Exosomes Derived From Mesenchymal Stem Cells: Novel Effects in the Treatment of Ischemic Stroke

Overview

Journal Front Neurosci

Date 2022 May 19

PMID 35585925

Authors

Yu Xiong

Jianping Song

Xinyue Huang

Zhigang Pan

Roland Goldbrunner

Lampis Stavrinou

Shu Lin

Weipeng Hu

Feng Zheng

Pantelis Stavrinou

Affiliations

Soon will be listed here.

Abstract

Ischemic stroke is defined as an infarction in the brain, caused by impaired cerebral blood supply, leading to local brain tissue ischemia, hypoxic necrosis, and corresponding neurological deficits. At present, revascularization strategies in patients with acute ischemic stroke include intravenous thrombolysis and mechanical endovascular treatment. However, due to the short treatment time window (<4.5 h) and method restrictions, clinical research is focused on new methods to treat ischemic stroke. Exosomes are nano-sized biovesicles produced in the endosomal compartment of most eukaryotic cells, containing DNA, complex RNA, and protein (30-150 nm). They are released into surrounding extracellular fluid upon fusion between multivesicular bodies and the plasma membrane. Exosomes have the characteristics of low immunogenicity, good innate stability, high transmission efficiency, and the ability to cross the blood-brain barrier, making them potential therapeutic modalities for the treatment of ischemic stroke. The seed sequence of miRNA secreted by exosomes is base-paired with complementary mRNA to improve the microenvironment of ischemic tissue, thereby regulating downstream signal transduction activities. With exosome research still in the theoretical and experimental stages, this review aims to shed light on the potential of exosomes derived from mesenchymal stem cells in the treatment of ischemic stroke.

Citing Articles

Scalable production of anti-inflammatory exosomes from three-dimensional cultures of canine adipose-derived mesenchymal stem cells: production, stability, bioactivity, and safety assessment.

Thongsit A, Oontawee S, Siriarchavatana P, Rodprasert W, Somparn P, Na Nan D BMC Vet Res. 2025; 21(1):81.

PMID: 39979916 PMC: 11841348. DOI: 10.1186/s12917-025-04517-1.

Revolutionizing Neuroimmunology: Unraveling Immune Dynamics and Therapeutic Innovations in CNS Disorders.

Toader C, Tataru C, Munteanu O, Covache-Busuioc R, Serban M, Ciurea A Int J Mol Sci. 2025; 25(24.

PMID: 39769374 PMC: 11728275. DOI: 10.3390/ijms252413614.

Transplantation of Exosomes Derived From Human Wharton's Jelly Mesenchymal Stromal Cells Enhances Functional Improvement in Stroke Rats.

Chiu Y, Wu K, Yu S, Wu K, Hsieh C, Chou Y Cell Transplant. 2024; 33:9636897241296366.

PMID: 39624898 PMC: 11613244. DOI: 10.1177/09636897241296366.

Challenges in tendon-bone healing: emphasizing inflammatory modulation mechanisms and treatment.

Jiang F, Zhao H, Zhang P, Bi Y, Zhang H, Sun S Front Endocrinol (Lausanne). 2024; 15:1485876.

PMID: 39568806 PMC: 11576169. DOI: 10.3389/fendo.2024.1485876.

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

Xu K, Zhao X, He Y, Guo H, Zhang Y Front Pharmacol. 2024; 15:1481617.

PMID: 39508049 PMC: 11537945. DOI: 10.3389/fphar.2024.1481617.

References

Hou K, Li G, Zhao J, Xu B, Zhang Y, Yu J . Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway. J Neuroinflammation. 2020; 17(1):46. PMC: 6998092. DOI: 10.1186/s12974-020-1725-8. View

Salikhova D, Bukharova T, Cherkashova E, Namestnikova D, Leonov G, Nikitina M . Therapeutic Effects of hiPSC-Derived Glial and Neuronal Progenitor Cells-Conditioned Medium in Experimental Ischemic Stroke in Rats. Int J Mol Sci. 2021; 22(9). PMC: 8125106. DOI: 10.3390/ijms22094694. View

Chen W, Huang W, Yang Y, Li K . Methylglyoxal Scavengers Attenuate Angiogenesis Dysfunction Induced by Methylglyoxal and Oxygen-Glucose Deprivation. Oxid Med Cell Longev. 2022; 2022:8854457. PMC: 8754597. DOI: 10.1155/2022/8854457. View

Lou Y, Guo F, Liu F, Gao F, Zhang P, Niu X . miR-210 activates notch signaling pathway in angiogenesis induced by cerebral ischemia. Mol Cell Biochem. 2012; 370(1-2):45-51. DOI: 10.1007/s11010-012-1396-6. View

Kabekkodu S, Shukla V, Varghese V, D Souza J, Chakrabarty S, Satyamoorthy K . Clustered miRNAs and their role in biological functions and diseases. Biol Rev Camb Philos Soc. 2018; 93(4):1955-1986. DOI: 10.1111/brv.12428. View

Shi H, Tang H, Ai W, Zeng Q, Yang H, Zhu F . Schisandrin B Antagonizes Cardiotoxicity Induced by Pirarubicin by Inhibiting Mitochondrial Permeability Transition Pore (mPTP) Opening and Decreasing Cardiomyocyte Apoptosis. Front Pharmacol. 2021; 12:733805. PMC: 8554014. DOI: 10.3389/fphar.2021.733805. View

Fang H, Yang M, Pan Q, Jin H, Li H, Wang R . MicroRNA-22-3p alleviates spinal cord ischemia/reperfusion injury by modulating M2 macrophage polarization via IRF5. J Neurochem. 2020; 156(1):106-120. DOI: 10.1111/jnc.15042. View

Baruah J, Wary K . Exosomes in the Regulation of Vascular Endothelial Cell Regeneration. Front Cell Dev Biol. 2020; 7:353. PMC: 6962177. DOI: 10.3389/fcell.2019.00353. View

Hong S, Yang H, Manaenko A, Lu J, Mei Q, Hu Q . Potential of Exosomes for the Treatment of Stroke. Cell Transplant. 2018; 28(6):662-670. PMC: 6686440. DOI: 10.1177/0963689718816990. View

10.

Bsat S, Halaoui A, Kobeissy F, Moussalem C, El Houshiemy M, Kawtharani S . Acute ischemic stroke biomarkers: a new era with diagnostic promise?. Acute Med Surg. 2021; 8(1):e696. PMC: 8552525. DOI: 10.1002/ams2.696. View

11.

Rodriguez-Jimenez F, Vilches A, Perez-Arago M, Clemente E, Roman R, Leal J . Activation of Neurogenesis in Multipotent Stem Cells Cultured In Vitro and in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3. Neurotherapeutics. 2020; 18(1):515-533. PMC: 8116371. DOI: 10.1007/s13311-020-00928-0. View

12.

Eiro N, Fraile M, Fernandez-Francos S, Sanchez R, Costa L, Vizoso F . Importance of the origin of mesenchymal (stem) stromal cells in cancer biology: "alliance" or "war" in intercellular signals. Cell Biosci. 2021; 11(1):109. PMC: 8194017. DOI: 10.1186/s13578-021-00620-6. View

13.

Yan B, Zhang Y, Liang C, Liu B, Ding F, Wang Y . Stem cell-derived exosomes prevent pyroptosis and repair ischemic muscle injury through a novel exosome/circHIPK3/ FOXO3a pathway. Theranostics. 2020; 10(15):6728-6742. PMC: 7295049. DOI: 10.7150/thno.42259. View

14.

Wang Y, Zhang S, Li H, Wang H, Zhang T, Hutchinson M . Small-Molecule Modulators of Toll-like Receptors. Acc Chem Res. 2020; 53(5):1046-1055. DOI: 10.1021/acs.accounts.9b00631. View

15.

Xiao Y, Geng F, Wang G, Li X, Zhu J, Zhu W . Bone marrow-derived mesenchymal stem cells-derived exosomes prevent oligodendrocyte apoptosis through exosomal miR-134 by targeting caspase-8. J Cell Biochem. 2018; 120(2):2109-2118. DOI: 10.1002/jcb.27519. View

16.

Meng Z, Kang H, Duan W, Zheng J, Li Q, Zhou Z . MicroRNA-210 Promotes Accumulation of Neural Precursor Cells Around Ischemic Foci After Cerebral Ischemia by Regulating the SOCS1-STAT3-VEGF-C Pathway. J Am Heart Assoc. 2018; 7(5). PMC: 5866312. DOI: 10.1161/JAHA.116.005052. View

17.

Zhang Y, Hao Z, Wang P, Xia Y, Wu J, Xia D . Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1α-mediated promotion of angiogenesis in a rat model of stabilized fracture. Cell Prolif. 2019; 52(2):e12570. PMC: 6496165. DOI: 10.1111/cpr.12570. View

18.

Yang Y, Cai Y, Zhang Y, Liu J, Xu Z . Exosomes Secreted by Adipose-Derived Stem Cells Contribute to Angiogenesis of Brain Microvascular Endothelial Cells Following Oxygen-Glucose Deprivation In Vitro Through MicroRNA-181b/TRPM7 Axis. J Mol Neurosci. 2018; 65(1):74-83. DOI: 10.1007/s12031-018-1071-9. View

19.

Quaglia M, Merlotti G, Colombatto A, Bruno S, Stasi A, Franzin R . Stem Cell-Derived Extracellular Vesicles as Potential Therapeutic Approach for Acute Kidney Injury. Front Immunol. 2022; 13:849891. PMC: 8960117. DOI: 10.3389/fimmu.2022.849891. View

20.

Bruning E, Coller J, Wardill H, Bowen J . Site-specific contribution of Toll-like receptor 4 to intestinal homeostasis and inflammatory disease. J Cell Physiol. 2020; 236(2):877-888. DOI: 10.1002/jcp.29976. View