Evidence map›Paper›PMID 33853680›Full record

ArticleStem cell research & therapy2021

Hypoxic preconditioning induces epigenetic changes and modifies swine mesenchymal stem cell angiogenesis and senescence in experimental atherosclerotic renal artery stenosis.

Busra Isik, Roman Thaler, Busra B Goksu, Sabena M Conley, Hayder Al-Khafaji, Arjunmohan Mohan, Mohsen Afarideh, Abdelrhman M Abumoawad, Xiang Y Zhu, James D Krier and 8 more

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

Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
11.5field-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

23 citing papers in PubMed, 89 citations in OpenAlex.

  1. Article
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  4. Renovascular Disease and Mitochondrial Dysfunction in Human Mesenchymal Stem Cells.Journal of the American Society of Nephrology : JASN · 2024
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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

18 authors at 3 institutions in 1 country.

Busra Isik *Division of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
Roman Thaler *Department of Biochemistry and Molecular Biology, Rochester, USA.
Busra B GoksuDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
Sabena M ConleyDivision of Nephrology and Hypertension, Mayo Clinic, Jacksonville, FL, USA.
Hayder Al-KhafajiDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
Arjunmohan MohanDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
Mohsen AfaridehDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
Abdelrhman M AbumoawadDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
Xiang Y ZhuDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
James D KrierDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
Ishran M SaadiqDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
Hui TangDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
Alfonso EirinDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
LaTonya J HicksonDivision of Nephrology and Hypertension, Mayo Clinic, Jacksonville, FL, USA.
Andre J van WijnenDepartment of Biochemistry and Molecular Biology, Rochester, USA.
Stephen C TextorDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
Lilach O LermanDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.
Sandra M HerrmannDivision of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA. herrmann.sandra@mayo.edu.ORCID 0000-0002-3700-4537
Mayo Clinic · USGastroenterology Group of Rochester · USMayo Clinic in Florida · US

Funding

Molecular Control of Bone FormationR01AR049069 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI WESTENDORF, JENNIFER J · 2003 to 2021
$5.8M
Hypoxic preconditioning for the improvement of the regenerative capacity of adipose-derived mesenchymal stem cells and its application in chronic kidney disease due to hypertensive nephropathyK08DK118120 · NIDDK · MAYO CLINIC ROCHESTER · PI HERRMANN, SANDRA M · 2018 to 2022
$800k
Noninvasive Evaluation of Renal Allograft Fibrosis by MRIR21AG062104 · NIA · MAYO CLINIC ROCHESTER · PI LERMAN, LILACH O · 2020 to 2021
$414k
Mitochondrial injury interferes with endogenous renal repair in experimental renovascular diseaseR03DK122137 · NIDDK · MAYO CLINIC ROCHESTER · PI EIRIN, ALFONSO · 2019 to 2020
$239k
NIAMS NIH HHS R01 AR049069NIA NIH HHS R21 AG062104NIDDK NIH HHS K08 DK118120NIDDK NIH HHS R03 DK122137
6 · The paper itself

Abstract

backgroundAtherosclerotic renal artery stenosis (ARAS) is a risk factor for ischemic and hypertensive kidney disease (HKD) for which autologous mesenchymal stem cell (MSC) appears to be a promising therapy. However, MSCs from ARAS patients exhibit impaired function, senescence, and DNA damage, possibly due to epigenetic mechanisms. Hypoxia preconditioning (HPC) exerts beneficial effects on cellular proliferation, differentiation, and gene and protein expression. We hypothesized that HPC could influence MSC function and senescence in ARAS by epigenetic mechanisms and modulating gene expression of chromatin-modifying enzymes.

methodsAdipose-derived MSC harvested from healthy control (N = 8) and ARAS (N = 8) pigs were cultured under normoxia (20%O

resultsSpecific pro-angiogenic genes in ARAS assessed by RT-PCR were lower at baseline but increased under HPC, while pro-senescence genes were higher in ARAS at baseline as compared healthy MSCs. ARAS MSCs under basal conditions, displayed higher H3K4me3, H3K27me3, and 5hmC levels compared to healthy MSCs. During HPC, global 5hmC levels were decreased while no appreciable changes occurred in histone H3 tri-methylation. ARAS MSCs cultured under HPC had higher migratory and proliferative capacity as well as increased vascular endothelial growth factor and epidermal growth factor expression compared to normoxia, and SA-β-gal activity decreased in both animal groups.

conclusionsThese data demonstrate that swine ARAS MSCs have decreased angiogenesis and increased senescence compared to healthy MSCs and that HPC mitigates MSC dysfunction, senescence, and DNA hydroxymethylation in ARAS MSC. Thus, HPC for MSCs may be considered for their optimization to improve autologous cell therapy in patients with nephropathies.

Indexed as

Mesenchymal Stem CellsRenal Artery ObstructionAnimalsCells, CulturedEpigenesis, GeneticHumansHypoxiaSwineVascular Endothelial Growth Factor AVascular Endothelial Growth Factor AAdipose mesenchymal stromal cellsAngiogenesisAtherosclerotic renal artery stenosisChromatin organizationEpigeneticsHydroxymethylationHypoxiaMesenchymal stem cellsSenescence

Identifiers

PMID33853680
PMCPMC8048283
OpenAlexW3155402081

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Registered trials

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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.