Evidence map›Paper›PMID 32807231›Full record

ArticleStem cell research & therapy2020

A transcriptomic analysis of serial-cultured, tonsil-derived mesenchymal stem cells reveals decreased integrin α3 protein as a potential biomarker of senescent cells.

Da Hyeon Choi, Se-Young Oh, Ju Kwang Choi, Kyeong Eun Lee, Ju Yeon Lee, Yoon Jeong Park, Inho Jo, Yoon Shin Park

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

9 citing papers in PubMed, 18 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

8 authors at 3 institutions in 1 country.

Da Hyeon ChoiDepartment of Microbiology, School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, 28644, Republic of Korea.
Se-Young OhDepartment of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul, 07804, Republic of Korea.
Ju Kwang ChoiDepartment of Microbiology, School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, 28644, Republic of Korea.
Kyeong Eun LeeDepartment of Microbiology, School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, 28644, Republic of Korea.
Ju Yeon LeeCentral Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), School of Dentistry, Seoul National University, Seoul, 03080, Republic of Korea.
Yoon Jeong ParkCentral Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), School of Dentistry, Seoul National University, Seoul, 03080, Republic of Korea.ORCID 0000-0002-5373-9218
Inho JoDepartment of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul, 07804, Republic of Korea.
Yoon Shin ParkDepartment of Microbiology, School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, 28644, Republic of Korea. pys@cbnu.ac.kr.
Chungbuk National University · KRSeoul National University · KREwha Womans University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMesenchymal stem cells (MSCs) have been widely used for stem cell therapy, and serial passage of stem cells is often required to obtain sufficient cell numbers for practical applications in regenerative medicine. A long-term serial cell expansion can potentially induce replicative senescence, which leads to a progressive decline in stem cell function and stemness, losing multipotent characteristics. To improve the therapeutic efficiency of stem cell therapy, it would be important to identify specific biomarkers for senescent cells.

methodsTonsil-derived mesenchymal stem cells (TMSCs) with 20-25 passages were designated as culture-aged TMSCs, and their mesodermal differentiation potentials as well as markers of senescence and stemness were compared with the control TMSCs passaged up to 8 times at the most (designated as young). A whole-genome analysis was used to identify novel regulatory factors that distinguish between the culture-aged and control TMSCs. The identified markers of replicative senescence were validated using Western blot analyses.

resultsThe culture-aged TMSCs showed longer doubling time compared to control TMSCs and had higher expression of senescence-associated (SA)-β-gal staining but lower expression of the stemness protein markers, including Nanog, Oct4, and Sox2 with decreased adipogenic, osteogenic, and chondrogenic differentiation potentials. Microarray analyses identified a total of 18,614 differentially expressed genes between the culture-aged and control TMSCs. The differentially expressed genes were classified into the Gene Ontology categories of cellular component (CC), functional component (FC), and biological process (BP) using KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis. This analysis revealed that those genes associated with CC and BP showed the most significant difference between the culture-aged and control TMSCs. The genes related to extracellular matrix-receptor interactions were also shown to be significantly different (p < 0.001). We also found that culture-aged TMSCs had decreased expressions of integrin α3 (ITGA3) and phosphorylated AKT protein (p-AKT-Ser

conclusionsOur data suggest that activation of ECM-receptor signaling, specifically involved with integrin family-mediated activation of the intracellular cell survival-signaling molecule AKT, can regulate stem cell senescence in TMSCs. Among these identified factors, ITGA3 was found to be a representative biomarker of the senescent TMSCs. Exclusion of the TMSCs with the senescent TMSC markers in this study could potentially increase the therapeutic efficacy of TMSCs in clinical applications.

Indexed as

Mesenchymal Stem CellsBiomarkersCell DifferentiationCell ProliferationCells, CulturedCellular SenescenceIntegrin alpha3Palatine TonsilTranscriptomeBiomarkersIntegrin alpha3AKTCulture-agedECM-receptor proteinIntegrin α3SenescenceSerial passagingTonsil-derived mesenchymal stem cellsTranscriptome

Identifiers

PMID32807231
PMCPMC7430027
OpenAlexW3049603299

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.