Evidence map›Paper›PMID 38908380›Full record

ArticleCell stem cell2024

Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms.

Shira Landau, Yimu Zhao, Homaira Hamidzada, Gregory M Kent, Sargol Okhovatian, Rick Xing Ze Lu, Chuan Liu, Karl T Wagner, Krisco Cheung, Sarah A Shawky and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing 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

57 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Shira LandauInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Yimu ZhaoInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Homaira HamidzadaToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada.
Gregory M KentMcEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Sargol OkhovatianInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Rick Xing Ze LuInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Chuan LiuInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Karl T WagnerInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada.
Krisco CheungDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada.
Sarah A ShawkyDepartment of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Daniel VosoughiToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Erika Leigh BeroncalDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Ian FernandesMcEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Carolyn L CumminsDepartment of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Banting and Best Diabetes Centre, Toronto, ON, Canada; The Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto, ON, Canada.
Ana C AndreazzaDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Addiction and Mental Health, Toronto, ON, Canada.
Gordon M KellerMcEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Slava EpelmanToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada; Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. Electronic address: slava.epelman@uhn.ca.
Milica RadisicInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada; Terrence Donnelly Centre for Cellular & Biomolecular Research, 160 College St, Toronto, ON M5S 3E1, Canada. Electronic address: m.radisic@utoronto.ca.

Funding

Engineering Vascularized Cardiac MuscleR01HL076485 · NHLBI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Gordana Vunjak-Novakovic · 2005 to 2026
$9.2M
NHLBI NIH HHS R01 HL076485
6 · The paper itself

Abstract

The intricate anatomical structure and high cellular density of the myocardium complicate the bioengineering of perfusable vascular networks within cardiac tissues. In vivo neonatal studies highlight the key role of resident cardiac macrophages in post-injury regeneration and angiogenesis. Here, we integrate human pluripotent stem-cell-derived primitive yolk-sac-like macrophages within vascularized heart-on-chip platforms. Macrophage incorporation profoundly impacted the functionality and perfusability of microvascularized cardiac tissues up to 2 weeks of culture. Macrophages mitigated tissue cytotoxicity and the release of cell-free mitochondrial DNA (mtDNA), while upregulating the secretion of pro-angiogenic, matrix remodeling, and cardioprotective cytokines. Bulk RNA sequencing (RNA-seq) revealed an upregulation of cardiac maturation and angiogenesis genes. Further, single-nuclei RNA sequencing (snRNA-seq) and secretome data suggest that macrophages may prime stromal cells for vascular development by inducing insulin like growth factor binding protein 7 (IGFBP7) and hepatocyte growth factor (HGF) expression. Our results underscore the vital role of primitive macrophages in the long-term vascularization of cardiac tissues, offering insights for therapy and advancing heart-on-a-chip technologies.

Indexed as

Lab-On-A-Chip DevicesMacrophagesNeovascularization, PhysiologicHeartHepatocyte Growth FactorHumansMyocardiumHepatocyte Growth Factorblood vesselscardiac tissuecardiomyocyteendothelial cellsmyocardiumorgan-on-a-chippluripotent stem cellprimitive macrophagesresident macrophagevascularization

Identifiers

PMID38908380
PMCPMC11297673

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.