Derivation of feeder-free human extended pluripotent stem cells
Published in Stem Cell Reports
Derivation of feeder-free human extended pluripotent stem cells
Challenging the pipeline
Published in Stem Cell Reports
In this commentary, Loskill and colleagues present a thought experiment seeking to answer the key question: “If you were to put aside all the traditional drug discovery processes and start a new drug discovery program that places the highest priority on human and disease-relevant models throughout the entire process, how could it be done?”
High-throughput screening on cochlear organoids identifies VEGFR-MEK-TGFB1 signaling promoting hair cell reprogramming
Published in Stem Cell Reports
Wan and colleagues report an optimized culture method for mouse cochlear organoids with over 6,000-fold increase in sample throughput. The authors show that both LGR5+ and LGR5–cochlear supporting cells can be differentiated into hair cells in the organoids. High-throughput screening of the organoids identified the VEGFR inhibitor regorafenib in pr...
Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition.
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Published in Stem cell reports
Neuromuscular junctions (NMJs) ensure communication between motor neurons (MNs) and muscle; however, in MN disorders, such as amyotrophic lateral sclerosis (ALS), NMJs degenerate resulting in muscle atrophy. The aim of this study was to establish a versatile and reproducible in vitro model of a human motor unit to investigate the effects of ALS-cau...
Human stem cell-based retina on chip as new translational model for validation of AAV retinal gene therapy vectors
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Published in Stem Cell Reports
Loskill and colleagues demonstrate that the retina on chip combining hiPSC-organoid and organ-on-chip technologies can serve as a novel translational tool for characterization and validation of AAV vectors by mimicking clinically relevant application routes. Seven AAVs were characterized in terms of transduction efficacy, cell tropism, and pharmaco...
Stem cell-based vascularization of microphysiological systems.
Published in Stem cell reports
Microphysiological systems (MPSs) (i.e., tissue or organ chips) exploit microfluidics and 3D cell culture to mimic tissue and organ-level physiology. The advent of human induced pluripotent stem cell (hiPSC) technology has accelerated the use of MPSs to study human disease in a range of organ systems. However, in the reduction of system complexity,...
Welcome to the special issue on organs-on-chip from the guest editors
Published in Stem Cell Reports
Engineered models of the human heart: Directions and challenges.
Published in Stem cell reports
Human heart (patho)physiology is now widely studied using human pluripotent stem cells, but the immaturity of derivative cardiomyocytes has largely limited disease modeling to conditions associated with mutations in cardiac ion channel genes. Recent advances in tissue engineering and organoids have, however, created new opportunities to study disea...
The aryl hydrocarbon receptor promotes differentiation during mouse preimplantational embryo development
Published in Stem Cell Reports
In this article, Fernández-Salguero and colleagues show that transcription factor AhR regulates pluripotency factors and maintains the metabolic activity required for proper embryo differentiation. AhR-lacking embryos ( AhR −/−) showed a pluripotent phenotype characterized by a delayed expression of trophectoderm differentiation markers. Accordingl...
Engineered 3D vessel-on-chip using hiPSC-derived endothelial- and vascular smooth muscle cells
Published in Stem Cell Reports
In this article, Orlova and colleagues describe the generation of an entirely human induced pluripotent stem cells (hiPSC)-derived vessel-on-chip composed with endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Changes in microvascular network architecture and intracellular Ca2+ release kinetics could be quantified during vascular or...
