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Review
. 2025 Apr 7:19:1536028.
doi: 10.3389/fncel.2025.1536028. eCollection 2025.

Blood-brain barrier repair: potential and challenges of stem cells and exosomes in stroke treatment

Xiaochen Fu  1   2 , Jia Li  1   2 , Shoujun Yang  1 , Jiapeng Jing  1   2 , Qinzhi Zheng  1   2 , Ting Zhang  1   2 , Zhuo Xu  1
Affiliations
Review

Blood-brain barrier repair: potential and challenges of stem cells and exosomes in stroke treatment

Xiaochen Fu et al. Front Cell Neurosci. .

Abstract

Stroke is characterized with high morbidity, mortality and disability all over the world, and one of its core pathologies is blood-brain barrier (BBB) dysfunction. BBB plays a crucial physiological role in protecting brain tissues and maintaining homeostasis in central nervous system (CNS). BBB dysfunction serves as a key factor in the development of cerebral edema, inflammation, and further neurological damage in stroke patients. Currently, stem cells and their derived exosomes have shown remarkable potential in repairing the damaged BBB and improving neurological function after stroke. Stem cells repair the integrity of BBB through anti-inflammatory, antioxidant, angiogenesis and regulation of intercellular signaling mechanisms, while stem cell-derived exosomes, as natural nanocarriers, further enhance the therapeutic effect by carrying active substances such as proteins, RNAs and miRNAs. This review will present the latest research advances in stem cells and their exosomes in stroke treatment, as well as the challenges of cell source, transplantation timing, dosage, and route of administration in clinical application, aiming to discuss their mechanisms of repairing BBB integrity and potential for clinical application, and proposes future research directions. Stem cells and exosomes are expected to provide new strategies for early diagnosis and precise treatment of stroke, and promote breakthroughs in the field of stroke.

Keywords: blood brain barrier; cell therapy; exosomes; stem cell; stroke.

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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
Models, pathophysiology and the role of complement system of stroke (by Figdraw).
FIGURE 2
FIGURE 2
The primary mechanisms of post-stroke blood-brain barrier (BBB) impairment can be categorized as follows: (A) Inflammatory response: leukocyte infiltration and microglia activation after stroke release inflammatory mediators that damage the endothelial cells and tight junctions of the BBB and increase its permeability. (B) Oxidative stress: stroke leads to impaired energy metabolism in the brain, elevated reactive oxygen species (ROS) production, and impaired antioxidant defense system. ROS attack the components of the BBB, destroying its structure and function. (C) Cytokine release: after stroke, cytokines such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are released, the former activating relevant receptors to open tight junctions, and the latter degrading extracellular matrix and tight junction proteins to disrupt the integrity of the BBB. (D) Apoptosis: stroke-induced factors induce apoptosis or abnormal function of blood-brain barrier endothelial cells and astrocytes, leading to structural disintegration and destabilization of the BBB (by Figdraw).
FIGURE 3
FIGURE 3
Nature markers, advantages and disadvantages of stem cells (by Figdraw).
FIGURE 4
FIGURE 4
Physical characteristics, various markers and isolation strategies of exosomes (by Figdraw).
FIGURE 5
FIGURE 5
Exosomes in the diagnosis and treatment of BBB damage after stroke (by Figdraw).
FIGURE 6
FIGURE 6
Strategies for reprogramming of glial cells into functional neurons (by Figdraw).
See this image and copyright information in PMC

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