Evidence map›Paper›PMID 39429777›Full record

ArticleiScience2024

GPC3-mediated metabolic rewiring of diabetic mesenchymal stromal cells enhances their cardioprotective functions via PKM2 activation.

Darukeshwara Joladarashi, Charan Thej, Vandana Mallaredy, Ajit Magadum, Maria Cimini, Carolina Gonzalez, May Truongcao, Joseph T Nigro, Manveen K Sethi, Andrew A Gibb and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Review
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

13 authors.

Darukeshwara JoladarashiAging and Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Charan ThejAging and Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Vandana MallaredyAging and Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Ajit MagadumAging and Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Maria CiminiAging and Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Carolina GonzalezAging and Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
May TruongcaoAging and Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Joseph T NigroCenter for Biomedical Mass Spectrometry, Department of Biochemistry & Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
Manveen K SethiCenter for Biomedical Mass Spectrometry, Department of Biochemistry & Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
Andrew A GibbCenter for Cardiometabolic Science, Christina Lee Brown Envirome Institute, University of Louisville, 580 South Preston Street, Louisville, KY, USA.
Cindy BenedictAging and Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Walter J KochDepartment of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
Raj KishoreAging and Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.

Funding

Small and large animal surgery, physiology and histologyP01HL134608 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI Douglas Tilley · 2017 to 2026
$21.0M
Targeting Pathways Involved in Cardiac Injury for Novel Repair StrategiesP01HL147841 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI ELROD, JOHN WILLIAM · 2020 to 2024
$11.4M
Restoration of myocardial reparative function of diabetic progenitor cells by epigenetic modulationR01HL143892 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KISHORE, RAJ · 2020 to 2023
$2.2M
MyomiR-499, Exosomes and Endothelial and Endothelial Progenitor Cells dysfunction in DiabetesR01HL169405 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI Raj Kishore · 2024 to 2026
$1.8M
NHLBI NIH HHS P01 HL134608NHLBI NIH HHS P01 HL147841NHLBI NIH HHS R01 HL143892NHLBI NIH HHS R01 HL169405
6 · The paper itself

Abstract

Mesenchymal stromal cells (MSC) are promising stem cell therapy for treating cardiovascular and other degenerative diseases. Diabetes affects the functional capability of MSC and impedes cell-based therapy. Despite numerous studies, the impact of diabetes on MSC myocardial reparative activity, metabolic fingerprint, and the mechanism of dysfunction remains inadequately perceived. We demonstrated that the transplantation of diabetic-MSC (db/db-MSC) into the ischemic myocardium of mice does not confer cardiac benefit post-MI. Metabolomic studies identified defective energy metabolism in db/db-MSC. Furthermore, we found that glypican-3 (GPC3), a heparan sulfate proteoglycan, is highly upregulated in db/db-MSC and is involved in metabolic alterations in db/db-MSC via pyruvate kinase M2 (PKM2) activation. GPC3-knockdown reprogrammed-db/db-MSC restored their energy metabolic rates, immunomodulation, angiogenesis, and cardiac reparative activities. Together, these data indicate that GPC3-metabolic reprogramming in diabetic MSC may represent a strategy to enhance MSC-based therapeutics for myocardial repair in diabetic patients.

Indexed as

Cell biologyMetabolomicsMolecular biologyProteomics

Identifiers

PMID39429777
PMCPMC11490746

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.