Evidence map›Paper›PMID 41048938›Full record

ReviewFrontiers in medicine2025

Trends in mesenchymal stem cell-derived extracellular vesicles clinical trials 2014-2024: is efficacy optimal in a narrow dose range?

Yusong Wang, Junchi Zhu, Qimin Ma, Wei Zhou, Linshan Yang, Shuyue Sheng, Feng Zhu, Zhaofan Xia

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Frontiers in medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

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  11. Integrative Approaches to Treating Cellular Senescence in Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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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

8 authors.

Yusong Wang *Department of Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Junchi Zhu *Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qimin MaDepartment of Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Wei ZhouDepartment of Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Linshan YangDepartment of Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Shuyue ShengDepartment of Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Feng Zhu *Department of Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhaofan Xia *Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are emerging as promising cell-free therapeutic agents due to their immunomodulatory and regenerative properties. However, the lack of standardized protocols and dose optimization strategies has limited their clinical translation. While procedures for the isolation, expansion, and therapeutic use of mesenchymal stem cells (MSCs) have been standardized, there remains a lack of standardized protocols for the isolation and purification of EVs and exosomes (Exos). Methods: This review Comprehensive statistical summary global clinical trials involving MSC-EVs and Exos registered between 2014 and 2024, with a particular focus on dose-effect relationships and administration routes. Data were collected from ClinicalTrials.gov, the Chinese Clinical Trial Registry, and the Cochrane Register of Studies. A total of 66 eligible trials were included after screening. Results: Intravenous infusion and aerosolized inhalation were identified as the predominant administration methods, especially in trials targeting respiratory diseases. Notably, dose-effect results revealed that nebulization therapy achieved therapeutic effects at doses around 108 particles, significantly lower than those required for intravenous routes. This suggests a relatively narrow and route-dependent effective dose window. However, large variations in EVs characterization, dose units, and outcome measures were observed across trials, underscoring the lack of harmonized reporting standards. Conclusion: This review highlights dose-response as a critical but underappreciated gap in current MSC-EVs clinical research. The findings emphasize the urgent need for standardized dosing frameworks, potency assays, and harmonized clinical protocols to advance the safe and effective translation of MSC-EVs therapies. The analysis underscores the need for standardized protocols, global collaboration, and a deeper understanding of the biological mechanisms underlying MSC-EVs and Exos therapies to advance clinical applications and ensure safety and efficacy.

Indexed as

clinical trialsCOVID-19exosomesextracellular vesicleslung diseasesmesenchymal stem cellsnebulization

Identifiers

PMID41048938
PMCPMC12488731

What OpenQuestion holds

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LicenceCC BY
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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.