Evidence mapPaperPMID 40682139Full record

ArticleStem cell research & therapy2025

hucMSC-derived exosomes targeting macrophage polarization attenuate systemic inflammation in T1DM via INS/SOD1 delivery.

Xin Chen, Hong An, Yongbiao Du, Hao Zhong, Fangfang Zhang, Xiaomei Zeng, Fen Lv, Zhihua Tian, Zaixue Jiang, Qi Peng and 5 more

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Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

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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

15 authors.

Xin ChenDepartment of Genetic Medicine, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China.
Hong AnKangchu Technology (Guangdong) Co., Ltd, Guangzhou, 510120, China.
Yongbiao DuKangchu Technology (Guangdong) Co., Ltd, Guangzhou, 510120, China.
Hao ZhongKangchu Technology (Guangdong) Co., Ltd, Guangzhou, 510120, China.
Fangfang ZhangDepartment of Genetic Medicine, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China.
Xiaomei ZengDepartment of Genetic Medicine, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China.
Fen LvDepartment of Genetic Medicine, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China.
Zhihua TianDepartment of Genetic Medicine, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China.
Zaixue JiangDepartment of Genetic Medicine, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China.
Qi PengDepartment of Genetic Medicine, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China.
Zengbao LiKangchu Technology (Guangdong) Co., Ltd, Guangzhou, 510120, China.
Siping LiDepartment of Genetic Medicine, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China.
Baimao ZhongDepartment of Genetic Medicine, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China. zbm@dgp-institute.com.
Xiaomei LuDepartment of Genetic Medicine, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China. lxm020@126.com.
Yinghua ZhuDepartment of Genetic Medicine, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China. zhuyinghua2003@163.com.ORCID http://orcid.org/0009-0008-3089-6510

Funding

Basic and Applied Basic Research Foundation of Guangdong Province 2023A1515140033Dongguan Eighth People's Hospital doctoral research start-up fund DBBS2023001National Natural Science Foundation of China 81872144
6 · The paper itself

Abstract

backgroundType 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by absolute insulin (INS) deficiency. As key components of the immune system, macrophages play critical roles in T1DM-associated pancreatic β-cell damage and multiorgan inflammatory injuries. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-EXOs) have emerged as promising therapeutic agents for immune-related disorders due to their immunomodulatory properties and favorable safety profile. However, systematic investigations into the therapeutic potential of hucMSC-EXOs in T1DM are lacking. This study aimed to evaluate the systemic anti-inflammatory effects of hucMSC-EXOs in T1DM and identify their key bioactive components.

methodsT1DM was induced in C57BL/6 male mice via streptozotocin, followed by intraperitoneal administration of hucMSC-EXOs. Systemic glucose metabolism, multiorgan pathology, and macrophage infiltration were assessed. In vitro, THP-1-derived macrophages were polarized to an M1 phenotype and treated with hucMSC-EXOs. Proteomic profiling, pharmacological inhibition, and functional assays were employed to identify critical exosomal components.

resultshucMSC-EXOs significantly reduced hyperglycemia, restored glucose tolerance, and attenuated structural damage in the pancreas, spleen, liver, kidney, and heart of T1DM mice (p < 0.05). Mechanistically, hucMSC-EXOs suppressed macrophage infiltration and proinflammatory cytokine secretion (IL-6, TNF-α, CCL-2) across tissues. Proteomic analysis revealed INS and superoxide dismutase 1 (SOD1) as enriched anti-inflammatory proteins in hucMSC-EXOs. Heat inactivation abolished their bioactivity, while pharmacological inhibition of INS (S961) or SOD1 (ATN-224) reversed hucMSC-EXOs-mediated suppression of macrophage activation (p < 0.01).

conclusionsThis study demonstrates that hucMSC-EXOs ameliorate T1DM- associated hyperglycemia and multiorgan inflammation by targeting macrophage polarization through delivery of INS and SOD1. Our study reveals that hucMSC-EXOs exert their anti-inflammatory effects through coordinated delivery of insulin and SOD1, establishing a protein-centric mechanism for exosome-mediated immunomodulation in T1DM.

Indexed as

Diabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1ExosomesInflammationInsulinMacrophagesMesenchymal Stem CellsSuperoxide Dismutase-1AnimalsHumansMaleMiceMice, Inbred C57BLUmbilical CordInsulinSuperoxide Dismutase-1ExosomesINSMacrophageSOD1Type 1 diabetes mellitus

Identifiers

PMID40682139
PMCPMC12275347

What Socratic holds

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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 Socratic graph.