Evidence map›Paper›PMID 25998005›Full record

ArticleStem cell research & therapy2015

Endothelial cells direct human mesenchymal stem cells for osteo- and chondro-lineage differentiation through endothelin-1 and AKT signaling.

Tsung-Lin Tsai, Bowen Wang, Matthew W Squire, Lian-Wang Guo, Wan-Ju Li

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 2 pooled it
3.8field-weighted citation impact, top 6% 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

33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
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  20. Endothelin-1 differentially directs lineage specification of adipose- and bone marrow-derived mesenchymal stem cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
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

5 authors at 1 institution in 1 country.

Tsung-Lin TsaiDepartment of Orthopedics and Rehabilitation, Laboratory of Musculoskeletal Biology and Regenerative Medicine, University of Wisconsin-Madison, 1111 Highland Ave, WIMR 5051, Madison, WI, 53705, USA. tsai@ortho.wisc.edu.
Bowen WangDepartment of Surgery, University of Wisconsin-Madison, 1111 Highland Ave, WIMR 5151, Madison, WI 53705, USA. WANGB@surgery.wisc.edu.
Matthew W SquireDepartment of Orthopedics and Rehabilitation, Laboratory of Musculoskeletal Biology and Regenerative Medicine, University of Wisconsin-Madison, 1111 Highland Ave, WIMR 5051, Madison, WI, 53705, USA. Squire@ortho.wisc.edu.
Lian-Wang GuoDepartment of Surgery, University of Wisconsin-Madison, 1111 Highland Ave, WIMR 5151, Madison, WI 53705, USA. GUO@surgery.wisc.edu.
Wan-Ju LiDepartment of Orthopedics and Rehabilitation, Laboratory of Musculoskeletal Biology and Regenerative Medicine, University of Wisconsin-Madison, 1111 Highland Ave, WIMR 5051, Madison, WI, 53705, USA. li@ortho.wisc.edu.
University of Wisconsin–Madison · US

Funding

Sigma-1 Chaperone-Mediated in vivo Neuroprotection in the RetinaR01EY022678 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI GUO, LIANWANG · 2012 to 2016
$1.7M
NEI NIH HHS R01 EY022678
6 · The paper itself

Abstract

introductionHuman mesenchymal stem cells (hMSCs) reside in a perivascular niche of the body, suggesting that they interact closely with vascular endothelial cells (ECs) through cell-cell interaction or paracrine signaling to maintain cell functions. Endothelin-1 (ET1) is a paracrine factor mainly secreted by ECs. We thus hypothesize that ECs can regulate cellular activities of hMSCs and direct their stem cell fate.

methodsWe investigated whether co-cultured human aortic endothelial cells (HAECs) were able to regulate expression of potency- and lineage-related markers in bone marrow-derived hMSCs. We further explored the regulatory effects of ET1 on cell proliferation, expression of surface antigens and pluripotency-related markers, and multilineage differentiation in hMSCs. Activation of the AKT signaling pathway in hMSCs was also analyzed to identify its mechanistic role in the ET1-induced regulation.

resultsCo-cultured HAECs enhanced expression of mesenchymal lineage-related markers in hMSCs. Treatment of ET receptor antagonist downregulated the increased expression of CBFA1 in hMSCs cultured with HAEC-conditioned medium. hMSCs treated with ET1 showed cell proliferation and expression of surface antigens, CD73, CD90, and CD105, comparable with those without ET1 treatment. ET1-treated hMSCs also expressed upregulated mRNA transcript levels of OCT3/4, NANOG, CBFA1 and SOX9. When induced for lineage-specific differentiation, hMSCs pre-treated with ET1 showed enhanced osteogenesis and chondrogenesis. However, adipogenic differentiation of hMSCs was not affected by ET1 pretreatment. We further showed that the ET1-induced regulation was mediated by activation of AKT signaling.

conclusionOur results demonstrate that ET1 secreted by HAECs can direct bone marrow-derived hMSCs for osteo- and chondro-lineage differentiation through activation of the AKT signaling pathway, suggesting that ET1 plays a crucial role in regulation of hMSC activity. Our findings may help understand how hMSCs interact with ECs in a perivascular niche.

Indexed as

Antigens, CDAortaBone Marrow CellsCell DifferentiationCell LineageCell ProliferationCells, CulturedChondrogenesisCoculture TechniquesCore Binding Factor Alpha 1 SubunitCulture Media, ConditionedDown-RegulationEndothelial CellsEndothelin-1HumansMesenchymal Stem CellsAntigens, CDCore Binding Factor Alpha 1 SubunitCulture Media, ConditionedEndothelin-1Proto-Oncogene Proteins c-aktTranscription Factors

Identifiers

PMID25998005
PMCPMC4416238
OpenAlexW2117004813

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.