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Review
. 2024 Aug 12:18:1456775.
doi: 10.3389/fncel.2024.1456775. eCollection 2024.

Potential role of endothelial progenitor cells in the pathogenesis and treatment of cerebral aneurysm

Jin Yu #  1   2 , Qian Du #  3 , Xiang Li  2 , Wei Wei  2 , Yuncun Fan  4 , Jianjian Zhang  1   2 , Jincao Chen  1   2
Affiliations
Review

Potential role of endothelial progenitor cells in the pathogenesis and treatment of cerebral aneurysm

Jin Yu et al. Front Cell Neurosci. .

Abstract

Cerebral aneurysm (CA) is a significant health concern that results from pathological dilations of blood vessels in the brain and can lead to severe and potentially life-threatening conditions. While the pathogenesis of CA is complex, emerging studies suggest that endothelial progenitor cells (EPCs) play a crucial role. In this paper, we conducted a comprehensive literature review to investigate the potential role of EPCs in the pathogenesis and treatment of CA. Current research indicates that a decreased count and dysfunction of EPCs disrupt the balance between endothelial dysfunction and repair, thus increasing the risk of CA formation. Reversing these EPCs abnormalities may reduce the progression of vascular degeneration after aneurysm induction, indicating EPCs as a promising target for developing new therapeutic strategies to facilitate CA repair. This has motivated researchers to develop novel treatment options, including drug applications, endovascular-combined and tissue engineering therapies. Although preclinical studies have shown promising results, there is still a considerable way to go before clinical translation and eventual benefits for patients. Nonetheless, these findings offer hope for improving the treatment and management of this condition.

Keywords: cerebral aneurysm; endothelial dysfunction; endothelial progenitor cells; endothelialization; endovascular therapy.

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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
Abnormal count and dysfunction of endothelial progenitor cells (EPCs) in cerebral aneurysm (CA) condition. This diagram shows the rough process of obtaining EPCs from peripheral blood of CA patients and summarizes the abnormal cell counts and dysfunction of EPCs in CA condition reported in previous studies. The red arrow indicates “decreases” and the green arrow indicates “increase.”
FIGURE 2
FIGURE 2
Summary of pre-clinical EPC-based treatment researches for CA. Current studies primarily used rabbit or rat as animal models to simulate CA, aiming to verify the hypothesis that reversing the abnormalities of circulating EPCs in CA patients could repair the intima or stabilize aneurysms. By transfusing EPCs or factors stimulating EPCs mobilization, such as Stromal Cell-Derived Factor 1 alpha (SDF-1α) and Erythropoietin (EPO), into CA animal models to increase circulating EPCs, the progression of vascular degeneration after aneurysm induction was effectively reduced. ECFCs, endothelial colony-forming cells.
FIGURE 3
FIGURE 3
Conclusion in the effect of current and emerging treatments for CA on EPCs. Drugs stimulating EPCs mobilization: Statins (rosuvastatin, atorvastatin) and aspirin mobilize EPCs to aneurysm sites, enhancing endothelialization of aneurysm necks, reducing degeneration, and suppressing inflammation by inhibiting factors like iNOS, MMP-2, MMP-9, VEGF, NF-κB, MCP-1, and VCAM-1. These drugs also offer anti-inflammatory benefits, aiding aneurysm stabilization and rupture prevention; Endovascular surgery with EPCs agonists: EPCs activators enhance endothelialization over aneurysm areas after surgery. Combining EPCs stimulation with agonists (e.g., miR-31a-5p, EPO, rosuvastatin) improves treatment outcomes by reducing recanalization and enhancing safety and effectiveness; Flow diverter implants and EPCs-based tissue engineering: Flow diverter implants facilitate vessel reconstruction and aneurysm thrombosis, with EPCs supporting endothelialization. EPC-based tissue engineering uses biopolymer- combined EPCs injected into aneurysms, resulting in a stable endothelial layer and neointima formation.
See this image and copyright information in PMC

References

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Grants and funding

The authors declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Hubei Provincial Natural Science Foundation of China (2024AFB308), The Outstanding Postdoctoral Research Fund of Zhongnan Hospital, Wuhan University (ZNYB2021002), and The Science and Technology Innovation Cultivation Fund of Zhongnan Hospital, Wuhan University (CXPY2022027).

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