scholarly journals Modeling Neurological Disorders with Human Pluripotent Stem Cell-Derived Astrocytes

2019 ◽  
Vol 20 (16) ◽  
pp. 3862 ◽  
Author(s):  
Mika Suga ◽  
Takayuki Kondo ◽  
Haruhisa Inoue
Keyword(s):  
Stem Cell ◽  
Neurological Disorders ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Human Diseases ◽  
Human Pluripotent Stem Cell ◽  
Human Astrocytes ◽  
Induced Pluripotent ◽  
Human Ipsc

Astrocytes play vital roles in neurological disorders. The use of human induced pluripotent stem cell (iPSC)-derived astrocytes provides a chance to explore the contributions of astrocytes in human diseases. Here we review human iPSC-based models for neurological disorders associated with human astrocytes and discuss the points of each model.

scholarly journals Personalized medicine in cardio-oncology: the role of induced pluripotent stem cell

2019 ◽  
Vol 115 (5) ◽  
pp. 949-959 ◽  
Author(s):  
Nazish Sayed ◽  
Mohamed Ameen ◽  
Joseph C Wu
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Association Studies ◽  
Induced Pluripotent Stem Cell ◽  
Human Diseases ◽  
Genome Wide Association Studies ◽  
Genomic Variants ◽  
Induced Pluripotent

Abstract Treatment of cancer has evolved in the last decade with the introduction of new therapies. Despite these successes, the lingering cardiotoxic side-effects from chemotherapy remain a major cause of morbidity and mortality in cancer survivors. These effects can develop acutely during treatment, or even years later. Although many risk factors can be identified prior to beginning therapy, unexpected toxicity still occurs, often with lasting consequences. Specifically, cardiotoxicity results in cardiac cell death, eventually leading to cardiomyopathy and heart failure. Certain risk factors may predispose an individual to experiencing adverse cardiovascular effects, and when unexpected cardiotoxicity occurs, it is generally managed with supportive care. Animal models of chemotherapy-induced cardiotoxicity have provided some mechanistic insights, but the precise mechanisms by which these drugs affect the heart remains unknown. Moreover, the genetic rationale as to why some patients are more susceptible to developing cardiotoxicity has yet to be determined. Many genome-wide association studies have identified genomic variants that could be associated with chemotherapy-induced cardiotoxicity, but the lack of validation has made these studies more speculative rather than definitive. With the advent of human induced pluripotent stem cell (iPSC) technology, researchers not only have the opportunity to model human diseases, but also to screen drugs for their efficacy and toxicity using human cell models. Furthermore, it allows us to conduct validation studies to confirm the role of genomic variants in human diseases. In this review, we discuss the role of iPSCs in modelling chemotherapy-induced cardiotoxicity.

scholarly journals Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes as Models for Genetic Cardiomyopathies

2019 ◽  
Vol 20 (18) ◽  
pp. 4381 ◽  
Author(s):  
Andreas Brodehl ◽  
Hans Ebbinghaus ◽  
Marcus-André Deutsch ◽  
Jan Gummert ◽  
Anna Gärtner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Promising Alternative ◽  
Human Ipscs ◽  
Genetic Landscape ◽  
Inherited Cardiomyopathies ◽  
Induced Pluripotent ◽  
Human Ipsc

In the last few decades, many pathogenic or likely pathogenic genetic mutations in over hundred different genes have been described for non-ischemic, genetic cardiomyopathies. However, the functional knowledge about most of these mutations is still limited because the generation of adequate animal models is time-consuming and challenging. Therefore, human induced pluripotent stem cells (iPSCs) carrying specific cardiomyopathy-associated mutations are a promising alternative. Since the original discovery that pluripotency can be artificially induced by the expression of different transcription factors, various patient-specific-induced pluripotent stem cell lines have been generated to model non-ischemic, genetic cardiomyopathies in vitro. In this review, we describe the genetic landscape of non-ischemic, genetic cardiomyopathies and give an overview about different human iPSC lines, which have been developed for the disease modeling of inherited cardiomyopathies. We summarize different methods and protocols for the general differentiation of human iPSCs into cardiomyocytes. In addition, we describe methods and technologies to investigate functionally human iPSC-derived cardiomyocytes. Furthermore, we summarize novel genome editing approaches for the genetic manipulation of human iPSCs. This review provides an overview about the genetic landscape of inherited cardiomyopathies with a focus on iPSC technology, which might be of interest for clinicians and basic scientists interested in genetic cardiomyopathies.

Pig Induced Pluripotent Stem Cell-Derived Neural Rosettes Developmentally Mimic Human Pluripotent Stem Cell Neural Differentiation

2015 ◽  
Vol 24 (16) ◽  
pp. 1901-1911 ◽  
Author(s):  
Amalia Gallegos-Cárdenas ◽  
Robin Webb ◽  
Erin Jordan ◽  
Rachel West ◽  
Franklin D. West ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neural Differentiation ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cell ◽  
Induced Pluripotent

scholarly journals A Novel Feeder-Free Culture System for Human Pluripotent Stem Cell Culture and Induced Pluripotent Stem Cell Derivation

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e76205 ◽  
Author(s):  
Sanna Vuoristo ◽  
Sanna Toivonen ◽  
Jere Weltner ◽  
Milla Mikkola ◽  
Jarkko Ustinov ◽  
...  
Keyword(s):  
Cell Culture ◽  
Stem Cell ◽  
Culture System ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cell ◽  
Stem Cell Culture ◽  
Stem Cell Derivation ◽  
Induced Pluripotent

scholarly journals NKX3-1 is required for induced pluripotent stem cell reprogramming and can replace OCT4 in mouse and human iPSC induction

2018 ◽  
Vol 20 (8) ◽  
pp. 900-908 ◽  
Author(s):  
Thach Mai ◽  
Glenn J. Markov ◽  
Jennifer J. Brady ◽  
Adelaida Palla ◽  
Hong Zeng ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cell Reprogramming ◽  
Induced Pluripotent ◽  
Human Ipsc

scholarly journals Induced pluripotent stem cell-derived enteric neural crest cells repopulate human aganglionic tissue-engineered intestine to form key components of the enteric nervous system

2020 ◽  
Vol 11 ◽  
pp. 204173142090570 ◽  
Author(s):  
David F Chang ◽  
Samuel M Zuber ◽  
Elizabeth A Gilliam ◽  
Laura-Marie A Nucho ◽  
Gabriel Levin ◽  
...  
Keyword(s):  
Nervous System ◽  
Small Intestine ◽  
Stem Cell ◽  
Enteric Nervous System ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cell ◽  
Cell Therapies ◽  
Induced Pluripotent ◽  
Immunocompromised Mice

Models for enteric neuropathies, in which intestinal nerves are absent or injured, are required to evaluate possible cell therapies. However, existing options, including transgenic mice, are variable and fragile. Here immunocompromised mice were implanted with human pluripotent stem cell–derived tissue-engineered small intestine 10 weeks prior to a second survival surgery in which enteric nervous system precursor cells, or saline controls, were injected into the human intestinal organoid–derived tissue-engineered small intestine and analyzed 4 weeks later. Human intestinal organoid–derived tissue-engineered small intestine implants injected with saline as controls illustrated formation of intestinal epithelium and mesenchyme without an enteric nervous system. Second surgical introduction of human pluripotent stem cell–generated enteric nervous system precursors into developing human intestinal organoid–derived tissue-engineered small intestine implants resulted in proliferative migratory neuronal and glial cells, including multiple neuronal subtypes, and demonstrated function in contractility assays.

scholarly journals Honing the Double-Edged Sword: Improving Human iPSC-Microglia Models

2020 ◽  
Vol 11 ◽  
Author(s):  
Anne Hedegaard ◽  
Szymon Stodolak ◽  
William S. James ◽  
Sally A. Cowley
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Media Composition ◽  
Physiological Relevance ◽  
Key Features ◽  
Induced Pluripotent ◽  
Human Ipsc

Human induced Pluripotent Stem Cell (hiPSC) models are a valuable new tool for research into neurodegenerative diseases. Neuroinflammation is now recognized as a key process in neurodegenerative disease and aging, and microglia are central players in this. A plethora of hiPSC-derived microglial models have been published recently to explore neuroinflammation, ranging from monoculture through to xenotransplantation. However, combining physiological relevance, reproducibility, and scalability into one model is still a challenge. We examine key features of the in vitro microglial environment, especially media composition, extracellular matrix, and co-culture, to identify areas for improvement in current hiPSC-microglia models.

scholarly journals A near-infrared fluorescent voltage-sensitive dye allows for moderate-throughput electrophysiological analyses of human induced pluripotent stem cell-derived cardiomyocytes

2014 ◽  
Vol 307 (9) ◽  
pp. H1370-H1377 ◽  
Author(s):  
Angelica Lopez-Izquierdo ◽  
Mark Warren ◽  
Michael Riedel ◽  
Scott Cho ◽  
Shuping Lai ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Precision ◽  
Pluripotent Stem Cell ◽  
Near Infrared ◽  
Induced Pluripotent Stem Cell ◽  
Patch Clamp Technique ◽  
Voltage Sensitive Dye ◽  
Transmembrane Voltage ◽  
Induced Pluripotent ◽  
Human Ipsc

Human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM)-based assays are emerging as a promising tool for the in vitro preclinical screening of QT interval-prolonging side effects of drugs in development. A major impediment to the widespread use of human iPSC-CM assays is the low throughput of the currently available electrophysiological tools. To test the precision and applicability of the near-infrared fluorescent voltage-sensitive dye 1-(4-sulfanatobutyl)-4-{β[2-(di- n-butylamino)-6-naphthyl]butadienyl}quinolinium betaine (di-4-ANBDQBS) for moderate-throughput electrophysiological analyses, we compared simultaneous transmembrane voltage and optical action potential (AP) recordings in human iPSC-CM loaded with di-4-ANBDQBS. Optical AP recordings tracked transmembrane voltage with high precision, generating nearly identical values for AP duration (AP durations at 10%, 50%, and 90% repolarization). Human iPSC-CMs tolerated repeated laser exposure, with stable optical AP parameters recorded over a 30-min study period. Optical AP recordings appropriately tracked changes in repolarization induced by pharmacological manipulation. Finally, di-4-ANBDQBS allowed for moderate-throughput analyses, increasing throughput >10-fold over the traditional patch-clamp technique. We conclude that the voltage-sensitive dye di-4-ANBDQBS allows for high-precision optical AP measurements that markedly increase the throughput for electrophysiological characterization of human iPSC-CMs.

A microfluidic gradient device for drug screening with human iPSC-derived motoneurons

The Analyst ◽  
2020 ◽  
Vol 145 (8) ◽  
pp. 3081-3089 ◽  
Author(s):  
Sung Joon Mo ◽  
Ju-Hyun Lee ◽  
Hyeon Gi Kye ◽  
Jong Min Lee ◽  
Eun-Joong Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Drug Screening ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Screening System ◽  
Induced Pluripotent ◽  
Gradient Device ◽  
Human Ipsc

We developed a microfluidic gradient device to utilize as a drug screening system with human induced pluripotent stem cell (hiPSC)-derived motoneurons.

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