Extracellular Vesicles (EVs) as “A Window to the Brain”: Potential, Challenges and Future Perspectives

Mitra, Prasenjit; Gupta, Shruti; Sharma, Praveen

doi:10.1007/s12291-023-01111-w

Cited by 5 publications

(2 citation statements)

References 15 publications

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“…However, it must be considered that despite the enriched presence of different types of EVs in biological fluids, these particles represent a mixed fraction of vesicles produced by different cell types, and the therapeutic effect depends on the donor [ 113 ], which complicates the standardization of drugs for clinical use. Also, EVs isolated from these fluids may reflect the homeostasis of the corresponding tissues and organs and potentially serve as markers for various pathological conditions [ 114 , 115 , 116 , 117 ].…”

Section: Sources Of Evs and Methods For Their Isolationmentioning

confidence: 99%

A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic

Goryunov,

Ivanov,

Kulikov

et al. 2024

IJMS

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Neonatal disorders, particularly those resulting from prematurity, pose a major challenge in health care and have a significant impact on infant mortality and long-term child health. The limitations of current therapeutic strategies emphasize the need for innovative treatments. New cell-free technologies utilizing extracellular vesicles (EVs) offer a compelling opportunity for neonatal therapy by harnessing the inherent regenerative capabilities of EVs. These nanoscale particles, secreted by a variety of organisms including animals, bacteria, fungi and plants, contain a repertoire of bioactive molecules with therapeutic potential. This review aims to provide a comprehensive assessment of the therapeutic effects of EVs and mechanistic insights into EVs from stem cells, biological fluids and non-animal sources, with a focus on common neonatal conditions such as hypoxic–ischemic encephalopathy, respiratory distress syndrome, bronchopulmonary dysplasia and necrotizing enterocolitis. This review summarizes evidence for the therapeutic potential of EVs, analyzes evidence of their mechanisms of action and discusses the challenges associated with the implementation of EV-based therapies in neonatal clinical practice.

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Section: Sources Of Evs and Methods For Their Isolationmentioning

confidence: 99%

A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic

Goryunov,

Ivanov,

Kulikov

et al. 2024

IJMS

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“…EVs are membrane-bound structures secreted by all cell types and found in all body fluids as well as in conditioned media from cell cultures ( 18 ). Since EVs reflect the state of their cell-of-origin, they can serve as a rich source of information that can be leveraged for understanding molecular mechanisms at play in vivo in an inaccessible organ, such as the brain ( 19 , 20 ). With this in-depth characterization of JCPyV-infected astrocytes and secreted vesicles, we move closer to defining the role of astrocytes in JCPyV propagation and open new avenues toward the development of antiviral strategies for patients with PML.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive proteomic analysis of JC polyomavirus-infected human astrocytes and their extracellular vesicles

Oberholster,

Mathias,

Perriot

et al. 2023

Microbiol Spectr

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JC polyomavirus (JCPyV) is an opportunistic virus that remains in a latent state in the kidneys and lymphoid organs of more than half of the human adult population. In rare cases of severe immune suppression, the virus is able to establish a lytic infection of glial cells in the brain, resulting in a debilitating, demyelinating disease known as progressive multifocal leukoencephalopathy (PML). Because of the exceptional species and tissue specificity of the virus, appropriate models of JCPyV infection in the brain are lacking, thus hampering progress toward the development of novel antiviral strategies and biomarkers of disease activity. While PML has traditionally been characterized as a lytic infection of oligodendrocytes, more recent findings suggest an important role for astrocytes during the initial stages of disease. Here, using human-induced pluripotent stem cell (hiPSC)-derived astrocytes coupled with a multiparametric approach, we show that (i) JCPyV readily infects and replicates in astrocytes, (ii) JCPyV strongly dysregulates the cell biology, and (iii) these results adequately reflect ex vivo findings. We perform an in-depth characterization of the effect of JCPyV on the cell proteome over time, demonstrating a strong dysregulation of the cell cycle and activation of the DNA damage response. Furthermore, we show that the proteomic signature observed for infected astrocytes is extended to extracellular vesicles, underlining their potential as a resource to gain valuable insights into JCPyV infection in the brain. IMPORTANCE Progressive multifocal leukoencephalopathy is a crimpling demyelinating disease of the central nervous system caused by JC polyomavirus (JCPyV). Much about JCPyV propagation in the brain remains obscure because of a lack of proper animal models to study the virus in the context of the disease, thus hampering efforts toward the development of new antiviral strategies. Here, having established a robust and representative model of JCPyV infection in human-induced pluripotent stem cell-derived astrocytes, we are able to fully characterize the effect of JCPyV on the biology of the cells and show that the proteomic signature observed for JCPyV-infected astrocytes is extended to extracellular vesicles (EVs). These data suggest that astrocyte-derived EVs found in body fluids might serve as a rich source of information relevant to JCPyV infection in the brain, opening avenues toward better understanding the pathogenesis of the virus and, ultimately, the identification of new antiviral targets.

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Overcoming biological barriers: Precision engineered extracellular vesicles for personalized neuromedicine

Ravichandiran,

Kesharwani,

Anupriya

et al. 2024

Precision Medicine and Engineering

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Extracellular Vesicles (EVs) as “A Window to the Brain”: Potential, Challenges and Future Perspectives

Cited by 5 publications

References 15 publications

A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic

A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic

Comprehensive proteomic analysis of JC polyomavirus-infected human astrocytes and their extracellular vesicles

Overcoming biological barriers: Precision engineered extracellular vesicles for personalized neuromedicine

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