Variations in Aspects of Neural Precursor Cell Neurogenesis in a Human Model of HSV-1 Infection

Zheng, Wenxiao; Benner, Emily M; Bloom, David C.; Muralidaran, Vaishali; Caldwell, Jill K.; Prabhudesai, Anuya; Piazza, Paolo; Wood, Joel; Kinchington, Paul R.; Nimgaonkar, Vishwajit L.; D’Aiuto, Leonardo

doi:10.1080/15476278.2022.2055354

Cited by 4 publications

(3 citation statements)

References 28 publications

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“…The neural precursor cells (NPCs) derived 58 from human induced pluripotent stem cell (hiPSC) line SC0000020 (subclone SF) (generated at RUCDR Infinite Biologics, Piscataway, NJ, USA) were maintained in STEMdiff Neural Progenitor Medium (05833, STEMCELL Technologies, Vancouver, BC, Canada). The iPSCs were generated using fibroblasts derived from skin biopsies collected from control individuals.…”

Section: Methodsmentioning

confidence: 99%

A multicellular brain spheroid model for studying the mechanisms and bioeffects of ultrasound-enhanced drug penetration beyond the blood‒brain barrier

Paranjape,

D’Aiuto,

Zheng

et al. 2024

Sci Rep

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The blood‒brain barrier (BBB) acts as a hindrance to drug therapy reaching the brain. With an increasing incidence of neurovascular diseases and brain cancer metastases, there is a need for an ideal in vitro model to develop novel methodologies for enhancing drug delivery to the brain. Here, we established a multicellular human brain spheroid model that mimics the BBB both architecturally and functionally. Within the spheroids, endothelial cells and pericytes localized to the periphery, while neurons, astrocytes, and microglia were distributed throughout. Ultrasound-targeted microbubble cavitation (UTMC) is a novel noninvasive technology for enhancing endothelial drug permeability. We utilized our three-dimensional (3D) model to study the feasibility and mechanisms regulating UTMC-induced hyperpermeability. UTMC caused a significant increase in the penetration of 10 kDa Texas red dextran (TRD) into the spheroids, 100 µm beyond the BBB, without compromising cell viability. This hyperpermeability was dependent on UTMC-induced calcium (Ca2+) influx and endothelial nitric oxide synthase (eNOS) activation. Our 3D brain spheroid model, with its intact and functional BBB, offers a valuable platform for studying the bioeffects of UTMC, including effects occurring spatially distant from the endothelial barrier.

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Section: Methodsmentioning

confidence: 99%

A multicellular brain spheroid model for studying the mechanisms and bioeffects of ultrasound-enhanced drug penetration beyond the blood‒brain barrier

Paranjape,

D’Aiuto,

Zheng

et al. 2024

Sci Rep

Self Cite

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show abstract

“…Prior studies have been limited to the modeling of rare single-gene inborn errors of immunity in hiPSC-derived CNS cells from human fibroblasts (Lafaille et al 2012 ; Zimmer et al 2018 ; Chansard et al 2021 ). A recent study (Zheng et al 2022 ) compared the effects of HSV-1 infection at low multiplicity of infection on the proliferation and migration of two hiPSC-derived NPC lines from a healthy woman (02SF) and her son (01SD). HSV-1 was reported to affect the proliferative activity of 02SF and 01SD NPCs in a viral dose-dependent trend, with a difference in the transcriptional activity of HSV-1 genes.…”

Section: Three-dimensional (3d) Brain Organoid Culturesmentioning

confidence: 99%

iPSC-derived three-dimensional brain organoid models and neurotropic viral infections

et al. 2023

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Progress in stem cell research has revolutionized the medical field for more than two decades. More recently, the discovery of induced pluripotent stem cells (iPSCs) has allowed for the development of advanced disease modeling and tissue engineering platforms. iPSCs are generated from adult somatic cells by reprogramming them into an embryonic-like state via the expression of transcription factors required for establishing pluripotency. In the context of the central nervous system (CNS), iPSCs have the potential to differentiate into a wide variety of brain cell types including neurons, astrocytes, microglial cells, endothelial cells, and oligodendrocytes. iPSCs can be used to generate brain organoids by using a constructive approach in three-dimensional (3D) culture in vitro. Recent advances in 3D brain organoid modeling have provided access to a better understanding of cell-to-cell interactions in disease progression, particularly with neurotropic viral infections. Neurotropic viral infections have been difficult to study in two-dimensional culture systems in vitro due to the lack of a multicellular composition of CNS cell networks. In recent years, 3D brain organoids have been preferred for modeling neurotropic viral diseases and have provided invaluable information for better understanding the molecular regulation of viral infection and cellular responses. Here we provide a comprehensive review of the literature on recent advances in iPSC-derived 3D brain organoid culturing and their utilization in modeling major neurotropic viral infections including HIV-1, HSV-1, JCV, ZIKV, CMV, and SARS-CoV2.

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“…Sample Preparation, Immunohistochemical Staining, Microscopy and Imaging, Image Analysis, Quantitative Measurements, Interpreting Results. The article outlines the specific reagents and process details, but it's important to note that real-world experiments might involve some modifications [17] .…”

Section: Quantification Of Aβ Loadmentioning

confidence: 99%

APOE-ε4 genes may accelerate the activation of the latent form of HSV-1 which would lead to a faster progression of AD

Tang

2023

BIO Web Conf.

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This study investigates the impact of APOE alleles and latent Herpes Simplex Type 1 virus (HSV-1) activation on Alzheimer’s disease (AD) progression using the 5xFAD mouse model. APOE ε4 is recognized as a substantial genetic risk factor for sporadic AD, while HSV-1 has been linked to AD pathogenesis through inflammation and plaque formation. The experimental approach involves the introduction of human neurons carrying latent HSV-1 into 5xFAD mice harboring various APOE alleles (APOE2, APOE3, APOE4), along with stress induction and pharmacological interventions. The study aims to elucidate the combined impact of these variables on AD progression and the formation of Aβ plaques. Our anticipated results suggest that APOE ε4 may accelerate AD development, especially in conjunction with HSV-1 activation, while APOE ε2 may exert a mitigating influence. These findings have the potential to advance our understanding of the intricate mechanisms underpinning AD and provide insights into potential therapeutic approaches. Further exploration of these interactions could offer critical insights into the pursuit of effective AD treatments.

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Variations in Aspects of Neural Precursor Cell Neurogenesis in a Human Model of HSV-1 Infection

Cited by 4 publications

References 28 publications

A multicellular brain spheroid model for studying the mechanisms and bioeffects of ultrasound-enhanced drug penetration beyond the blood‒brain barrier

A multicellular brain spheroid model for studying the mechanisms and bioeffects of ultrasound-enhanced drug penetration beyond the blood‒brain barrier

iPSC-derived three-dimensional brain organoid models and neurotropic viral infections

APOE-ε4 genes may accelerate the activation of the latent form of HSV-1 which would lead to a faster progression of AD

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