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Peer-reviewedCC BY-NC-ND 4.0International Journal of Molecular Medicine

Multiple strategies to improve the therapeutic efficacy of mesenchymal stem cell-derived exosome transplantation in ischemic stroke (Review)

  • Yan Xu1,2,3
  • Xiaolei Zhou1,2
  • Wenhui Zeng1,2
  • Jiabing Wang1,4
  • Lin Zhou1,5,6,7
  • Lincai Li1,5,6,7
  • Zhengwei Zou1,5,6,7
  • Cixiang Chen8
  • Yichi Zhang8
  • Zhengyi He9
  • Junsong Ye1,5,6,7,10
10 affiliations
  1. 1Center for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
  2. 2School of Rehabilitation and Exercise Health, Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
  3. 3Department of Rehabilitation Medicine, Siyang Hospital, Suqian, Jiangsu 223700, P.R. China
  4. 4School of Pharmacy, Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
  5. 5Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou, Jiangxi 341000, P.R. China
  6. 6Jiangxi Provincial Key Laboratory of Tissue Engineering, Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
  7. 7Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
  8. 8First Clinical College, Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
  9. 9Department of Clinical Medicine Research Center, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
  10. 10JXHC Key Laboratory of Stem Cells and Emerging Biotechnology, Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
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Abstract

Ischemic stroke (IS) is a common cause of physical disability and death worldwide. Although it has been indicated that mesenchymal stem cells (MSCs) can treat IS through mechanisms such as immunomodulation, angiogenesis and neuroprotection, their clinical application is limited by inherent drawbacks, such as immune rejection risk and tumorigenic potential. Notably, MSC-derived exosomes (MSC-Exos) possess advantages, such as a smaller volume, low immunogenicity and low tumorigenicity, enabling therapeutic effects similar to those of the parent cells. Furthermore, MSC-Exos can carry various bioactive substances and cross the blood-brain barrier (BBB), thus indicating their potential in the diagnosis, treatment and prognostic assessment of IS. The present review comprehensively elaborates on the principles by which MSC-Exos may treat IS through mechanisms such as inhibiting inflammatory responses, suppressing apoptosis, promoting angiogenesis, regulating ferroptosis and maintaining BBB integrity. However, the therapeutic efficacy of MSC-Exo monotherapy is restricted by its low brain bioavailability, short lesion retention time, insufficient in vivo stability and inability to remain at the lesion site for an extended period of time to exert its effect. Furthermore, the review summarizes the recent optimization strategies involving the combination of MSC-Exos with microRNAs, traditional Chinese medicine, hydrogels, exosome pretreatment and electroacupuncture to enhance the efficacy of MSC-Exo therapy for IS, and systematically reviews their synergistic therapeutic mechanisms. In addition, the current status of clinical translation, technical breakthrough obstacles and future development directions for MSC-Exo combination therapies in neurological diseases is outlined, providing a theoretical reference for innovative treatments of IS.

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Cite

BibTeXRIS
BibTeX
@article{xu2026multiple,
  title = {{Multiple strategies to improve the therapeutic efficacy of mesenchymal stem cell-derived exosome transplantation in ischemic stroke (Review)}},
  author = {Yan Xu and Xiaolei Zhou and Wenhui Zeng and Jiabing Wang and Lin Zhou and Lincai Li and Zhengwei Zou and Cixiang Chen and Yichi Zhang and Zhengyi He and Junsong Ye},
  journal = {International Journal of Molecular Medicine},
  year = {2026},
  month = oct,
  doi = {10.3892/ijmm.2026.6016},
  url = {https://doi.org/10.3892/ijmm.2026.6016},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Multiple strategies to improve the therapeutic efficacy of mesenchymal stem cell-derived exosome transplantation in ischemic stroke (Review)
AU  - Yan Xu
AU  - Xiaolei Zhou
AU  - Wenhui Zeng
AU  - Jiabing Wang
AU  - Lin Zhou
AU  - Lincai Li
AU  - Zhengwei Zou
AU  - Cixiang Chen
AU  - Yichi Zhang
AU  - Zhengyi He
AU  - Junsong Ye
PY  - 2026
DA  - 2026/10/14
JO  - International Journal of Molecular Medicine
DO  - 10.3892/ijmm.2026.6016
UR  - https://doi.org/10.3892/ijmm.2026.6016
AB  - Ischemic stroke (IS) is a common cause of physical disability and death worldwide. Although it has been indicated that mesenchymal stem cells (MSCs) can treat IS through mechanisms such as immunomodulation, angiogenesis and neuroprotection, their clinical application is limited by inherent drawbacks, such as immune rejection risk and tumorigenic potential. Notably, MSC-derived exosomes (MSC-Exos) possess advantages, such as a smaller volume, low immunogenicity and low tumorigenicity, enabling therapeutic effects similar to those of the parent cells. Furthermore, MSC-Exos can carry various bioactive substances and cross the blood-brain barrier (BBB), thus indicating their potential in the diagnosis, treatment and prognostic assessment of IS. The present review comprehensively elaborates on the principles by which MSC-Exos may treat IS through mechanisms such as inhibiting inflammatory responses, suppressing apoptosis, promoting angiogenesis, regulating ferroptosis and maintaining BBB integrity. However, the therapeutic efficacy of MSC-Exo monotherapy is restricted by its low brain bioavailability, short lesion retention time, insufficient in vivo stability and inability to remain at the lesion site for an extended period of time to exert its effect. Furthermore, the review summarizes the recent optimization strategies involving the combination of MSC-Exos with microRNAs, traditional Chinese medicine, hydrogels, exosome pretreatment and electroacupuncture to enhance the efficacy of MSC-Exo therapy for IS, and systematically reviews their synergistic therapeutic mechanisms. In addition, the current status of clinical translation, technical breakthrough obstacles and future development directions for MSC-Exo combination therapies in neurological diseases is outlined, providing a theoretical reference for innovative treatments of IS.
SN  - 1107-3756
SN  - 1791-244X
ER  -