Human cerebral organoids — a new tool for clinical neurology research

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(11), P. 661 - 680

Published: Oct. 17, 2022

Language: Английский

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Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 26, 2024

The induced pluripotent stem cell (iPSC) technology has transformed in vitro research and holds great promise to advance regenerative medicine. iPSCs have the capacity for an almost unlimited expansion, are amenable genetic engineering, can be differentiated into most somatic types. been widely applied model human development diseases, perform drug screening, develop therapies. In this review, we outline key developments iPSC field highlight immense versatility of modeling therapeutic applications. We begin by discussing pivotal discoveries that revealed potential a nucleus reprogramming led successful generation iPSCs. consider molecular mechanisms dynamics as well numerous methods available induce pluripotency. Subsequently, discuss various iPSC-based cellular models, from mono-cultures single type complex three-dimensional organoids, how these models elucidate diseases. use examples neurological disorders, coronavirus disease 2019 (COVID-19), cancer diversity disease-specific phenotypes modeled using iPSC-derived cells. also used high-throughput screening toxicity studies. Finally, process developing autologous allogeneic therapies their alleviate

Language: Английский

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Single-cell mapping of lipid metabolites using an infrared probe in human-derived model systems

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 8, 2024

Abstract Understanding metabolic heterogeneity is the key to uncovering underlying mechanisms of metabolic-related diseases. Current imaging studies suffer from limitations including low resolution and specificity, model systems utilized often lack human relevance. Here, we present a single-cell platform enable direct lipid metabolism with high specificity in various human-derived 2D 3D culture systems. Through incorporation an azide-tagged infrared probe, selective detection newly synthesized lipids cells tissue became possible, while simultaneous fluorescence enabled cell-type identification complex tissues. In proof-of-concept experiments, were directly visualized human-relevant among different cell types, mutation status, differentiation stages, over time. We identified upregulated progranulin-knockdown induced pluripotent stem their differentiated microglia cells. Furthermore, observed that neurons brain organoids exhibited significantly lower compared astrocytes.

Language: Английский

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Human brain organoid model of maternal immune activation identifies radial glia cells as selectively vulnerable

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(12), P. 5077 - 5089

Published: March 6, 2023

Abstract Maternal immune activation (MIA) during critical windows of gestation is correlated with long-term neurodevelopmental deficits in the offspring, including increased risk for autism spectrum disorder (ASD) humans. Interleukin 6 (IL-6) derived from gestational parent one major molecular mediators by which MIA alters developing brain. In this study, we establish a human three-dimensional (3D) vitro model treating induced pluripotent stem cell-derived dorsal forebrain organoids constitutively active form IL-6, Hyper-IL-6. We validate our showing that express machinery necessary responding to Hyper-IL-6 and activate STAT signaling upon treatment. RNA sequencing analysis reveals upregulation histocompatibility complex class I (MHCI) genes response exposure, have been implicated ASD. find small increase proportion radial glia cells after treatment through immunohistochemistry single-cell RNA-sequencing. further show are cell type highest number differentially expressed genes, leads downregulation related protein translation line mouse MIA. Additionally, identify not found models MIA, might drive species-specific responses Finally, abnormal cortical layering as consequence summary, 3D can be used study cellular mechanisms underlying disorders such

Language: Английский

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Flourishing tumor organoids: History, emerging technology, and application

Bioengineering & Translational Medicine, Journal Year: 2023, Volume and Issue: 8(5)

Published: June 7, 2023

Malignant tumors are one of the leading causes death which impose an increasingly heavy burden on all countries. Therefore, establishment research models that closely resemble original tumor characteristics is crucial to further understanding mechanisms malignant development, developing safer and more effective drugs, formulating personalized treatment plans. Recently, organoids have been widely used in owing their advantages including preserving structure, heterogeneity, cellular functions tumor, together with ease manipulation. This review describes history synergistic combination three-dimensional (3D) culture approaches for emerging technologies, tissue-engineered cell scaffolds, microfluidic devices, 3D bioprinting, rotating wall vessels, clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9). Additionally, progress applications basic clinical organoid summarized. includes studies mechanism drug development screening, precision medicine, immunotherapy, simulation microenvironment. Finally, existing shortcomings possible future directions discussed.

Language: Английский

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In vitro models to study human gut-microbiota interactions: Applications, advances, and limitations

Microbiological Research, Journal Year: 2023, Volume and Issue: 270, P. 127336 - 127336

Published: Feb. 16, 2023

Language: Английский

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Morphogenesis and development of human telencephalic organoids in the absence and presence of exogenous extracellular matrix

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(22)

Published: Oct. 16, 2023

The establishment and maintenance of apical-basal polarity is a fundamental step in brain development, instructing the organization neural progenitor cells (NPCs) developing cerebral cortex. Particularly, basally located extracellular matrix (ECM) crucial for this process. In vitro, epithelial polarization can be achieved via endogenous ECM production, or exogenous supplementation. While neuroepithelial development recapitulated organoids, effects different sources tissue morphogenesis remain underexplored. Here, we show that exposure to solubilized basement membrane substrate, Matrigel, at early stages causes rapid rearrangement architecture. cultures exposed pure components unexposed any ECM, acquisition slower driven by production. After onset neurogenesis, architecture neuronal differentiation are largely independent initial source, but Matrigel has long-lasting on patterning. These results advance knowledge mechanisms exogenously endogenously guided morphogenesis, demonstrating self-sustainability processes.

Language: Английский

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Organoids transplantation attenuates intestinal ischemia/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 25, 2023

Intestinal organoid transplantation is a promising therapy for the treatment of mucosal injury. However, how transplanted organoids regulate immune microenvironment recipient mice and their role in treating intestinal ischemia-reperfusion (I/R) injury remains unclear. Here, we establish method transplanting into I/R mice. We find that improve mouse survival, promote self-renewal stem cells after I/R, depending on enhanced ability macrophages polarized to an anti-inflammatory M2 phenotype. Specifically, report L-Malic acid (MA) highly expressed enriched organoids-derived conditioned medium cecal contents mice, demonstrating secrete MA during engraftment. Both vivo vitro experiments demonstrate induces macrophage polarization restores interleukin-10 levels SOCS2-dependent manner. This study provides therapeutic strategy

Language: Английский

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Technical challenges of studying early human development

Development, Journal Year: 2023, Volume and Issue: 150(11)

Published: June 1, 2023

ABSTRACT Recent years have seen exciting progress across human embryo research, including new methods for culturing embryos, transcriptional profiling of embryogenesis and gastrulation, mapping lineage trajectories, experimenting on stem cell-based models. These advances are beginning to define the dynamical principles development stages, tissues organs, enabling a better understanding before birth in health disease, potentially leading improved treatments infertility developmental disorders. However, there still significant roadblocks en route this goal. Here, we highlight technical challenges studying early propose ways means overcome some these constraints.

Language: Английский

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Nanoparticle-mediated thermal Cancer therapies: Strategies to improve clinical translatability

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 372, P. 751 - 777

Published: July 4, 2024

Despite significant advances, cancer remains a leading global cause of death. Current therapies often fail due to incomplete tumor removal and nonspecific targeting, spurring interest in alternative treatments. Hyperthermia, which uses elevated temperatures kill cells or boost their sensitivity radio/chemotherapy, has emerged as promising alternative. Recent advancements employ nanoparticles (NPs) heat mediators for selective cell destruction, minimizing damage healthy tissues. This approach, known NP hyperthermia, falls into two categories: photothermal (PTT) magnetothermal (MTT). PTT utilizes NPs that convert light heat, while MTT magnetic activated by alternating fields (AMF), both achieving localized damage. These methods offer advantages like precise minimal invasiveness, reduced systemic toxicity. However, the efficacy hyperthermia depends on many factors, particular, properties, microenvironment (TME), TME-NP interactions. Optimizing this treatment requires accurate monitoring strategies, such nanothermometry biologically relevant screening models can better mimic physiological features human body. review explores state-of-the-art NP-mediated discussing available nanomaterials, strengths weaknesses, characterization methods, future directions. Our particular focus lies preclinical techniques, providing an updated perspective relevance journey towards clinical trials.

Language: Английский

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