ArticleCell2025
Co-development of mesoderm and endoderm enables organotypic vascularization in lung and gut organoids.
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Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50citing papers in PubMed
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Who cites it
50 citing papers in PubMed.
- Overcoming diffusion limits to advance brain organoids.Neural regeneration research · 2026Article
- A xeno-free human iPSC-derived prostate organoid platform for multilineage differentiation and genetic manipulation.Cell reports methods · 2026Article
- Gut-on-Chip Models for Host-Microbiome Studies: A Systematic Review.Microorganisms · 2026Review
- Endodermal Organoids Along Two Axes: Single-Organ Fidelity, Inter-Organ Reconstruction, and the Unbuilt Gut-Lung Frontier.Stem cell reviews and reports · 2026Review
- Human iPSC-Derived Vascularised Lung Organoids for Modelling COPD and Pulmonary Hypertension.Cell proliferation · 2026Article
- Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Hydrogel nanofiber-based 3D cell cultures and organoids.Chemical science · 2026Review
- Advances in vascularized organoids.Chinese medical journal · 2026Review
- Biofabrication for spatial control of multiscale biological crosstalk in tissue models.npj biomedical innovations · 2026Review
- Vascularized bone organoids: current advances and a biomimetic platform for osteonecrosis of the femoral head.Bone research · 2026Review
- Review
- Endothelial Continuum and Capillary Specialization in Pulmonary Vascular Development.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Stem cell-based tactics in the remodeling and treatment of intestinal diseases.Stem cell research & therapy · 2026Review
- Disease modelling with in vitro vascularised organoids.Disease models & mechanisms · 2026Review
- Mesoscale maladaptation in disease organoids.Disease models & mechanisms · 2026Article
- Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones.Materials today. Bio · 2026Review
- Progenitor Resilience and the Early Onset of Chronic Lung Diseases: NHLBI workshop report.American journal of respiratory cell and molecular biology · 2026Article
- Organoids: generation strategies, applications, and future challenges.Stem cell research & therapy · 2026Review
- Article
- Advances in our understanding of distal progenitors in idiopathic pulmonary fibrosis: implications for novel therapeutics.The European respiratory journal · 2026Review
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Authors and funding
30 authors.
Yifei MiaoDivision of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA. Electronic address: yifei.miao@ioz.ac.cn.
Nicole M PekDivision of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA.
Cheng TanDivision of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA.
Cheng JiangDivision of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Zhiyun YuDivision of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA.
Kentaro IwasawaCenter for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA.
Min ShiCenter for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Nephrology and Hypertension, CCHMC, Cincinnati, OH 45229, USA.
Daniel O KecheleDivision of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA.
Nambirajan SundaramDivision of Pediatric General and Thoracic Surgery, CCHMC, Cincinnati, OH 45229, USA.
Victor Pastrana-GomezDivision of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA.
Debora I SinnerDivision of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Xingchen LiuDivision of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
Ko Chih LinDivision of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
Cheng-Lun NaDivision of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Keishi KishimotoCenter for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA.
Min-Chi YangDepartment of Cell, Developmental, and Regenerative Biology, Department of Otolaryngology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sushila MaharjanDivision of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
Jason TchieuCenter for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA.
Jeffrey A WhitsettDivision of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Yu Shrike ZhangDivision of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kyle W McCrackenCenter for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Nephrology and Hypertension, CCHMC, Cincinnati, OH 45229, USA.
Robbert J RottierDepartment of Cell Biology, Erasmus MC, Rotterdam, the Netherlands; Department of Pediatric Surgery, Sophia Children's Hospital, Wytemaweg 80, 3015 CN Rotterdam, the Netherlands.
Darrell N KottonPulmonary Center, Department of Medicine, Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA.
Michael A HelmrathDivision of Pediatric General and Thoracic Surgery, CCHMC, Cincinnati, OH 45229, USA.
James M WellsCenter for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Endocrinology, CCHMC, Cincinnati, OH 45229, USA.
Takanori TakebeCenter for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Gastroenterology, Hepatology & Nutrition, CCHMC, Cincinnati, OH 45229, USA; Department of Genome Biology and WPI Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka University, Osaka 565-0871, Japan.
Aaron M ZornCenter for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA.
Ya-Wen ChenDepartment of Cell, Developmental, and Regenerative Biology, Department of Otolaryngology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Minzhe GuoDivision of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. Electronic address: minzhe.guo@cchmc.org.
Mingxia GuDivision of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. Electronic address: mgu@mednet.ucla.edu.
Funding
ENVIRONMETAL CARCINOGENESIS AND MUTAGENESIST32ES007250 · NIEHS · UNIVERSITY OF CINCINNATI · PI MILLER, WILLIAM E · 1988 to 2024
$11.9MPediatric Center--Gene Expression /Developmental ScienceK12HD028827 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI Tina Lee Cheng · 2002 to 2026
$9.6MElucidating the FOXF1 gene regulatory network in human alveologenesisR01HL166283 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Mingxia Gu · 2023 to 2026
$1.9MNHLBI NIH HHS R01 HL166283NICHD NIH HHS K12 HD028827NIEHS NIH HHS T32 ES007250
Abstract
The vasculature and mesenchyme exhibit distinct organ-specific characteristics adapted to local physiological needs, shaped by microenvironmental and cell-cell interactions from early development. To recapitulate this entire process, we co-differentiated mesoderm and endoderm within the same spheroid to vascularize lung and intestinal organoids from induced pluripotent stem cells (iPSCs). Bone morphogenetic protein (BMP) signaling fine-tuned the endoderm-to-mesoderm ratio, a critical step in generating appropriate proportions of endothelial and epithelial progenitors with tissue specificity. Single-cell RNA sequencing (scRNA-seq) revealed organ-specific gene signatures of endothelium and mesenchyme and identified key ligands driving endothelial specification. The endothelium exhibited tissue-specific barrier function, enhanced organoid maturation, cellular diversity, and alveolar formation on the engineered lung scaffold. Upon transplantation into mice, the organoid vasculature integrated with the host circulation while preserving organ specificity, further promoting organoid maturation. Leveraging these vascularized organoids, we uncovered abnormal endothelial-epithelial crosstalk in patients with forkhead box F1 (FOXF1) mutations. Multilineage organoids provide an advanced platform to study intricate cell-to-cell communications in human organogenesis and disease.
Indexed as
EndodermIntestinesLungMesodermNeovascularization, PhysiologicOrganoidsAnimalsBone Morphogenetic ProteinsCell DifferentiationEndothelial CellsForkhead Transcription FactorsHumansInduced Pluripotent Stem CellsMiceOrganogenesisBone Morphogenetic ProteinsForkhead Transcription Factorsco-differentiationendodermFOXF1intestinelungmesenchymemesodermorganoidorgan-specific endotheliumvascularization
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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 Socratic graph.