Evidence map›Paper›PMID 32020237›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2020

Spatial localization of endothelial cells in heterotypic spheroids influences Notch signaling.

Charlotte E Vorwald, Shreeya Joshee, J Kent Leach

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

25 citing papers in PubMed, 31 citations in OpenAlex.

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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

3 authors at 2 institutions in 1 country.

Charlotte E VorwaldDepartment of Biomedical Engineering, University of California, Davis, 451 Health Sciences Drive, Davis, CA, 95616, USA.
Shreeya JosheeDepartment of Biomedical Engineering, University of California, Davis, 451 Health Sciences Drive, Davis, CA, 95616, USA.
J Kent LeachDepartment of Biomedical Engineering, University of California, Davis, 451 Health Sciences Drive, Davis, CA, 95616, USA. jkleach@ucdavis.edu.ORCID 0000-0002-1673-3335
University of California, Davis · USUC Davis Health · US

Funding

Training Program In Basic & Translational Cardiovascular ScienceT32HL086350 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Martin Cadeiras, David A. Liem · 2008 to 2026
$7.1M
Biomaterial regulation of cell spheroids to synergistically enhance bone healingR01DE025475 · NIDCR · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEACH, J. KENT · 2015 to 2019
$1.9M
NHLBI NIH HHS T32 HL086350NIDCR NIH HHS R01 DE025475
6 · The paper itself

Abstract

Cell-based therapeutic approaches are an exciting strategy to replenish compromised endothelial cell (EC) populations that contribute to impaired vasculogenesis. Co-cultures of ECs and mesenchymal stromal cells (MSCs) can enhance neovascularization over ECs alone, but the efficacy of cells is limited by rapid cell death upon implantation. Co-culture spheroids exhibit improved survival compared with monodisperse cells, yet little is known about the influence of spatial regulation of ECs within co-culture spheroids. We hypothesized that EC sprouting from co-culture spheroids is a function of EC spatial localization. We formed co-culture spheroids containing ECs and MSCs in two formats: ECs uniformly distributed throughout the spheroid (i.e., mixed) or seeded on the perimeter of the MSC core (i.e., shell). Qualitative observations suggested increased vasculogenesis for mixed co-culture spheroids compared with shell conformations as early as day 3, yet quantitative metrics did not reveal significant differences in network formation between these 3D structures. Notch3 expression demonstrated significant increases in cell-cell communication in mixed conformations compared with shell counterparts. Furthermore, knockdown of Notch3 in MSCs abrogated the vasculogenic potential of mixed spheroids, supporting its role in promoting EC-MSC contacts. This study highlights the direct impact of EC-MSC contacts on sprouting and provides insight to improve the quality of network formation. KEY MESSAGES: • Endothelial cell (EC) localization can be controlled in co-culture EC-MSC spheroids. • Mixed spheroids exhibit consistent networks compared to shell counterparts. • Differences in NOTCH3 were observed between mixed and shell spheroids. • NOTCH3 may be a necessary target for improved vasculogenic potential.

Indexed as

Cell CommunicationCells, CulturedCoculture TechniquesEndothelial CellsHumansMesenchymal Stem CellsNeovascularization, PhysiologicReceptor, Notch3RNA, Small InterferingSignal TransductionSpheroids, CellularNOTCH3 protein, humanReceptor, Notch3RNA, Small InterferingEndothelial cellMesenchymal stromal cellNotchSpheroidsVascularization

Identifiers

PMID32020237
PMCPMC7083693
OpenAlexW3004695784

What OpenQuestion 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 OpenQuestion graph.