Evidence map›Paper›PMID 36252111›Full record

ArticleCirculation research2022

Intrapericardial Exosome Therapy Dampens Cardiac Injury via Activating Foxo3.

Dashuai Zhu, Shuo Liu, Ke Huang, Zhenzhen Wang, Shiqi Hu, Junlang Li, Zhenhua Li, Ke Cheng

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

86 citing papers in PubMed, 96 citations in OpenAlex.

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26 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

Dashuai Zhu *Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC (D.Z., S.L., K.H., Z.W., S.H., J.L., Z.L., K.C.).ORCID 0000-0002-4645-5786
Shuo Liu *Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC (D.Z., S.L., K.H., Z.W., S.H., J.L., Z.L., K.C.).ORCID 0000-0002-2969-5876
Ke Huang *Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC (D.Z., S.L., K.H., Z.W., S.H., J.L., Z.L., K.C.).ORCID 0000-0002-9355-7224
Zhenzhen WangDepartment of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC (D.Z., S.L., K.H., Z.W., S.H., J.L., Z.L., K.C.).ORCID 0000-0002-5245-6726
Shiqi HuDepartment of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC (D.Z., S.L., K.H., Z.W., S.H., J.L., Z.L., K.C.).ORCID 0000-0002-8570-3439
Junlang LiDepartment of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC (D.Z., S.L., K.H., Z.W., S.H., J.L., Z.L., K.C.).ORCID 0000-0002-5739-5168
Zhenhua LiDepartment of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC (D.Z., S.L., K.H., Z.W., S.H., J.L., Z.L., K.C.).
Ke ChengDepartment of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC (D.Z., S.L., K.H., Z.W., S.H., J.L., Z.L., K.C.).ORCID 0000-0001-8053-7059
North Carolina State University · USUniversity of North Carolina Health Care · US

Funding

Targeted Nanoparticles for Stem Cell Redirecting and Regenerative MedicineR01HL123920 · NHLBI · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI CHENG, KE · 2015 to 2023
$4.8M
Harnessing Platelet-Endothelial Interactions for Stem Cell DeliveryR01HL144002 · NHLBI · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI Ke Cheng · 2019 to 2026
$4.5M
Modulating Exosome Cargos and Surfaces for Precision Heart RepairR01HL146153 · NHLBI · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI Ke Cheng · 2019 to 2026
$4.2M
Drug Delivery and Biomimetic Approaches for Optimal Stem Cell TherapyR01HL154154 · NHLBI · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI CHENG, KE · 2021 to 2024
$3.1M
Surgical Microneedle Patch Delivery of CMMP for Heart RepairR01HL149940 · NHLBI · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI CHENG, KE · 2020 to 2023
$3.0M
Cardiac Patches Loaded with Stem Cell Factors to Treat Heart FailureR01HL147357 · NHLBI · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI CHENG, KE · 2019 to 2022
$2.7M
Enhancing vascular delivery of stem cells and microparticlesR01HL137093 · NHLBI · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI CHENG, KE · 2017 to 2020
$1.5M
NHLBI NIH HHS R01 HL123920NHLBI NIH HHS R01 HL137093NHLBI NIH HHS R01 HL144002NHLBI NIH HHS R01 HL146153NHLBI NIH HHS R01 HL147357NHLBI NIH HHS R01 HL149940NHLBI NIH HHS R01 HL154154
6 · The paper itself

Abstract

backgroundMesenchymal stem cell (MSC)-derived exosomes are well recognized immunomodulating agents for cardiac repair, while the detailed mechanisms remain elusive. The Pericardial drainage pathway provides the heart with immunosurveillance and establishes a simplified model for studying the mechanisms underlying the immunomodulating effects of therapeutic exosomes.

methodsMyocardial infarction (MI) models with and without pericardiectomy (corresponding to Tomy MI and NonTomy MI) were established to study the functions of pericardial drainage pathway in immune activation of cardiac-draining mediastinal lymph node (MLN). Using the NonTomy MI model, MSC exosomes or vehicle PBS was intrapericardially injected for MI treatment. Via cell sorting and RNA-seq (RNA-sequencing) analysis, the differentially expressed genes were acquired for integrated pathway analysis to identify responsible mechanisms. Further, through functional knockdown/inhibition studies, application of cytokines and neutralizing antibodies, western blot, flow cytometry, and cytokine array, the molecular mechanisms were studied. In addition, the therapeutic efficacy of intrapericardially injected exosomes for MI treatment was evaluated through functional and histological analyses.

resultsWe show that the pericardial draining pathway promoted immune activation in the MLN following MI. Intrapericardially injected exosomes accumulated in the MLN and induced regulatory T cell differentiation to promote cardiac repair. Mechanistically, uptake of exosomes by major histocompatibility complex (MHC)-II

conclusionsThis study reveals a novel mechanism underlying the immunomodulation effects of MSC exosomes and provides a promising candidate (PP2A/p-Akt/Foxo3 signaling pathway) with a favorable delivery route (intrapericardial injection) for cardiac repair.

Indexed as

ExosomesHeart InjuriesMesenchymal Stem CellsMyocardial InfarctionForkhead Box Protein O3HumansProto-Oncogene Proteins c-aktSignal TransductionForkhead Box Protein O3FOXO3 protein, humanProto-Oncogene Proteins c-aktexosomesimmunomodulationmesesnchymal stem cellmyocardial infarctionregulatory T cell

Identifiers

PMID36252111
PMCPMC9667926
OpenAlexW4306175132

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.