Evidence map›Paper›PMID 22036563›Full record

ArticleCell2011

Endothelial-derived angiocrine signals induce and sustain regenerative lung alveolarization.

Bi-Sen Ding, Daniel J Nolan, Peipei Guo, Alexander O Babazadeh, Zhongwei Cao, Zev Rosenwaks, Ronald G Crystal, Michael Simons, Thomas N Sato, Stefan Worgall and 3 more

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04057833 (A Phase 1 Open-Label, Single-Center Investigator Initiated Trial), which is not on this map. Cited by 326 papers.

0numbers the graph read from it
0cells of the map it votes in
326citing papers in PubMed
26.9field-weighted citation impact, top 1% of its field
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.

NCT04057833 phase1active not recruitingnot on this mapstarted 2019, after this paper: background citation

A Phase 1 Open-Label, Single-Center Investigator Initiated Trial (IIT) of E-CEL UVEC Cells as an Adjunct Cell Therapy for the Arthroscopic Rotator Cuff Repair in Adults

TypeinterventionalSponsorHospital for Special Surgery, New YorkRan2019 to 2026Enrolled20ConditionsRotator Cuff Tears, Muscle Atrophy or Weakness, Tendon Rupture - Shoulder, Safety IssuesArmsE-CEL UVEC
3 · Its place in the literature

Who cites it

326 citing papers in PubMed, 498 citations in OpenAlex.

  1. Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
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266 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Bi-Sen DingAnsary Stem Cell Institute, Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Daniel J Nolan
Peipei Guo
Alexander O Babazadeh
Zhongwei Cao
Zev Rosenwaks
Ronald G Crystal
Michael Simons
Thomas N Sato
Stefan Worgall
Koji Shido
Sina Y Rabbany
Shahin Rafii
Cornell University · USHoward Hughes Medical Institute · USNara Institute of Science and Technology · JPYale University · US

Funding

Role of Alveolar Macrophages in the Accelerated Emphysema of HIV-1 PositiveP50HL084936 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CRYSTAL, RONALD G · 2007 to 2011
$14.2M
Angiogensis and ischemiaR01HL053793 · NHLBI · YALE UNIVERSITY · PI SIMONS, MICHAEL · 1996 to 2017
$7.3M
Dynamic regulation of the epigenome during hematopoietic differntiationRC2HL101846 · NHLBI · COLD SPRING HARBOR LABORATORY · PI GINGERAS, THOMAS RAYMOND, HANNON, GREGORY J · 2009 to 2010
$2.5M
Contribution of the vascular niche to the hematopoietic reconstitution.R01HL097797 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI RAFII, SHAHIN · 2009 to 2012
$1.7M
Reconstitution of thrombopoiesis by angiogenic factorsRC1AI080309 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI RAFII, SHAHIN · 2009 to 2009
$500k
Howard Hughes Medical InstituteNHLBI NIH HHS P50 HL084936NHLBI NIH HHS R01 HL053793NHLBI NIH HHS R01 HL097797NHLBI NIH HHS R01HL53793NHLBI NIH HHS RC2 HL101846NIAID NIH HHS RC1 AI080309
6 · The paper itself

Abstract

To identify pathways involved in adult lung regeneration, we employ a unilateral pneumonectomy (PNX) model that promotes regenerative alveolarization in the remaining intact lung. We show that PNX stimulates pulmonary capillary endothelial cells (PCECs) to produce angiocrine growth factors that induce proliferation of epithelial progenitor cells supporting alveologenesis. Endothelial cells trigger expansion of cocultured epithelial cells, forming three-dimensional angiospheres reminiscent of alveolar-capillary sacs. After PNX, endothelial-specific inducible genetic ablation of Vegfr2 and Fgfr1 in mice inhibits production of MMP14, impairing alveolarization. MMP14 promotes expansion of epithelial progenitor cells by unmasking cryptic EGF-like ectodomains that activate the EGF receptor (EGFR). Consistent with this, neutralization of MMP14 impairs EGFR-mediated alveolar regeneration, whereas administration of EGF or intravascular transplantation of MMP14(+) PCECs into pneumonectomized Vegfr2/Fgfr1-deficient mice restores alveologenesis and lung inspiratory volume and compliance function. VEGFR2 and FGFR1 activation in PCECs therefore increases MMP14-dependent bioavailability of EGFR ligands to initiate and sustain alveologenesis.

Indexed as

AnimalsEndothelial CellsEndothelial Growth FactorsEpithelial CellsLungMatrix Metalloproteinase 14MiceMice, KnockoutNeovascularization, PhysiologicPneumonectomyPulmonary AlveoliReceptor, Fibroblast Growth Factor, Type 1RegenerationStem CellsTissue Culture TechniquesVascular Endothelial Growth Factor Receptor-2Endothelial Growth FactorsMatrix Metalloproteinase 14Mmp14 protein, mouseReceptor, Fibroblast Growth Factor, Type 1Vascular Endothelial Growth Factor Receptor-2

Identifiers

PMID22036563
PMCPMC3228268
OpenAlexW2006464386

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.