Phase resetting in human stem cell derived cardiomyocytes explains complex cardiac arrhythmias

To the Editor: The molecular mechanisms and the control of smooth muscle cell (SMC) differentiation have been extensively investigated because of its therapeutic potential.1 To date, different cell types have been used to study SMC differentiation, including a variety of mouse embryonic stem cells,2 adult stem cells,3,4 and others.5 Because several fundamental differences exist between mouse and human embryonic development,6 lack of a good model system to study human SMC differentiation has hampered the progress of translating SMC knowledge to novel clinical therapies. Human embryonic stem (hES) cells provide a valuable source of cells for studying human cell differentiation and developing therapeutic potentials in regenerative medicine. Since the initial report describing the derivation of hES cells,7 a variety of studies have established in vitro differentiation strategies to several lineages. Recently, it has been demonstrated that vascular progenitors derived from hES cells could be differentiated into endothelial cells and SMCs by endothelial …

Translation: Screening for Novel Therapeutics With Disease-Relevant Cell Types Derived from Human Stem Cell Models

Rapid and Efficient Generation of Functional Motor Neurons From Human Pluripotent Stem Cells Using Gene Delivered Transcription Factor Codes

A PITX3-EGFP Reporter Line Reveals Connectivity of Dopamine and Non-dopamine Neuronal Subtypes in Grafts Generated from Human Embryonic Stem Cells.

Toxicology has long relied on animal models in a tedious approach to understanding risk of exposure to an uncharacterized molecule. Stem cell-derived tissues can be made in high purity, quality, and quantity to enable a new approach to this problem. Currently, stem cell-derived tissues are primarily "generic" genetic backgrounds; the future will see the integration of various genetic backgrounds and complex three-dimensional models to create truly unique in vitro organoids. This minireview focuses on the state of the art of a number of stem cell-derived tissues and details their application in toxicology.

The phase resetting response of the human circadian pacemaker to light depends on the timing of exposure and is described by a phase response curve (PRC). The current study aimed to construct a PRC for a 1 h exposure to bright white light (∼8000 lux) and to compare this PRC to a <3 lux dim background light PRC. These data were also compared to a previously completed 6.7 h bright white light PRC and a <15 lux dim background light PRC constructed under similar conditions. Participants were randomized for exposure to 1 h of either bright white light (n=18) or <3 lux dim background light (n=18) scheduled at 1 of 18 circadian phases. Participants completed constant routine (CR) procedures in dim light (<3 lux) before and after the light exposure to assess circadian phase. Phase shifts were calculated as the difference in timing of dim light melatonin onset (DLMO) during pre- and post-stimulus CRs. Exposure to 1 h of bright white light induced a Type 1 PRC with a fitted peak-to-trough amplitude of 2.20 h. No discernible PRC was observed in the <3 lux dim background light PRC. The fitted peak-to-trough amplitude of the 1 h bright light PRC was ∼40% of that for the 6.7 h PRC despite representing only 15% of the light exposure duration, consistent with previous studies showing a non-linear duration–response function for the effects of light on circadian resetting.

Promise of Human Induced Pluripotent Stem Cells in Skin Regeneration and Investigation

Event Abstract Back to Event Human stem cell culture and detachment on biomaterials immobilized with thermoresponsive nanobrush Yi Tung Lu1, Yen Ming Chen1*, Hong Ren Lin1 and Akon Higuchi1, 2* 1 National Central University, Chemical and Materials Engineering, Taiwan 2 King Saud University, Botany and Microbiology, Saudi Arabia Thermoresponsive surface prepared using thermoresponsive polymers with low critical solution temperatures (LCSTs) is attractive candidates for stem cell culture because stem cells can be detached from the surface without applying an enzymatic digestion method and, instead, by decreasing the temperature, which enables cell aggregates or cell sheets to be obtained in culture medium. In this study, we designed the thermoresponsive nano-brush surfaces for human stem cell culture (human adipose-derived stem cells [hADSCs] and human pluripotent stem cells [hPSCs]). Using RAFT polymerization, we prepared the coating copolymers having polystyrene and (a) thermoresponsive poly(N-isopropyl acrylamide), PNIPAAm[1], (b) biocompatible polyethylene glycol methacrylate (PEGMA), and (c) polyacrylic acid (PAA) where bioactive oligopeptide (oligo-vitronectin)[2],[3] can be conjugated via carboxylic acid of PAA. hADSCs were cultured on the surface coated with copolymers containing PNIPAAm, PEGMA and PAA conjugated with oligo-vitronectin. The optimal surface composition where hADSCs can attach and detach by decreasing temperature was investigated. Furthermore, human embryonic stem cells (WA09) and human induced pluripotent stem cells were cultured on the surface coated with these copolymers. We have successfully cultured human stem cells on the thermoresponsive nanobrush surface and can reach 80% cell detachment of hADSCs and 50% cell detachment of hESCs. However, if we could not reach 100% detachment of stem cells, we have another option that thermoresponsive nanobrush surfaces can be reused with partial detachment of stem cells, which do not need the process to reseed cells (passage). We also investigated whether hPSCs could maintain their pluripotency on the surface coated with these copolymers to find out long period (>passage ten) and whether hPSCs could be easily detach from the surface by decreasing the temperature. This results indicate that human stem cells which are highly sensitive to enzymatic treatment can be achieved by used copolymer nanobrush surfaces. Furthermore, we are designing to shift to a novel 3D culture system to scale up for clinical application. Akon Higuchi; Yen Ming Chen; Hong Ren Lin; Saradaprasan Muduli; I Chia Peng; Hsing Fen Li

CXCL12/CXCR4 Signaling Enhances Human PSC-Derived Hematopoietic ProgenitorFunction and Overcomes Early InVivo Transplantation Failure.

British Society for Gene and Cell Therapy Autumn Conference Friday 23 November 2018 Regent's University Conference Centre, London, UK www.bsgct.org

Fluorescent Gene Tagging of Transcriptionally Silent Genes in hiPSCs.

Stabilization of hESCs in two distinct substates along the continuum of pluripotency.

Remodeling Neurodegeneration: Somatic Cell Reprogramming-Based Models of Adult Neurological Disorders

Human pluripotent stem cells (hPSC) have great clinical potential through the use of their differentiated progeny, a population in which there is some concern over risks of tumorigenicity or other unwanted cellular behavior due to residual hPSC. Preclinical studies using human stem cells are most often performed within a xenotransplant context. In this study, we sought to measure how undifferentiated hPSC behave following xenotransplant. We directly transplanted undifferentiated human induced pluripotent stem cells (hIPSC) and human embryonic stem cells (hESC) into the adult mouse brain ventricle and analyzed their fates. No tumors or precancerous lesions were present at more than one year after transplantation. This result differed with the tumorigenic capacity we observed after allotransplantation of mouse ESC into the mouse brain. A substantial population of cellular derivatives of undifferentiated hESC and hIPSC engrafted, survived, and migrated within the mouse brain parenchyma. Within brain structures, transplanted cell distribution followed a very specific pattern, suggesting the existence of distinct microenvironments that offer different degrees of permissibility for engraftment. Most of the transplanted hESC and hIPSC that developed into brain cells were NeuN+ neuronal cells, and no astrocytes were detected. Substantial cell and nuclear fusion occurred between host and transplanted cells, a phenomenon influenced by microenvironment. Overall, hIPSC appear to be largely functionally equivalent to hESC in vivo. Altogether, these data bring new insights into the behavior of stem cells without prior differentiation following xenotransplantation into the adult brain.

Gene Correction in Human Embryonic and Induced Pluripotent Stem Cells: Promises and Challenges Ahead