Evidence map›Paper›PMID 29363599›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Human bone perivascular niche-on-a-chip for studying metastatic colonization.

Alessandro Marturano-Kruik, Michele Maria Nava, Keith Yeager, Alan Chramiec, Luke Hao, Samuel Robinson, Edward Guo, Manuela Teresa Raimondi, Gordana Vunjak-Novakovic

Open access · greenAbstract readVideo-Audio Media
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed, 2 pooled it
17.8field-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.

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

111 citing papers in PubMed, 2 syntheses or guidelines pooled it, 219 citations in OpenAlex.

  1. Pooled it
  2. Advances in Engineering Human Tissue Models.Frontiers in bioengineering and biotechnology · 2020
    Pooled it
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Microphysiological systems for metastasis research: a stepwise approach.Cellular oncology (Dordrecht, Netherlands) · 2025
    Review
  11. Review
  12. Review
  13. Review
  14. Exploring bone-tumor interactions through 3DJournal of bone oncology · 2025
    Review
  15. Review
  16. Engineering in vitro vascular microsystems.Microsystems & nanoengineering · 2025
    Review
  17. Article
  18. Microfabricated Organ-Specific Models of Tumor Microenvironments.Annual review of biomedical engineering · 2025
    Review
  19. Article
  20. Article

51 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Alessandro Marturano-KruikDepartment of Biomedical Engineering, Columbia University, New York, NY 10032.
Michele Maria NavaDepartment of Chemistry, Materials and Chemical Engineering "G Natta," Politecnico di Milano, 20133 Milan, Italy.
Keith YeagerDepartment of Biomedical Engineering, Columbia University, New York, NY 10032.
Alan ChramiecDepartment of Biomedical Engineering, Columbia University, New York, NY 10032.
Luke HaoDepartment of Biomedical Engineering, Columbia University, New York, NY 10032.
Samuel RobinsonDepartment of Biomedical Engineering, Columbia University, New York, NY 10032.
Edward GuoDepartment of Biomedical Engineering, Columbia University, New York, NY 10032.
Manuela Teresa RaimondiDepartment of Chemistry, Materials and Chemical Engineering "G Natta," Politecnico di Milano, 20133 Milan, Italy; manuela.raimondi@polimi.it gv2131@columbia.edu.ORCID 0000-0003-2585-7206
Gordana Vunjak-NovakovicDepartment of Biomedical Engineering, Columbia University, New York, NY 10032; manuela.raimondi@polimi.it gv2131@columbia.edu.ORCID 0000-0002-9382-1574
Columbia University · USPolitecnico di Milano · IT

Funding

Translational Bioreactors - Engineering Complex TissuesP41EB002520 · NIBIB · TUFTS UNIVERSITY MEDFORD · PI KAPLAN, DAVID L. · 2004 to 2018
$16.7M
Tissue Chips for Rare Disease: Adding Timothy Syndrome to the HeLIVaSkCa platformUH3EB017103 · NIBIB · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI VUNJAK-NOVAKOVIC, GORDANA · 2014 to 2016
$7.1M
Craniofacial Tissue EngineeringR01DE016525 · NIDCR · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI VUNJAK-NOVAKOVIC, GORDANA · 2005 to 2017
$5.5M
Multi-tissue platform for modeling systemic pathologiesUG3EB025765 · NIBIB · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI VUNJAK-NOVAKOVIC, GORDANA · 2017 to 2019
$2.8M
Integrated heart-liver-vascular systems for drug testing in human health and diseUH2EB017103 · NIBIB · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI VUNJAK-NOVAKOVIC, GORDANA · 2012 to 2013
$1.7M
European Research Council 646990NIBIB NIH HHS P41 EB002520NIBIB NIH HHS UG3 EB025765NIBIB NIH HHS UH2 EB017103NIBIB NIH HHS UH3 EB017103NIDCR NIH HHS R01 DE016525
6 · The paper itself

Abstract

Eight out of 10 breast cancer patients die within 5 years after the primary tumor has spread to the bones. Tumor cells disseminated from the breast roam the vasculature, colonizing perivascular niches around blood capillaries. Slow flows support the niche maintenance by driving the oxygen, nutrients, and signaling factors from the blood into the interstitial tissue, while extracellular matrix, endothelial cells, and mesenchymal stem cells regulate metastatic homing. Here, we show the feasibility of developing a perfused bone perivascular niche-on-a-chip to investigate the progression and drug resistance of breast cancer cells colonizing the bone. The model is a functional human triculture with stable vascular networks within a 3D native bone matrix cultured on a microfluidic chip. Providing the niche-on-a-chip with controlled flow velocities, shear stresses, and oxygen gradients, we established a long-lasting, self-assembled vascular network without supplementation of angiogenic factors. We further show that human bone marrow-derived mesenchymal stem cells, which have undergone phenotypical transition toward perivascular cell lineages, support the formation of capillary-like structures lining the vascular lumen. Finally, breast cancer cells exposed to interstitial flow within the bone perivascular niche-on-a-chip persist in a slow-proliferative state associated with increased drug resistance. We propose that the bone perivascular niche-on-a-chip with interstitial flow promotes the formation of stable vasculature and mediates cancer cell colonization.

Indexed as

Lab-On-A-Chip DevicesBone MatrixBone NeoplasmsBreast NeoplasmsCell Line, TumorCoculture TechniquesDrug Resistance, NeoplasmFemaleHumansMesenchymal Stem CellsOxygenPerfusionTissue ScaffoldsOxygenbone perivascular nichebreast cancerdrug resistancemetastatic colonizationmicrofluidic chip

Identifiers

PMID29363599
PMCPMC5819403
OpenAlexW2789343580

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.