Evidence map›Paper›PMID 34627385›Full record

ArticleStem cell research & therapy2021

SPION-MSCs enhance therapeutic efficacy in sepsis by regulating MSC-expressed TRAF1-dependent macrophage polarization.

Yujun Xu, Xinghan Liu, Yi Li, Huan Dou, Huaping Liang, Yayi Hou

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 20% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Effect of clinically relevant iron oxide nanoparticles on macrophage polarization, tumor growth and tumor microenvironment modulation.Journal of controlled release : official journal of the Controlled Release Society · 2026
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  12. The Role of Histone Deacetylases in Acute Lung Injury-Friend or Foe.International journal of molecular sciences · 2023
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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

6 authors at 2 institutions in 1 country.

Yujun XuThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, 22 Hankou Road, Nanjing, 210093, China.
Xinghan LiuThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, 22 Hankou Road, Nanjing, 210093, China.
Yi LiThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, 22 Hankou Road, Nanjing, 210093, China.
Huan DouThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, 22 Hankou Road, Nanjing, 210093, China.
Huaping LiangState Key Laboratory of Trauma, Burns and Combined Injury, Department of Wound Infection and Drug, Daping Hospital, Army Medical University, Chongqing, China. 13638356728@163.com.
Yayi HouThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, 22 Hankou Road, Nanjing, 210093, China. yayihou@nju.edu.cn.
Nanjing University · CNDaping Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The liver has a crucial role in sepsis and is also a target for sepsis-related injury. Macrophage polarization between the M1 and M2 types is involved in the progression and resolution of both inflammation and liver injury. Iron oxide-based synthetic nanoparticles (SPIONs) can be used as antibacterial agents to regulate the inflammatory response. Mesenchymal stromal/stem cells (MSCs) have been widely used in the treatment of autoimmune diseases, sepsis, and other diseases. However, to date, both the effects of SPIONs on MSCs and the fate of SPION-labelled MSCs in sepsis and other diseases are still unclear.

methodsMice were subjected to caecal ligation and puncture (CLP) or lipopolysaccharide (LPS) induction to develop sepsis models. The CLP or LPS models were treated with MSCs or SPION-labelled/pretreated MSCs (SPION-MSCs). Bone marrow (BM)-derived macrophages and RAW 264.7 cells were cocultured with MSCs or SPION-MSCs under different conditions. Flow cytometry, transmission electron microscopy, western blotting, quantitative real-time PCR, and immunohistochemical analysis were performed.

resultsWe found that SPIONs did not affect the basic characteristics of MSCs. SPIONs promoted the survival of MSCs by upregulating HO-1 expression under inflammatory conditions. SPION-MSCs enhanced the therapeutic efficacy of liver injury in both the CLP- and LPS-induced mouse models of sepsis. Moreover, the protective effect of SPION-MSCs against sepsis-induced liver injury was related to macrophages. Systemic depletion of macrophages reduced the efficacy of SPION-MSC therapy. Furthermore, SPION-MSCs promoted macrophages to polarize towards the M2 phenotype under sepsis-induced liver injury in mice. The enhanced polarization towards M2 macrophages was attributed to their phagocytosis of SPION-MSCs. SPION-MSC-expressed TRAF1 was critical for promotion of macrophage polarization and alleviation of sepsis in mice.

conclusionMSCs labelled/pretreated with SPIONs may be a novel therapeutic strategy to prevent or treat sepsis and sepsis-induced liver injury. HIGHLIGHTS: 1. SPIONs enhance the viability of MSCs by promoting HO-1 expression. 2. SPION-labelled/pretreated MSCs effectively improve sepsis by regulating macrophage polarization to M2 macrophages. 3. SPION-labelled/pretreated MSCs regulate macrophage polarization in a manner dependent on MSC-expressed TRAF1 protein.

Indexed as

Macrophage ActivationSepsisAnimalsMacrophagesMagnetic Iron Oxide NanoparticlesMiceTNF Receptor-Associated Factor 1TNF Receptor-Associated Factor 1MacrophagesMSCsSepsisSPIONs

Identifiers

PMID34627385
PMCPMC8501658
OpenAlexW3207430121

What OpenQuestion 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 OpenQuestion graph.