Current Progress in the Creation, Characterization, and Application of Human Stem Cell-derived in Vitro Neuromuscular Junction Models

2021 ◽  
Author(s):  
Eileen Lynch ◽  
Emma Peek ◽  
Megan Reilly ◽  
Claire FitzGibbons ◽  
Samantha Robertson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neuromuscular Junction ◽  
Human Stem Cell ◽  
The Creation

scholarly journals A hydrogel platform for in vitro three dimensional assembly of human stem cell-derived islet cells and endothelial cells

2019 ◽  
Vol 97 ◽  
pp. 272-280 ◽  
Author(s):  
Punn Augsornworawat ◽  
Leonardo Velazco-Cruz ◽  
Jiwon Song ◽  
Jeffrey R. Millman
Keyword(s):  
Endothelial Cells ◽  
Stem Cell ◽  
Islet Cells ◽  
Three Dimensional ◽  
Human Stem Cell

scholarly journals Assessing Drug-Induced Long QT and Proarrhythmic Risk Using Human Stem-Cell-Derived Cardiomyocytes in a Ca2+ Imaging Assay: Evaluation of 28 CiPA Compounds at Three Test Sites

2019 ◽  
Vol 170 (2) ◽  
pp. 345-356 ◽  
Author(s):  
Hua Rong Lu ◽  
Haoyu Zeng ◽  
Ralf Kettenhofen ◽  
Liang Guo ◽  
Ivan Kopljar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Microelectrode Array ◽  
Torsade De Pointes ◽  
Transient Assay ◽  
Potential Drug ◽  
Human Stem Cell ◽  
Long Qt ◽  
Drug Induced ◽  
Vitro Assay

Abstract The goal of this research consortium including Janssen, MSD, Ncardia, FNCR/LBR, and Health and Environmental Sciences Institute (HESI) was to evaluate the utility of an additional in vitro assay technology to detect potential drug-induced long QT and torsade de pointes (TdP) risk by monitoring cytosolic free Ca2+ transients in human stem-cell-derived cardiomyocytes (hSC-CMs). The potential proarrhythmic risks of the 28 comprehensive in vitro proarrhythmia assay (CiPA) drugs linked to low, intermediate, and high clinical TdP risk were evaluated in a blinded manner using Ca2+-sensitive fluorescent dye assay recorded from a kinetic plate reader system (Hamamatsu FDSS/µCell and FDSS7000) in 2D cultures of 2 commercially available hSC-CM lines (Cor.4U and CDI iCell Cardiomyocytes) at 3 different test sites. The Ca2+ transient assay, performed at the 3 sites using the 2 different hSC-CMs lines, correctly detected potential drug-induced QT prolongation among the 28 CiPA drugs and detected cellular arrhythmias-like/early afterdepolarization in 7 of 8 high TdP-risk drugs (87.5%), 6 of 11 intermediate TdP-risk drugs (54.5%), and 0 of 9 low/no TdP-risk drugs (0%). The results were comparable among the 3 sites and from 2 hSC-CM cell lines. The Ca2+ transient assay can serve as a user-friendly and higher throughput alternative to complement the microelectrode array and voltage-sensing optical action potential recording assays used in the HESI-CiPA study for in vitro assessment of drug-induced long QT and TdP risk.

Validation of a novel human stem cell-based gene expression assay for in vitro DART assessment

2019 ◽  
Vol 88 ◽  
pp. 18-19
Author(s):  
Peter I. Racz ◽  
Inger Brandsma ◽  
Sabine Hartvelt ◽  
Tom Zwetsloot ◽  
Giel Hendriks
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Human Stem Cell ◽  
Gene Expression Assay

scholarly journals An In Vitro Model of Latency and Reactivation of Varicella Zoster Virus in Human Stem Cell-Derived Neurons

2015 ◽  
Vol 11 (6) ◽  
pp. e1004885 ◽  
Author(s):  
Amos Markus ◽  
Ilana Lebenthal-Loinger ◽  
In Hong Yang ◽  
Paul R. Kinchington ◽  
Ronald S. Goldstein
Keyword(s):  
Stem Cell ◽  
Varicella Zoster Virus ◽  
In Vitro Model ◽  
Human Stem Cell ◽  
Varicella Zoster ◽  
Vitro Model

scholarly journals In Vitro Differentiated Human Stem Cell-Derived Neurons Reproduce Synaptic Synchronicity Arising during Neurodevelopment

2020 ◽  
Vol 15 (1) ◽  
pp. 22-37 ◽  
Author(s):  
Filip Rosa ◽  
Ashutosh Dhingra ◽  
Betül Uysal ◽  
G. Dulini C. Mendis ◽  
Heidi Loeffler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Stem Cell

Human stem cell-derived encapsulated liver tissue as an effective, consistent and long-lasting in vitro tool for drug testing and development

2017 ◽  
Vol 49 (4) ◽  
pp. e251
Author(s):  
C. Raggi ◽  
M. M’Callum ◽  
C. Mangahas ◽  
Z. Cohen ◽  
A. Shikanov ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Tissue ◽  
Drug Testing ◽  
Human Stem Cell

scholarly journals A human stem cell-derived neurosensory-epithelial circuitry on-a-chip to model herpes simplex virus reactivation

2020 ◽  
Author(s):  
Pietro Giuseppe Mazzara ◽  
Elena Criscuolo ◽  
Marco Rasponi ◽  
Luca Massimino ◽  
Sharon Muggeo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Sensory Neurons ◽  
Viral Latency ◽  
Human Stem Cell ◽  
Cell Type ◽  
Viral Pathogens ◽  
Simplex Virus

AbstractBoth emerging viruses and well-known viral pathogens endowed with neurotropism can either impair directly the neuronal functions or induce physio-pathological changes by diffusing from the periphery through neurosensory-epithelial connections. However, the current lack of an in vitro system modeling the connectivity between human neurons and peripheral tissues excludes the analysis of viral latency and reactivation and the assessment of natural/artificial induced anti-viral immunity. In this study, we developed the first stable topographic neurosensory-epithelial connection on-a-chip using human stem cell derived dorsal root ganglia (DRG) sensory neurons. Bulk and single cell transcriptomics showed that different combinations of key receptors for Herpes Simplex Virus 1 (HSV-1) are expressed by each sensory neuronal cell type. This neuronal-epithelial circuitry enabled a detailed analysis of the HSV infectivity faithfully modeling its dynamics and cell type specificity. The reconstitution of an organized connectivity between human sensory neurons and keratinocytes into microfluidic chips provides for the first time a powerful in vitro platform to model viral latency and reactivation of human viral pathogens.

scholarly journals Machine Learning Identifies Cellular and Exosomal MicroRNA Signatures of Lyssavirus Infection in Human Stem Cell-Derived Neurons

2021 ◽  
Vol 11 ◽  
Author(s):  
Ryan J. Farr ◽  
Nathan Godde ◽  
Christopher Cowled ◽  
Vinod Sundaramoorthy ◽  
Diane Green ◽  
...  
Keyword(s):  
Machine Learning ◽  
Stem Cell ◽  
Differential Expression Analysis ◽  
Machine Learning Algorithms ◽  
Supervised Machine Learning ◽  
P Value ◽  
Human Stem Cell ◽  
Cellular Mirnas ◽  
Neural Lineage

Despite being vaccine preventable, rabies (lyssavirus) still has a significant impact on global mortality, disproportionally affecting children under 15 years of age. This neurotropic virus is deft at avoiding the immune system while travelling through neurons to the brain. Until recently, research efforts into the role of non-coding RNAs in rabies pathogenicity and detection have been hampered by a lack of human in vitro neuronal models. Here, we utilized our previously described human stem cell-derived neural model to investigate the effect of lyssavirus infection on microRNA (miRNA) expression in human neural cells and their secreted exosomes. Conventional differential expression analysis identified 25 cellular and 16 exosomal miRNAs that were significantly altered (FDR adjusted P-value <0.05) in response to different lyssavirus strains. Supervised machine learning algorithms determined 6 cellular miRNAs (miR-99b-5p, miR-346, miR-5701, miR-138-2-3p, miR-651-5p, and miR-7977) were indicative of lyssavirus infection (100% accuracy), with the first four miRNAs having previously established roles in neuronal function, or panic and impulsivity-related behaviors. Another 4-miRNA signatures in exosomes (miR-25-3p, miR-26b-5p, miR-218-5p, miR-598-3p) can independently predict lyssavirus infected cells with >99% accuracy. Identification of these robust lyssavirus miRNA signatures offers further insight into neural lineage responses to infection and provides a foundation for utilizing exosome miRNAs in the development of next-generation molecular diagnostics for rabies.

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