Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct 23:15:1481617.
doi: 10.3389/fphar.2024.1481617. eCollection 2024.

Stem cell-derived exosomes for ischemic stroke: a conventional and network meta-analysis based on animal models

Kangli Xu  1   2 , Xiaohui Zhao  1   2 , Yuxuan He  1   2 , Hongxin Guo  1   2 , Yunke Zhang  1
Affiliations

Stem cell-derived exosomes for ischemic stroke: a conventional and network meta-analysis based on animal models

Kangli Xu et al. Front Pharmacol. .

Abstract

Objective: We aimed to evaluate the efficacy of stem cell-derived exosomes for treating ischemic stroke and to screen for the optimal administration strategy.

Methods: We searched PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases for relevant studies published from their inception to 31 December 2023. Conventional and network meta-analyses of the routes of administration, types, and immune compatibility of stem cell-derived exosomes were performed using the cerebral infarct volume (%) and modified neurological severity score (mNSS) as outcome indicators.

Results: A total of 38 randomized controlled animal experiments were included. Conventional meta-analysis showed that compared with the negative control group: intravenous administration significantly reduced the cerebral infarct volume (%) and mNSS; intranasal administration significantly reduced the cerebral infarct volume (%); and intracerebral administration significantly reduced the mNSS. Adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos), bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos), dental pulp stem cell-derived exosomes (DPSC-Exos) and neural stem cell-derived exosomes (NSC-Exos) significantly reduced the cerebral infarct volume (%) and mNSS; Endothelial progenitor cell-derived exosomes (EPC-Exos), embryonic stem cell-derived exosomes (ESC-Exos), induced pluripotent stem cell-derived exosomes (iPSC-Exos) and neural progenitor cell-derived exosomes (NPC-Exos) significantly reduced the cerebral infarct volume (%); Umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) significantly reduced the mNSS; and there was no significant difference between urogenital stem cell-derived exosomes (USC-Exos) and negative controls. Engineered modified exosomes had better efficacy than unmodified exosomes. Both allogeneic and xenogeneic stem cell-derived exosomes significantly reduced the cerebral infarct volume (%) and the mNSS. The network meta-analysis showed that intravenous administration was the best route of administration for reducing the cerebral infarct volume (%) and mNSS. Among the 10 types of stem cell-derived exosomes that were administered intravenously, BMSC-Exos were the best type for reducing the cerebral infarct volume (%) and the mNSS. Allogeneic exosomes had the best efficacy in reducing the cerebral infarct volume (%), whereas xenogeneic stem cell-derived exosomes had the best efficacy in reducing the mNSS.

Conclusion: This meta-analysis, by integrating the available evidence, revealed that intravenous administration is the best route of administration, that BMSC-Exos are the best exosome type, that allogeneic exosomes have the best efficacy in reducing the cerebral infarct volume (%), and that xenogeneic exosomes have the best efficacy in reducing mNSS, which can provide options for preclinical studies. In the future, more high-quality randomized controlled animal experiments, especially direct comparative evidence, are needed to determine the optimal administration strategy for stem cell-derived exosomes for ischemic stroke.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42024497333, PROSPERO, CRD42024497333.

Keywords: animal experiments; animal models; exosomes; meta-analysis; stem cells; stroke.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of the literature selection process.
FIGURE 2
FIGURE 2
Exosome characterization and risk of bias for publications. (A) Types of stem cell-derived exosomes; (B) routes of administration of stem cell-derived exosomes; (C) risk of bias of the included studies; (D) summarized risk of bias of the included studies.
FIGURE 3
FIGURE 3
Forest plot for conventional meta-analysis of the effects of routes of administration on the cerebral infarct volume (%).
FIGURE 4
FIGURE 4
Forest plot for conventional meta-analysis of the effect of stem cell-derived exosomes on cerebral infarct volume (%).
FIGURE 5
FIGURE 5
Forest plot for conventional meta-analysis of the effect of immune compatibility on the cerebral infarct volume (%).
FIGURE 6
FIGURE 6
Network evidence maps of the cerebral infarct volume (%). (A) Routes of administration; (B) Stem cell-derived exosome types; (C) Immune compatibility.
FIGURE 7
FIGURE 7
Rank probability ranking plots for the cerebral infarct volume (%). (A) Routes of administration; (B) Stem cell-derived exosome types; (C) Immune compatibility; Rank 1 is the worst, and rank N is the best.
FIGURE 8
FIGURE 8
Forest plot for conventional meta-analysis of the effects of routes of administration on the mNSS.
FIGURE 9
FIGURE 9
Forest plot for conventional meta-analysis of the effects of stem cell-derived exosomes on the mNSS.
FIGURE 10
FIGURE 10
Forest plot for conventional meta-analysis of immune compatibility on the mNSS.
FIGURE 11
FIGURE 11
Network evidence maps for the mNSS. (A) Routes of administration; (B) Stem cell-derived exosome types; (C) Immune compatibility.
FIGURE 12
FIGURE 12
Rank probability ranking plots for the mNSS. (A) Routes of administration; (B) Stem cell-derived exosome types; (C) Immune compatibility; Rank 1 is the worst, and rank N is the best.
FIGURE 13
FIGURE 13
Funnel plots of the included studies. (A) Studies reporting the cerebral infarct volume (%); (B) Studies reporting the mNSS.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abdulmalek O. A. A. Y., Husain K. H., AlKhalifa H. K. A. A., Alturani M. M. A. B., Butler A. E., Moin A. S. M. (2024). Therapeutic applications of stem cell-derived exosomes. Int. J. Mol. Sci. 25, 3562. 10.3390/ijms25063562 - DOI - PMC - PubMed
    1. Asgari Taei A., Khodabakhsh P., Nasoohi S., Farahmandfar M., Dargahi L. (2022). Paracrine effects of mesenchymal stem cells in ischemic stroke: opportunities and challenges. Mol. Neurobiol. 59, 6281–6306. 10.1007/s12035-022-02967-4 - DOI - PubMed
    1. Betzer O., Perets N., Angel A., Motiei M., Sadan T., Yadid G., et al. (2017). In vivo neuroimaging of exosomes using gold nanoparticles. ACS Nano 11, 10883–10893. 10.1021/acsnano.7b04495 - DOI - PubMed
    1. Cai Y., Liu W., Lian L., Xu Y., Bai X., Xu S., et al. (2020). Stroke treatment: is exosome therapy superior to stem cell therapy? Biochimie 179, 190–204. 10.1016/j.biochi.2020.09.025 - DOI - PubMed
    1. Campero-Romero A. N., Real F. H., Santana-Martínez R. A., Molina-Villa T., Aranda C., Ríos-Castro E., et al. (2023). Extracellular vesicles from neural progenitor cells promote functional recovery after stroke in mice with pharmacological inhibition of neurogenesis. Cell. Death Discov. 9, 272. 10.1038/s41420-023-01561-4 - DOI - PMC - PubMed

Publication types

LinkOut - more resources