Humanized brain organoids-on-chip integrated with sensors for screening neuronal activity and neurotoxicity

Saglam-Metiner, Pelin; Yildirim, Ender; Dincer, Can; Basak, Onur; Yesil-Celiktas, Ozlem

doi:10.1007/s00604-023-06165-4

Cited by 3 publications

(2 citation statements)

References 163 publications

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“…However, several limitations and challenges need to be addressed before brain organoids can be widely used for this purpose. The most relevant issue is the variability and reproducibility of brain organoid generation and maturation, which can affect the quality and consistency of the results [ 103 , 104 ]. To address this point, the development of standardized protocols and quality control methods for brain organoid generation and characterization is crucial.…”

Section: Conclusion and Future Prospectivementioning

confidence: 99%

Brain Organoids: A Game-Changer for Drug Testing

Giorgi,

Lombardozzi,

Ammannito

et al. 2024

Pharmaceutics

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Neurological disorders are the second cause of death and the leading cause of disability worldwide. Unfortunately, no cure exists for these disorders, but the actual therapies are only able to ameliorate people’s quality of life. Thus, there is an urgent need to test potential therapeutic approaches. Brain organoids are a possible valuable tool in the study of the brain, due to their ability to reproduce different brain regions and maturation stages; they can be used also as a tool for disease modelling and target identification of neurological disorders. Recently, brain organoids have been used in drug-screening processes, even if there are several limitations to overcome. This review focuses on the description of brain organoid development and drug-screening processes, discussing the advantages, challenges, and limitations of the use of organoids in modeling neurological diseases. We also highlighted the potential of testing novel therapeutic approaches. Finally, we examine the challenges and future directions to improve the drug-screening process.

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Section: Conclusion and Future Prospectivementioning

confidence: 99%

Brain Organoids: A Game-Changer for Drug Testing

Giorgi,

Lombardozzi,

Ammannito

et al. 2024

Pharmaceutics

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“…Although research utilizing organoids for electrophysiological studies offers many advantages for understanding the functionality of the human brain, significant advancements are still needed to faithfully mimic the activity of the adult brain ( 33 , 45 ). To overcome these limitations, recent efforts have been actively conducted to enhance the complexity and connectivity of organoids using technologies such as bioprinting and microfluidic chips ( 46 , 47 ). These studies could bridge the gap between human brains and organoids, opening possibilities to investigate electrophysiological features reminiscent of those observed in the human brain because of its complexity.…”

Section: Organoid-based Study Via Meamentioning

confidence: 99%

Electrophysiological insights with brain organoid models: a brief review

Kang,

Park,

Shin

et al. 2024

BMB Rep

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Brain organoid is a three-dimensional (3D) tissue derived from stem cells such as induced pluripotent stem cells (iPSCs) embryonic stem cells (ESCs) that reflect real human brain structure. It replicates the complexity and development of the human brain, enabling studies of the human brain in vitro . With emerging technologies, its application is various, including disease modeling and drug screening. A variety of experimental methods have been used to study structural and molecular characteristics of brain organoids. However, electrophysiological analysis is necessary to understand their functional characteristics and complexity. Although electrophysiological approaches have rapidly advanced for monolayered cells, there are some limitations in studying electrophysiological and neural network characteristics due to the lack of 3D characteristics. Herein, electrophysiological measurement and analytical methods related to neural complexity and 3D characteristics of brain organoids are reviewed. Overall, electrophysiological understanding of brain organoids allows us to overcome limitations of monolayer in vitro cell culture models, providing deep insights into the neural network complex of the real human brain and new ways of disease modeling.

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Comprehensive analysis of resilience of human airway epithelial barrier against short‐term PM2.5 inorganic dust exposure using in vitro microfluidic chip and ex vivo human airway models

Goksel,

Sipahi,

Yanasik

et al. 2024

Allergy

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Background and ObjectiveThe updated World Health Organization (WHO) air quality guideline recommends an annual mean concentration of fine particulate matter (PM2.5) not exceeding 5 or 15 μg/m3 in the short‐term (24 h) for no more than 3–4 days annually. However, more than 90% of the global population is currently exposed to daily concentrations surpassing these limits, especially during extreme weather conditions and due to transboundary dust transport influenced by climate change. Herein, the effect of respirable <PM2.5 inorganic silica particle exposures on epithelial barrier integrity was simultaneously evaluated within the biomimetic microfluidic platform‐based airway epithelial barrier (AEB)‐on‐a‐chip and human bronchoscopic ex vivo airway tissue models, comparatively.MethodsSilica particles at an average size of 1 μm, referred to as <PM2.5, dose‐dependently tested by MTT and LDH analyses. The elicited dose of 800 μg/mL was applied to human airway epithelial cells (Calu‐3) seeded to the membrane at air–liquid interface in the AEB‐on‐a‐chip platform, which is operated under static and dynamic conditions and to ex vivo human bronchoscopy bronchial tissue slices for 72 h. For both models, healthy and exposed groups were comparatively investigated. Computational fluid dynamics simulations were performed to assess shear stress profiles under different flow conditions. Qualitative and quantitative analyses were carried out to evaluate the resilience of the epithelial barrier via cell survivability, morphology, barrier integrity, permeability, and inflammation.ResultsIn the AEB‐on‐a‐chip platform, short‐term exposure to 800 μg/mL PM2.5 disrupted AEB integrity via increasing barrier permeability, decreasing cell adhesion‐barrier markers such as ZO‐1, Vinculin, ACE2, and CD31, impaired cell viability and increased the expression levels of proinflammatory markers; IFNs, IL‐6, IL‐1s, TNF‐α, CD68, CD80, and Inos, mostly under dynamic conditions. Besides, decreased tissue viability, impaired tissue integrity via decreasing of Vinculin, ACE2, β‐catenin, and E‐cadherin, and also proinflammatory response with elevated CD68, IL‐1α, IL‐6, IFN‐Ɣ, Inos, and CD80 markers, were observed after PM2.5 exposure in ex vivo tissue.ConclusionThe duration and concentration of PM2.5 that can be exposed during extreme weather conditions and natural events aligns with our exposure model (0–800 μg/mL 72 h). At this level of exposure, the resilience of the epithelial barrier is demonstrated by both AEB‐on‐a‐chip platform emulating dynamic forces in the body and ex vivo bronchial biopsy slices. Lung‐on‐a‐chip models will serve as reliable exposure models in this context.

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Humanized brain organoids-on-chip integrated with sensors for screening neuronal activity and neurotoxicity

Cited by 3 publications

References 163 publications

Brain Organoids: A Game-Changer for Drug Testing

Brain Organoids: A Game-Changer for Drug Testing

Electrophysiological insights with brain organoid models: a brief review

Comprehensive analysis of resilience of human airway epithelial barrier against short‐term PM2.5 inorganic dust exposure using in vitro microfluidic chip and ex vivo human airway models

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