Evidence map›Paper›PMID 40585231›Full record

ArticleResearch square2025

Pluripotent stem cell-derived extracellular vesicles for systemic immune modulation in diabetes therapy.

Song Li, Jana Zarubova, Mohammad Hasani-Sadrabadi, Yutong Wu, Graciel Diamante, Jenny Cheng, Xiao Han, Fatemeh Majedi, Li Yang, Olivia Wang and 10 more

Abstract readPreprint
In one paragraph

Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

20 authors.

Jana ZarubovaUniversity of California, Los Angeles.
Mohammad Hasani-SadrabadiUniversity of California, Los Angeles.
Yutong WuUniversity of California, Los Angeles.
Graciel DiamanteUniversity of California, Los Angeles.
Jenny ChengUniversity of California, Los Angeles.
Xiao HanUniversity of California, Los Angeles.
Fatemeh MajediUniversity of California, Los Angeles.
Li YangCenter for Cellular and Molecular Diagnostics, Department of Biochemistry and Molecular Biology, Tulane University School of Medicine.ORCID 0000-0002-4710-059X
Olivia WangUniversity of California, Los Angeles.
In Sook AhnUniversity of California, Los Angeles.
Jianyi ZhangUniversity of Alabama at Birmingham.
Xiaojun LianPennsylvania State University.
Zhen GuState Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University.ORCID 0000-0003-2947-4456
Manish ButteUniversity of California Los Angeles.ORCID 0000-0002-4490-5595
Reza ArdehaliUniversity of California, Los Angeles.
Peter ButlerUniversity of California, Los Angeles.
Tony HuTulane University.ORCID 0000-0002-5166-4937
Louis BouchardUCLA.ORCID 0000-0003-4151-5628
Xia YangUniversity of California, Los Angeles.

Funding

Towards Glucose Transporter-Mediated Glucose-Responsive Insulin Delivery with Fast ResponseR01DK112939 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LI, SONG · 2018 to 2022
$2.2M
Nanowired hypoimmunogenic hPSC cardiac organoids for heart repairR01HL175050 · NHLBI · CLEMSON UNIVERSITY · PI XIAOJUN LIAN, Ying Mei · 2024 to 2026
$2.0M
ModRNA-based Direct Programming of Universal Donor hiPSCs into Immune Evasive Beta CellsR56DK133147 · NIDDK · PENNSYLVANIA STATE UNIVERSITY, THE · PI LIAN, XIAOJUN · 2023 to 2024
$465k
NHLBI NIH HHS R01 HL175050NIDDK NIH HHS R01 DK112939NIDDK NIH HHS R56 DK133147
6 · The paper itself

Abstract

Embryos can achieve immune tolerance, yet the underlying mechanisms remain incompletely understood. Here, we demonstrate that pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), secrete extracellular vesicles (EVs) that markedly outperform mesenchymal stem cell (MSC)-derived EVs in suppressing pro-inflammatory cytokine secretion, inhibiting activated T-cell proliferation, and inducing regulatory T-cell (Treg) formation through CDK8 downregulation. Nuclear magnetic resonance (NMR) analysis reveals distinct molecular fingerprints of PSC EVs compared to those of MSC EVs. Moreover, comparative analyses show that PSC EVs contain unique proteins and microRNAs, such as the pluripotency-associated proteins ROR1 and CD133 and members of the miR-302 family, which are not found in MSC EVs, as determined by proteomic profiling and microRNA sequencing. Notably, the dynamic suspension culture of PSC aggregates significantly increases EV yield, offering a scalable and reproducible source superior to other cell sources. To evaluate their therapeutic potential, we employed an antigen-specific type 1 diabetes model and found that two local injections of iPSC EVs, particularly when delivered via a biomaterial scaffold, significantly enhanced diabetes-free survival. These treatments increased Treg populations in draining lymph nodes, induced systemic immunomodulation, and preserved β-cell mass from immune-mediated destruction. The immunomodulatory capability of PSC EVs suggests broad applications in treating autoimmune diseases and supporting stem cell-derived cell therapies by promoting immune tolerance. Their scalability, consistency, and superior therapeutic properties position PSC EVs as a compelling platform for next-generation immunotherapies and cell-based treatment strategies.

Identifiers

PMID40585231
PMCPMC12204458

What Socratic 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 Socratic graph.