Manufacturing Uniform Cerebral Organoids for Neurological Disease Modeling and Drug Evaluation DOI Creative Commons
Hyowon Hong, Yesl Jun, Sae‐Bom Yoon

и другие.

Biomaterials Research, Год журнала: 2024, Номер 28

Опубликована: Янв. 1, 2024

Human cerebral organoids are promising tools for investigating brain development and the pathogenesis underlying neurological disorders. To use drug effectiveness safety screening, dispensed into each well must be prepared under precisely same conditions as cells. Despite decades of extensive research on approaches to improve organoid generation, various challenges remain, such low yields heterogeneity in size differentiation both within between batches. Here, we newly established uniform (UCOs) derived from induced pluripotent stem cells by optimizing performing real-time monitoring telencephalic marker expression. These exhibited morphological uniformity consistent expression FOXG1 during differentiation, with high productivity. Moreover, UCOs faithfully recapitulated early corticogenesis, concomitant establishment neuroepithelial populations, cortical plate neurons, glial Furthermore, systematically developed neural networks excitatory inhibitory electrophysiological signals when exposed neurotransmission blockers. Neurodevelopmental disease models manifested neurite outgrowth defects, which could ameliorated targeted treatment. We propose an advanced platform variations reproducibility modeling diseases.

Язык: Английский

The Use of Neurons Derived from Pluripotent Stem Cells to Study Nerve–Cancer Cell Interactions DOI Open Access
Adriana Jiménez, Adolfo López-Ornelas,

Noelia Cruz

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3057 - 3057

Опубликована: Март 27, 2025

Tumor innervation is a complex interaction between nerves and cancer cells that consists of axons invading tumors, its complexity remains largely unknown in humans. Although some retrospective studies have provided important insights into the relationship further knowledge required about this biological process. Animal experiments elucidated several molecular cellular mechanisms tumor innervation; however, no experimental models currently exist to study interactions human nerve cells. Human pluripotent stem can differentiate neurons for research purposes; use these with unexplored. Hence, here we analyze potential derived from unravel poorly understood innervation.

Язык: Английский

Процитировано

0

A Compound Screen Based on Isogenic hESC‐Derived β Cell Reveals an Inhibitor Targeting ZnT8‐Mediated Zinc Transportation to Protect Pancreatic β Cell from Stress‐Induced Cell Death DOI Creative Commons
Rui Hu, Qing Ma, Yunhui Kong

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Abstract Pancreatic β cell loss by cellular stress contributes to diabetes pathogenesis. Nevertheless, the fundamental mechanism of regulation remains elusive. Here, it is found that elevated zinc transportation causes excessive in pancreatic cells diabetes. With gene‐edited human embryonic stem cell‐derived (SC‐β cells) and primary islets, results reveal initiates integrated response (ISR), ultimately leads death. By contrary, genetic abolishment shields from exacerbated endoplasmic reticulum (ER stress) concurrent ISR. To target with a chemical inhibitor, an isogenic SC‐β based drug‐screening platform established. Surprisingly, independent its traditional role as protein synthesis inhibitor at high‐dose (10 µ m ), low‐dose (25 n ) anisomycin significantly inhibits effectively prevents loss. Remarkably, vivo administration mice demonstrates protective effects on type 2 induced high‐fat diet. Overall, identified crucial driver potential therapeutic molecule for

Язык: Английский

Процитировано

0

Emerging Human Pluripotent Stem Cell-Based Human–Animal Brain Chimeras for Advancing Disease Modeling and Cell Therapy for Neurological Disorders DOI

Yanru Ji,

Jenna Lillie McLean,

Ranjie Xu

и другие.

Neuroscience Bulletin, Год журнала: 2024, Номер 40(9), С. 1315 - 1332

Опубликована: Март 11, 2024

Язык: Английский

Процитировано

3

An FDA-Validated, Self-Cleaning Liquid Chromatography–Mass Spectrometry System for Determining Small-Molecule Drugs and Metabolites in Organoid/Organ-on-Chip Medium DOI Creative Commons
Stian Kogler,

Gustav Mathingsdal Pedersen,

Felipe Martínez-Ramírez

и другие.

Analytical Chemistry, Год журнала: 2024, Номер 96(29), С. 12129 - 12138

Опубликована: Июль 10, 2024

As organoids and organ-on-chip (OoC) systems move toward preclinical clinical applications, there is an increased need for method validation. Using a liquid chromatography-mass spectrometry (LC-MS)-based approach, we developed measuring small-molecule drugs metabolites in the cell medium directly sampled from liver organoids/OoC systems. The LC-MS setup was coupled to automatic filtration filter flush system with online solid-phase extraction (SPE), allowing robust automated sample cleanup/analysis. For matrix, rich in, e.g., protein, salts, amino acids, no preinjection preparation steps (protein precipitation, SPE, etc.) were necessary. approach demonstrated tolbutamide its metabolite, 4-hydroxytolbutamide (4HT). validated analysis of media human stem cell-derived cultured static conditions on microfluidic platform according Food Drug Administration (FDA) guidelines regards selectivity, matrix effects, accuracy, precision, etc. allows hundreds injections without replacing chromatography hardware. In summary, drug/metabolite organoids/OoCs can be performed robustly minimal preparation.

Язык: Английский

Процитировано

3

Manufacturing Uniform Cerebral Organoids for Neurological Disease Modeling and Drug Evaluation DOI Creative Commons
Hyowon Hong, Yesl Jun, Sae‐Bom Yoon

и другие.

Biomaterials Research, Год журнала: 2024, Номер 28

Опубликована: Янв. 1, 2024

Human cerebral organoids are promising tools for investigating brain development and the pathogenesis underlying neurological disorders. To use drug effectiveness safety screening, dispensed into each well must be prepared under precisely same conditions as cells. Despite decades of extensive research on approaches to improve organoid generation, various challenges remain, such low yields heterogeneity in size differentiation both within between batches. Here, we newly established uniform (UCOs) derived from induced pluripotent stem cells by optimizing performing real-time monitoring telencephalic marker expression. These exhibited morphological uniformity consistent expression FOXG1 during differentiation, with high productivity. Moreover, UCOs faithfully recapitulated early corticogenesis, concomitant establishment neuroepithelial populations, cortical plate neurons, glial Furthermore, systematically developed neural networks excitatory inhibitory electrophysiological signals when exposed neurotransmission blockers. Neurodevelopmental disease models manifested neurite outgrowth defects, which could ameliorated targeted treatment. We propose an advanced platform variations reproducibility modeling diseases.

Язык: Английский

Процитировано

3