Evidence map›Paper›PMID 34303155›Full record

ArticleBiomaterials2021

A robust vasculogenic microfluidic model using human immortalized endothelial cells and Thy1 positive fibroblasts.

Zhengpeng Wan, Shun Zhang, Amy X Zhong, Sarah E Shelton, Marco Campisi, Shriram K Sundararaman, Giovanni S Offeddu, Eunkyung Ko, Lina Ibrahim, Mark F Coughlin and 4 more

Open access · greenAbstract read
In one paragraph

Article in Biomaterials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

41 citing papers in PubMed, 54 citations in OpenAlex.

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  16. Ether lipids influence cancer cell fate by modulating iron uptake.bioRxiv : the preprint server for biology · 2025
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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

14 authors at 3 institutions in 2 countries.

Zhengpeng WanDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Shun ZhangDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Amy X ZhongDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Sarah E SheltonDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Marco CampisiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA; Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, 10129, Italy.
Shriram K SundararamanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Giovanni S OffedduDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Eunkyung KoDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Lina IbrahimDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Mark F CoughlinDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Tiankun LiuDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA; Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.
Jing BaiDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
David A BarbieDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. Electronic address: david_barbie@dfci.harvard.edu.
Roger D KammDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. Electronic address: rdkamm@mit.edu.
Massachusetts Institute of Technology · USDana-Farber Cancer Institute · USPolitecnico di Torino · IT

Funding

Development of Physiologic Tissue Models to Assess Tumor Explant Response to Immune Checkpoint BlockadeU01CA214381 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BARBIE, DAVID A, KAMM, ROGER D · 2017 to 2021
$3.5M
Imaging Cancer Angiogenesis with Acoustic Angiography UltrasoundK00CA212227 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SHELTON, SARAH ELIZABETH · 2018 to 2021
$392k
NCI NIH HHS K00 CA212227NCI NIH HHS U01 CA214381
6 · The paper itself

Abstract

Human umbilical vein endothelial cells (HUVECs) and stromal cells, such as human lung fibroblasts (FBs), have been widely used to generate functional microvascular networks (μVNs) in vitro. However, primary cells derived from different donors have batch-to-batch variations and limited lifespans when cultured in vitro, which hampers the reproducibility of μVN formation. Here, we immortalize HUVECs and FBs by exogenously expressing human telomerase reverse transcriptase (hTERT) to obtain stable endothelial cell and FB sources for μVN formation in vitro. Interestingly, we find that immortalized HUVECs can only form functional μVNs with immortalized FBs from earlier passages but not from later passages. Mechanistically, we show that Thy1 expression decreases in FBs from later passages. Compared to Thy1 negative FBs, Thy1 positive FBs express higher IGFBP2, IGFBP7, and SPARC, which are important for angiogenesis and lumen formation during vasculogenesis in 3D. Moreover, Thy1 negative FBs physically block microvessel openings, reducing the perfusability of μVNs. Finally, by culturing immortalized FBs on gelatin-coated surfaces in serum-free medium, we are able to maintain the majority of Thy1 positive immortalized FBs to support perfusable μVN formation. Overall, we establish stable cell sources for μVN formation and characterize the functions of Thy1 positive and negative FBs in vasculogenesis in vitro.

Indexed as

MicrofluidicsTelomeraseCell DifferentiationCells, CulturedFibroblastsHumansHuman Umbilical Vein Endothelial CellsReproducibility of ResultsTelomeraseFibroblastsHUVECsImmortalizationMicrofluidicThy1Vasculogenesis

Identifiers

PMID34303155
PMCPMC9891349
OpenAlexW3186135580

What OpenQuestion holds

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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 OpenQuestion graph.