Human iPSC-Derived Neural Models for Studying Alzheimer’s Disease: from Neural Stem Cells to Cerebral Organoids

Stem Cell Reviews and Reports, Journal Year: 2022, Volume and Issue: 18(2), P. 792 - 820

Published: Feb. 1, 2022

During the past two decades, induced pluripotent stem cells (iPSCs) have been widely used to study mechanisms of human neural development, disease modeling, and drug discovery in vitro. Especially field Alzheimer's (AD), where this treatment is lacking, tremendous effort has put into investigation molecular behind using cell-based models. Numerous these studies found either novel regulatory that could be exploited develop relevant drugs for AD or already tested small molecules on vitro cultures, directly demonstrating their effect amelioration AD-associated pathology. This review thus summarizes currently differentiation strategies towards neuronal glial cell types cerebral organoids utilization modeling potential discovery.

Language: Английский

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Bioreactor Technologies for Enhanced Organoid Culture

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11427 - 11427

Published: July 13, 2023

An organoid is a 3D organization of cells that can recapitulate some the structure and function native tissue. Recent work has seen organoids gain prominence as valuable model for studying tissue development, drug discovery, potential clinical applications. The requirements successful culture in vitro differ significantly from those traditional monolayer cell cultures. generation maturation high-fidelity entails developing optimizing environmental conditions to provide optimal cues growth maturation, such oxygenation, mechanical fluidic activation, nutrition gradients, etc. To this end, we discuss four main categories bioreactors used culture: stirred (SBR), microfluidic (MFB), rotating wall vessels (RWV), electrically stimulating (ES) bioreactors. We aim lay out state-of-the-art both commercial in-house developed bioreactor systems, their benefits derived various tissues, limitations technology, including sterilization, accessibility, suitability ease use long-term culture. Finally, future directions improvements existing technology how they may be enhance specific

Language: Английский

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Pushing the boundaries of brain organoids to study Alzheimer’s disease

Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(8), P. 659 - 672

Published: June 22, 2023

Progression of Alzheimer's disease (AD) entails deterioration or aberrant function multiple brain cell types, eventually leading to neurodegeneration and cognitive decline. Defining how complex cell-cell interactions become dysregulated in AD requires novel human cell-based vitro platforms that could recapitulate the intricate cytoarchitecture diversity brain. Brain organoids (BOs) are 3D self-organizing tissues partially resemble architecture can AD-relevant pathology. In this review, we highlight versatile applications different types BOs model pathogenesis, including amyloid-β tau aggregation, neuroinflammation, myelin breakdown, vascular dysfunction, other phenotypes, as well accelerate therapeutic development for AD.

Language: Английский

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Vascularized human brain organoid on-chip

Lab on a Chip, Journal Year: 2023, Volume and Issue: 23(12), P. 2693 - 2709

Published: Jan. 1, 2023

We review the existing in vitro human brain models and elaborate on various strategies that enable curation of a vascularized organoid using microfluidic devices.

Language: Английский

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

Microchimica Acta, Journal Year: 2024, Volume and Issue: 191(1)

Published: Jan. 1, 2024

Language: Английский

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Strategies for modeling aging and age-related diseases

npj Aging, Journal Year: 2024, Volume and Issue: 10(1)

Published: July 10, 2024

Abstract The ability to reprogram patient-derived-somatic cells IPSCs (Induced Pluripotent Stem Cells) has led a better understanding of aging and age-related diseases like Parkinson’s, Alzheimer’s. established patient-derived disease models mimic pathology can be used design drugs for diseases. However, the age genetic mutations donor cells, employed reprogramming, differentiation protocol might often pose challenges in establishing an appropriate model. In this review, we will focus on various strategies successful reprogramming diseases, emphasizing accuracy recapitulation ways overcome limitations its potential application cell replacement therapy drug development.

Language: Английский

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Breaking Barriers in Huntington’s Disease Therapy: Focused Ultrasound for Targeted Drug Delivery

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(1)

Published: Jan. 3, 2025

Abstract Huntington’s disease (HD) is a progressive neurodegenerative resulting from mutation in the huntingtin (HTT) gene and characterized by motor dysfunction, cognitive decline, psychiatric disturbances. Currently, no disease-modifying treatments are available. Recent research has developed therapeutic agents that may have potential to directly target pathology, such as silencing or clearing mutant protein. However, these limited their inability cross blood-brain barrier (BBB), preventing optimal effects. Although various techniques been explored overcome BBB, focused ultrasound (FUS) emerged promising non-invasive modality offering for targeted intervention diseases, including HD. Preclinical studies demonstrated safety efficacy of FUS delivering agents, siRNAs AAV vector-based therapy, significant reductions HTT expression improvements function HD mouse models. Furthermore, profile FUS-induced BBB opening established clinical trials on human patients diseases other than HD, showing adverse effects brain structure function. This review provides comprehensive overview current state connects existing evidence with its promise establishing therapies Graphical

Language: Английский

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Two- and Three-Dimensional In Vitro Models of Parkinson’s and Alzheimer’s Diseases: State-of-the-Art and Applications

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 620 - 620

Published: Jan. 13, 2025

In vitro models play a pivotal role in advancing our understanding of neurodegenerative diseases (NDs) such as Parkinson’s and Alzheimer’s disease (PD AD). Traditionally, 2D cell cultures have been instrumental elucidating the cellular mechanisms underlying these diseases. Cultured cells derived from patients or animal provide valuable insights into pathological processes at level. However, they often lack native tissue environment complexity, limiting their ability to fully recapitulate features. contrast, 3D offer more physiologically relevant platform by mimicking brain architecture. These can incorporate multiple types, including neurons, astrocytes, microglia, creating microenvironment that closely resembles brain’s complexity. Bioengineering approaches allow researchers better replicate cell–cell interactions, neuronal connectivity, disease-related phenotypes. Both advantages limitations. While simplicity scalability for high-throughput screening basic processes, enhanced physiological relevance Integrating findings both model systems NDs, ultimately aiding development novel therapeutic strategies. Here, we review existing study PD AD.

Language: Английский

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“Focused Ultrasound-mediated Drug Delivery in Humans – a Path Towards Translation in Neurodegenerative Diseases”

Pharmaceutical Research, Journal Year: 2022, Volume and Issue: 39(3), P. 427 - 439

Published: March 1, 2022

Abstract The blood-brain barrier (BBB) has a major protective function in preventing the entry of harmful molecules into brain, but is simultaneously limiting delivery drugs, restricting their potential clinical application neurodegenerative diseases. Recent preclinical evidence demonstrates that following focused ultrasound with microbubbles (FUS+MB), BBB becomes reversibly accessible to compounds normally are brain-impermeable, suggesting FUS+MB as promising new platform for therapeutic agents central nervous system. As step towards translation, small cohort studies were performed demonstrating safe opening Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS) patients FUS+MB, however improved drug not yet been achieved human. Simultaneously, rapid progress human induced pluripotent stem cell (hiPSC) modeling technology allowed development novel patient-derived vitro model reacts can be used answer fundamental questions responses health disease. This review summarizes key features contribute limited delivery, recapitulates recent advances mediated vivo context disorders, highlights strategies fast-track translation improve bioavailability drugs brain. With effective application, this innovative may open avenues interventions diseases leading outcomes patients.

Language: Английский

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Human 3D brain organoids: steering the demolecularization of brain and neurological diseases

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: July 3, 2023

Abstract Understanding of human brain development, dysfunction and neurological diseases has remained limited challenging due to inability recapitulate brain-specific features in animal models. Though the anatomy physiology been understood a remarkable way using post-mortem, pathological samples models, however, modeling development remains challenge owing distinct complexity brain. In this perspective, three-dimensional (3D) organoids have shown beam light. Tremendous growth stem cell technologies permitted differentiation pluripotent cells under 3D culture conditions into organoids, which unique many ways also offer detailed investigation diseases. Their translational value emerged will benefit society once protocols for upscaling are place. Here, we summarize new advancements methods generation more complex including vascularized mixed lineage tissue from PSCs. How synthetic biomaterials microfluidic technology is boosting organoid highlighted. We discuss applications studying preterm birth associated dysfunction; viral infections mediated neuroinflammation, neurodevelopmental neurodegenerative highlight current challenges that field experiencing.

Language: Английский

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