Exosomes Interactions with the Blood–Brain Barrier: Implications for Cerebral Disorders and Therapeutics
Abstract
:1. Introduction
2. Exosomes Biogenesis
2.1. Exosomes Biogenesis
2.2. Exosomal Content
3. Transport of Exosomes through the Blood–Brain Barrier
4. Physiological Regulation of the Blood–Brain Barrier by Exosomes
5. Regulation of the Blood–Brain Barrier by Exosomes in Brain Diseases
5.1. Brain Glioma
5.2. Metastatic Brain Tumors
5.2.1. Metastatic Breast Cancer
5.2.2. Metastatic Lung Cancer
5.2.3. Other Types of Metastatic Cancer
5.3. Traumatic Brain Injury
5.4. Stroke
5.5. Neuroinflammation
5.6. Neurodegenerative Diseases
6. Conclusions and Prospects
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Transport Pathway | Mode of Transport | Energy Requirement | Reference |
---|---|---|---|
Fusion with the plasma membrane | Movement is achieved through physical interaction between the exosome and the cell plasma membrane | Low | [48] |
Paracytosis | Movement of exosomes between the BMEC | Low | [43] |
Transcytosis | Movement of exosomes across the BMEC | High | [45,46] |
Micropinocytosis | The inward curvature of the cellular membrane and engulfment of exosomes | High | [43] |
Type of Metastatic Cancer | Exosomal Content | Effect on the BBB | In-Vivo/In-Vitro | Reference |
---|---|---|---|---|
Breast cancer | miR-105 | Reduce the expression of TJs at BMEC | in-vitro and in-vivo | [69] |
Breast cancer | miR-181c | Change the localization of TJs and actin filaments by inducing downregulation of PDPK1 gene in BMEC | in-vivo and in-vitro | [12] |
Breast cancer | lncRNA GS1-600G8.5 | Reduce the expression of TJs at BMEC | in-vitro | [115] |
Breast cancer | CEMIP | Increase the vascular co-option | in-vitro | [117] |
Induce proinflammatory phenotype in BMEC | in-vivo | |||
Lung cancer | miR-550a-3-5p | Reduce expression of Yes-associated protein 1 in BMEC | in-vitro | [16] |
Lung cancer | LINC01356 | Reduce expression of TJs at BMEC | in-vitro | [122] |
Lung cancer | Lnc-MMP2-2 | Upregulate EPB41L5 that induces endothelial-to-Mesenchymal Transition and causes a reciprocal repression of BMECs TJs | in-vitro and in-vivo | [123] |
Condition | Trial Description | Interventions | Phase | Study Status | Enrollment | NCT Number |
---|---|---|---|---|---|---|
Cerebrovascular Disorders | Using MSC exosomes to improve functional recovery in poststroke patients. | MSC exosomes | Phase 1, Phase 2 | Unknown | N = 5 | NCT03384433 |
Refractory Focal Epilepsy | Assess the safety, efficacy, and tolerability of nasal drops containing induced pluripotent stem cell (IPSC) exosomes in focal refractory epilepsy therapy. | IPSC exosomes | Early Phase 1 | Recruiting | N = 34 | NCT05886205 |
Post-stroke Dementia | Investigating the significance of acupuncture-induced exosomes in post-stroke dementia therapy. | Device: Acupuncture | Not applicable | Recruiting | N = 30 | NCT05326724 |
Alzheimer Disease | Assessing the efficacy and safety of allogenic adipose mesenchymal stem cell exosomes in AD patients with dementia. | low, mild, and high dosage MSC Exosomes administrated for nasal drip | Phase 1, Phase 2 | Unknown Status | N = 9 | NCT04388982 |
Malignant Glioma of Brain | Activating the patient’s immune system using apoptosis released tumor exosomes loaded with tumor antigens. | Drug: IGF-1R/AS ODN | Phase 1 | Completed | N = 13 | NCT01550523 |
Device: biodiffusion chamber |
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Osaid, Z.; Haider, M.; Hamoudi, R.; Harati, R. Exosomes Interactions with the Blood–Brain Barrier: Implications for Cerebral Disorders and Therapeutics. Int. J. Mol. Sci. 2023, 24, 15635. https://doi.org/10.3390/ijms242115635
Osaid Z, Haider M, Hamoudi R, Harati R. Exosomes Interactions with the Blood–Brain Barrier: Implications for Cerebral Disorders and Therapeutics. International Journal of Molecular Sciences. 2023; 24(21):15635. https://doi.org/10.3390/ijms242115635
Chicago/Turabian StyleOsaid, Zaynab, Mohamed Haider, Rifat Hamoudi, and Rania Harati. 2023. "Exosomes Interactions with the Blood–Brain Barrier: Implications for Cerebral Disorders and Therapeutics" International Journal of Molecular Sciences 24, no. 21: 15635. https://doi.org/10.3390/ijms242115635
APA StyleOsaid, Z., Haider, M., Hamoudi, R., & Harati, R. (2023). Exosomes Interactions with the Blood–Brain Barrier: Implications for Cerebral Disorders and Therapeutics. International Journal of Molecular Sciences, 24(21), 15635. https://doi.org/10.3390/ijms242115635