Engineered extracellular vesicles encapsulated Bryostatin-1 as therapy for neuroinflammation

Wu, Wei; Tian, Jing; Xiao, Dan; Guo, Yuxin; Xiao, Yun; Wu, Xiaoyu; Casella, Giacomo; Rasouli, Javad; Yan, Yaping; Rostami, Abdolmohamad; Wang, Libin; Zhang, Yuan; Li, Xing

doi:10.1039/d1nr05517h

Cited by 17 publications

(12 citation statements)

References 49 publications

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“…Recent reports have highlighted the neuroprotective impact of EVs derived from other systems as therapy for MS. Engineered neural stem cell-derived EVs loaded with Bryostatin-1 (Bryo-1), a marine lactone, targeted neuroinflammation and facilitated remyelination in the MS brain. Interestingly, the effect was observed at low doses of Bryo-2 (1 × 10 8 particles) when encapsulated in the EVs compared to the systemic delivery of Bryo-1 alone .…”

Section: Role Of Evs In Brain Disorders: Involvement In Pathogenesis ...mentioning

confidence: 99%

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications

Onkar,

Khan,

Goenka

et al. 2024

ACS Appl. Mater. Interfaces

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Information exchange is essential for the brain, where it communicates the physiological and pathological signals to the periphery and vice versa. Extracellular vesicles (EVs) are a heterogeneous group of membrane-bound cellular informants actively transferring informative calls to and from the brain via lipids, proteins, and nucleic acid cargos. In recent years, EVs have also been widely used to understand brain function, given their "cell-like" properties. On the one hand, the presence of neuron and astrocyte-derived EVs in biological fluids have been exploited as biomarkers to understand the mechanisms and progression of multiple neurological disorders; on the other, EVs have been used in designing targeted therapies due to their potential to cross the blood-brain-barrier (BBB). Despite the expanding literature on EVs in the context of central nervous system (CNS) physiology and related disorders, a comprehensive compilation of the existing knowledge still needs to be made available. In the current review, we provide a detailed insight into the multifaceted role of brain-derived extracellular vesicles (BDEVs) in the intricate regulation of brain physiology. Our focus extends to the significance of these EVs in a spectrum of disorders, including brain tumors, neurodegenerative conditions, neuropsychiatric diseases, autoimmune disorders, and others. Throughout the review, parallels are drawn for using EVs as biomarkers for various disorders, evaluating their utility in early detection and monitoring. Additionally, we discuss the promising prospects of utilizing EVs in targeted therapy while acknowledging the existing limitations and challenges associated with their applications in clinical scenarios. A foundational comprehension of the current state-of-the-art in EV research is essential for informing the design of future studies.

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Section: Role Of Evs In Brain Disorders: Involvement In Pathogenesis ...mentioning

confidence: 99%

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications

Onkar,

Khan,

Goenka

et al. 2024

ACS Appl. Mater. Interfaces

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“…[20] Also, EVs display innate properties, such as the ability to cross biological barriers (e.g., blood brain barrier, although the mechanisms are not fully elucidated), [26,27] and a potential low immunogenicity. [28,29] Moreover, EVs possess a fingerprint, inherited from their donor cells, that distinguishes vesicles derived from different cell types. [20,[30][31][32] Importantly, the EV content: i) reflects the "status" of the donor cell; and ii) it can change in response to specific modifications in the microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Small Extracellular Vesicles Secreted by Nigrostriatal Astrocytes Rescue Cell Death and Preserve Mitochondrial Function in Parkinson's Disease

Leggio

L’Episcopo

Magrì

et al. 2022

Adv Healthcare Materials

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Extracellular vesicles (EVs) are emerging as powerful players in cell‐to‐cell communication both in healthy and diseased brain. In Parkinson's disease (PD)—characterized by selective dopaminergic neuron death in ventral midbrain (VMB) and degeneration of their terminals in striatum (STR)—astrocytes exert dual harmful/protective functions, with mechanisms not fully elucidated. Here, this study shows that astrocytes from the VMB‐, STR‐, and VMB/STR‐depleted brains release a population of small EVs in a region‐specific manner. Interestingly, VMB‐astrocytes secreted the highest rate of EVs, which is further exclusively increased in response to CCL3, a chemokine that promotes robust dopaminergic neuroprotection in different PD models. The neuroprotective potential of nigrostriatal astrocyte‐EVs is investigated in differentiated versus undifferentiated SH‐SY5Y cells exposed to oxidative stress and mitochondrial toxicity. EVs from both VMB‐ and STR‐astrocytes counteract H2O2‐induced caspase‐3 activation specifically in differentiated cells, with EVs from CCL3‐treated astrocytes showing a higher protective effect. High resolution respirometry further reveals that nigrostriatal astrocyte‐EVs rescue neuronal mitochondrial complex I function impaired by the neurotoxin MPP+. Notably, only EVs from VMB‐astrocyte fully restore ATP production, again specifically in differentiated SH‐SY5Y. These results highlight a regional diversity in the nigrostriatal system for the secretion and activities of astrocyte‐EVs, with neuroprotective implications for PD.

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“…After inoculation into the cisterna magna of EAE animals, these EVs are internalized by myeloid cells in the meningeal compartment and choroid plexus, reducing neuroinflammation and clinical signals (Casella et al., 2018). Likewise, EVs loaded with PKC agonists provide marked benefits in EAE animals and CPZ‐fed mice by acting on MG, favoring the transition of myeloid cells from a pro‐inflammatory to an anti‐inflammatory phenotype (Kornberg et al., 2018; Wu et al., 2022). Similarly, EVs derived from bone marrow MSC (BMSC) administered intravenously may affect the MG polarization, attenuating both demyelination and inflammation and restoring neurological function in EAE rats.…”

Section: Evs As Therapeutic Tools Targeting Mgmentioning

confidence: 99%

Microglia‐derived extracellular vesicles in homeostasis and demyelination/remyelination processes

Wies Mancini,

Mattera,

Pasquini

et al. 2023

Journal of Neurochemistry

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Microglia (MG) play a crucial role as the predominant myeloid cells in the central nervous system and are commonly activated in multiple sclerosis. They perform essential functions under normal conditions, such as actively surveying the surrounding parenchyma, facilitating synaptic remodeling, engulfing dead cells and debris, and protecting the brain against infectious pathogens and harmful self‐proteins. Extracellular vesicles (EVs) are diverse structures enclosed by a lipid bilayer that originate from intracellular endocytic trafficking or the plasma membrane. They are released by cells into the extracellular space and can be found in various bodily fluids. EVs have recently emerged as a communication mechanism between cells, enabling the transfer of functional proteins, lipids, different RNA species, and even fragments of DNA from donor cells. MG act as both source and recipient of EVs. Consequently, MG‐derived EVs are involved in regulating synapse development and maintaining homeostasis. These EVs also directly influence astrocytes, significantly increasing the release of inflammatory cytokines like IL‐1β, IL‐6, and TNF‐α, resulting in a robust inflammatory response. Furthermore, EVs derived from inflammatory MG have been found to inhibit remyelination, whereas Evs produced by pro‐regenerative MG effectively promote myelin repair. This review aims to provide an overview of the current understanding of MG‐derived Evs, their impact on neighboring cells, and the cellular microenvironment in normal conditions and pathological states, specifically focusing on demyelination and remyelination processes.

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Engineered extracellular vesicles encapsulated Bryostatin-1 as therapy for neuroinflammation

Abstract: Targeted and effective drug delivery to central nervous system (CNS) lesions is a major challenge in the treatment of multiple sclerosis (MS). Extracellular vesicles (EVs) have great promise as a...

Cited by 17 publications

References 49 publications

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications

Small Extracellular Vesicles Secreted by Nigrostriatal Astrocytes Rescue Cell Death and Preserve Mitochondrial Function in Parkinson's Disease

Microglia‐derived extracellular vesicles in homeostasis and demyelination/remyelination processes

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