Brain physiome: A concept bridging in vitro 3D brain models and in silico models for predicting drug toxicity in the brain

Seo, Yoojin; Bang, Seokyoung; Son, Jeongtae; Kim, Dongsup; Jeong, Yong; Kim, Pilnam; Yang, Ji-Hun; Eom, Joon-Ho; Choi, Nakwon; Kim, Hong Nam

doi:10.1016/j.bioactmat.2021.11.009

Cited by 15 publications

(11 citation statements)

References 166 publications

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“…In conclusion, future brain models should cover a wide field of applications in medicine, from those used for education, training and planning of surgery to those enabling the advanced study of medical device uses, notably their biocompatibility. Brain models, or phantoms, and digital brain models should learn from each other ( Seo et al, 2022 ). It is anticipated that artificial surrogates will integrate most biomechanical and biochemical properties of the living tissue.…”

Section: Discussionmentioning

confidence: 99%

A Minireview on Brain Models Simulating Geometrical, Physical, and Biochemical Properties of the Human Brain

Bouattour¹,

Sautou

Hmede

et al. 2022

Front. Bioeng. Biotechnol.

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There is a growing body of evidences that brain surrogates will be of great interest for researchers and physicians in the medical field. They are currently mainly used for education and training purposes or to verify the appropriate functionality of medical devices. Depending on the purpose, a variety of materials have been used with specific and accurate mechanical and biophysical properties, More recently they have been used to assess the biocompatibility of implantable devices, but they are still not validated to study the migration of leaching components from devices. This minireview shows the large diversity of approaches and uses of brain phantoms, which converge punctually. All these phantoms are complementary to numeric models, which benefit, reciprocally, of their respective advances. It also suggests avenues of research for the analysis of leaching components from implantable devices.

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Section: Discussionmentioning

confidence: 99%

A Minireview on Brain Models Simulating Geometrical, Physical, and Biochemical Properties of the Human Brain

Bouattour¹,

Sautou

Hmede

et al. 2022

Front. Bioeng. Biotechnol.

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“…To form the BBB, the perivascular endothelial cells, astrocytes, and pericytes that surround the central nervous system parenchyma work together [ 25 , 26 ]. The choroid plexus of the brain's ventricles is home to the BCSFB [ 27 ].…”

Section: Pathogenesis Of Brain Tumormentioning

confidence: 99%

Customizing delivery nano-vehicles for precise brain tumor therapy

et al. 2023

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Although some tumor has become a curable disease for many patients, involvement of the central nervous system (CNS) is still a major concern. The blood–brain barrier (BBB), a special structure in the CNS, protects the brain from bloodborne pathogens via its excellent barrier properties and hinders new drug development for brain tumor. Recent breakthroughs in nanotechnology have resulted in various nanovehicless (NPs) as drug carriers to cross the BBB by different strategys. Here, the complex compositions and special characteristics of causes of brain tumor formation and BBB are elucidated exhaustively. Additionally, versatile drug nanovehicles with their recent applications and their pathways on different drug delivery strategies to overcome the BBB obstacle for anti-brain tumor are briefly discussed. Customizing nanoparticles for brain tumor treatments is proposed to improve the efficacy of brain tumor treatments via drug delivery from the gut to the brain. This review provides a broad perspective on customizing delivery nano-vehicles characteristics facilitate drug distribution across the brain and pave the way for the creation of innovative nanotechnology-based nanomaterials for brain tumor treatments.

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“…The concept of an “organ on a chip” or 3D printing of organs, combining microfluidic systems and specialized extracellular matrices, has generated great interest and would meet the challenge of replicating CSF flow in models of the blood brain barrier ( Figure 1B ). This could be highly relevant for toxicity testing using patient-derived organoids and may allow the recreation of the brain “physiome” ( Seo et al, 2022 ).…”

Section: Future Directions and Challengesmentioning

confidence: 99%

Cerebral Organoids and Antisense Oligonucleotide Therapeutics: Challenges and Opportunities

Lange

Zhou

McTague

2022

Front. Mol. Neurosci.

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The advent of stem cell-derived cerebral organoids has already advanced our understanding of disease mechanisms in neurological diseases. Despite this, many remain without effective treatments, resulting in significant personal and societal health burden. Antisense oligonucleotides (ASOs) are one of the most widely used approaches for targeting RNA and modifying gene expression, with significant advancements in clinical trials for epilepsy, neuromuscular disorders and other neurological conditions. ASOs have further potential to address the unmet need in other neurological diseases for novel therapies which directly target the causative genes, allowing precision treatment. Induced pluripotent stem cell (iPSC) derived cerebral organoids represent an ideal platform in which to evaluate novel ASO therapies. In patient-derived organoids, disease-causing mutations can be studied in the native genetic milieu, opening the door to test personalized ASO therapies and n-of-1 approaches. In addition, CRISPR-Cas9 can be used to generate isogenic iPSCs to assess the effects of ASOs, by either creating disease-specific mutations or correcting available disease iPSC lines. Currently, ASO therapies face a number of challenges to wider translation, including insufficient uptake by distinct and preferential cell types in central nervous system and inability to cross the blood brain barrier necessitating intrathecal administration. Cerebral organoids provide a practical model to address and improve these limitations. In this review we will address the current use of organoids to test ASO therapies, opportunities for future applications and challenges including those inherent to cerebral organoids, issues with organoid transfection and choice of appropriate read-outs.

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Brain physiome: A concept bridging in vitro 3D brain models and in silico models for predicting drug toxicity in the brain

Cited by 15 publications

References 166 publications

A Minireview on Brain Models Simulating Geometrical, Physical, and Biochemical Properties of the Human Brain

A Minireview on Brain Models Simulating Geometrical, Physical, and Biochemical Properties of the Human Brain

Customizing delivery nano-vehicles for precise brain tumor therapy

Cerebral Organoids and Antisense Oligonucleotide Therapeutics: Challenges and Opportunities

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