Evidence mapPaperPMID 40121529Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

AAT-MSC-EVs: Novel implications for suppressing ferroptosis, fibrosis and pain associated with chronic pancreatitis.

Sara Shoeibi, Wenyu Gou, Tiffany Yeung, Kristi Helke, Erica Green, Charlie Strange, Hongjun Wang

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. 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

7 authors.

Sara ShoeibiDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Wenyu GouDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Tiffany YeungDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Kristi HelkeDepartment of Comparative Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Erica GreenDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Charlie StrangeDepartment of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Hongjun WangDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: wangho@musc.edu.

Funding

Autologous BM-MSCs and Islet Co-transplantation to Enhance Islet Survival and Function in TP-IAT PatientsR01DK126454 · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2025 to 2025
$641k
Cellular Therapy for Type 1 Diabetes using Mesenchymal Stem CellsR01DK118529 · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2025 to 2025
$634k
Safety and Efficacy of Mesenchymal Stem Cells in the Treatment of Chronic Pancreatitis and Its Associated PainUH3DK136705 · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2025 to 2025
$395k
NIDDK NIH HHS R01 DK105183NIDDK NIH HHS R01 DK118529NIDDK NIH HHS R01 DK120394NIDDK NIH HHS R01 DK126454NIDDK NIH HHS UH3 DK136705
6 · The paper itself

Abstract

Chronic pancreatitis (CP) is characterized by inflammation, acinar cell death, fibrosis, and persistent pain. We investigated mesenchymal stem/stromal cell (MSC)-derived extracellular vesicles (EVs) for CP treatment. CP was modeled in male mice using bile duct TNBS infusion, and pancreatic tissues from CP patients were also analyzed. EVs from immortalized human MSCs overexpressing alpha-1 antitrypsin (iAAT-MSCs) were tested for their effects on ferroptosis, fibrosis, and pain. CP tissues showed reduced glutathione peroxidase 4 (GPx4) activity (p < 0.05) and iron accumulation, indicating ferroptosis. iMSC and iAAT-MSC-EVs alleviated CP symptoms by suppressing ferroptosis, restoring GPx4 activity, reducing MDA levels, and mitigating fibrosis markers (α-smooth muscle actin, transforming growth factor-β1, matrix metalloproteinase 2). EV treatment also alleviated pain by decreasing macrophage and mast cell infiltration into the pancreas and dorsal root ganglia while reducing pain-related gene expression (TRVP1, TacR1, Necab3). Additionally, iAAT-MSC-EVs were distinct in cytokine signaling, PI3K-Akt pathway activation, and upregulation of miRNAs like miR-9, miR-10a-5p, miR-92a, miR-200, miR-370, and miR-146a. These results suggest ferroptosis as a key mechanism in CP and highlight the therapeutic potential of iAAT-MSC-EVs in addressing ferroptosis, fibrosis, and pain, presenting a promising, cell-free therapeutic strategy for CP.

Indexed as

Extracellular VesiclesFerroptosisMesenchymal Stem CellsPainPancreatitis, ChronicAnimalsDisease Models, AnimalFibrosisHumansMaleMiceMicroRNAsSignal TransductionMicroRNAsalpha-1 antitrypsinchronic pancreatitisEV therapyferroptosisfibrosismesenchymal stem cellsmiRNAspain

Identifiers

PMID40121529
PMCPMC12266032

What Socratic holds

Textmetadata
Read underepoch 390

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 Socratic graph.