = {2026},
month = mar,
volume = {15},
number = {19},
pages = {e04849},
publisher = {Wiley},
issn = {2192-2640},
doi = {10.1002/
url = {https://
pmid = {41814973},
pmcid = {PMC13206403}
}
RIS
TY - JOUR
AU - Zhang, Shun
AU - Wan, Zhengpeng
AU - Wang, Lei
AU - Wu, Caihong
AU - Zhang, Junkai
AU - Spitz, Sarah
AU - Wang, Xun
AU - Floryan, Marie A.
AU - Coughlin, Mark F.
AU - Pramotton, Francesca M.
AU - Xu, Liling
AU - Weiss, Ron
AU - Kamm, Roger D.
TI - ETV2 Mediated Differentiation of Human Pluripotent Stem Cells Results in Functional Endothelial Cells for Engineering Advanced Vascularized Microphysiological Models
T2 - Advanced healthcare materials
J2 - Adv Healthc Mater
PY - 2026
DA - 2026/
VL - 15
IS - 19
SP - e04849
SN - 2192-2640
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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