Evidence map›Paper›PMID 40516530›Full record

ArticleCell stem cell2025

Rapid generation of functional vascular organoids via simultaneous transcription factor activation of endothelial and mural lineages.

Liyan Gong, Yadong Zhang, Yonglin Zhu, Umji Lee, Allen Chilun Luo, Xiang Li, Xi Wang, Danyang Chen, William T Pu, Ruei-Zeng Lin and 5 more

Abstract read
In one paragraph

Article in Cell stem cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed.

  1. Article
  2. Article
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  8. Review
  9. Advances in vascularized organoids.Chinese medical journal · 2026
    Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. [Research advances on the application of skin appendage organoids in wound repair].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2026
    Review
  15. Review
  16. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Liyan GongDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
Yadong ZhangDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Yonglin ZhuDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
Umji LeeDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
Allen Chilun LuoDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA.
Xiang LiDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
Xi WangDepartment of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA.
Danyang ChenDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA.
William T PuDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Ruei-Zeng LinDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
Minglin MaDepartment of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA.
Miao CuiDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA.
Kaifu ChenDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Kai WangDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Beijing Advanced Center of Cellular Homeostasis and Aging-Related Diseases, Peking University, Beijing 100191, China. Electronic address: kai.wang88@pku.edu.cn.
Juan M Melero-MartinDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: juan.meleromartin@childrens.harvard.edu.

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
Vascular networks genetically engineered for protein drug deliveryR01HL128452 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI MELERO-MARTIN, JUAN M, WANG, BO · 2015 to 2024
$4.8M
Regulation of endothelial cell specificationR01HL151450 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI MELERO-MARTIN, JUAN M, PU, WILLIAM TSWENCHING · 2021 to 2024
$2.5M
Human endothelial cell regulation of ossificationR01AR080086 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI Juan M Melero-Martin · 2022 to 2026
$2.1M
A Novel Transcription Factor-Driven Approach for Mural Progenitor Cells GenerationR01HL172968 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI Juan M Melero-Martin · 2024 to 2026
$1.9M
NHLBI NIH HHS R01 HL128452NHLBI NIH HHS R01 HL151450NHLBI NIH HHS R01 HL172968NIAMS NIH HHS R01 AR080086NIDDK NIH HHS P30 DK034854
6 · The paper itself

Abstract

Vascular organoids (VOs) are valuable tools for studying vascular development, disease, and regenerative medicine. However, controlling endothelial and mural compartments independently remains challenging. Here, we present a streamlined method to generate VOs from induced pluripotent stem cells (iPSCs) via orthogonal activation of the transcription factors (TFs) ETV2 and NKX3.1 using Dox-inducible or modRNA systems. This approach enables efficient co-differentiation of endothelial cells (iECs) and mural cells (iMCs), producing functional 3D VOs in 5 days without ECM embedding. VOs matured further upon ECM exposure, forming larger, structured vessels. Single-cell RNA sequencing revealed vascular heterogeneity, and temporal regulation of TF expression allowed modulation of arterial and angiogenic iEC phenotypes. In vivo, VOs engrafted into immunodeficient mice, formed perfused vasculature, and promoted revascularization in models of hind limb ischemia and pancreatic islet transplantation. These findings establish a rapid and versatile VO platform with broad potential for vascular modeling, disease studies, and regenerative cell therapy.

Indexed as

Cell LineageEndothelial CellsOrganoidsTranscription FactorsAnimalsCell DifferentiationHumansInduced Pluripotent Stem CellsMiceNeovascularization, PhysiologicTranscription Factorsblood vessels organoidsendothelial cellsiPSCsischemia modelsmural cellspluripotent stem cellstherapeutic vascularizationtranscription factor inductionvascular differentiationvascular organoids

Identifiers

PMID40516530
PMCPMC12980400

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.