Hypothalamic contribution to pituitary functions is recapitulated in vitro using 3D-cultured human iPS cells

2020 ◽  
Author(s):  
Kasai T ◽  
Suga H ◽  
Sakakibara   ◽  
Ozone C ◽  
Matsumoto R ◽  
...  
Keyword(s):  
Ips Cells ◽  
Human Ips Cells

In Vitro Differentiation of Human iPS Cells into Neural like Cells on a Biomimetic Polyurea

2016 ◽  
Vol 54 (1) ◽  
pp. 601-607 ◽  
Author(s):  
Elham Hoveizi ◽  
Somayeh Ebrahimi-Barough ◽  
Shima Tavakol ◽  
Khadije Sanamiri
Keyword(s):  
Ips Cells ◽  
In Vitro Differentiation ◽  
Human Ips Cells

Generation of Blood Cells from Human Ips Cells in Vitro through the Hematopoietic Progenitors Concentrated within the Unique Structures, Ips-Sac.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1992-1992 ◽  
Author(s):  
Naoya Takayama ◽  
Koji Eto ◽  
Hiromitsu Nakauchi ◽  
Shinya Yamanaka
Keyword(s):  
Cell Lines ◽  
Blood Cells ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Dermal Fibroblasts ◽  
Hematopoietic Progenitors ◽  
Transfusion Therapy ◽  
Ips Cell ◽  
Human Ips Cells

Abstract Human embryonic stem cells (hESCs) are proposed as an alternative source for transfusion therapy or studies of hematopoiesis. We have recently established an in vitro culture system whereby hESCs can be differentiated into hematopoietic progenitors within the ‘unique sac-like structures’ (ES-sacs), that are able to produce megakaryocytes and platelets (Takayama et al., Blood, 111, 5298–306, 2008). However there is a little concern that repetitive transfusion with same human ESC-derived platelets may induce immunological rejection against transfused platelets expressing allogenic HLA. Meanwhile, induced pluripotent stem (iPS) cells established from donor with identical HLA are well known as a potential and given source on platelet transfusion devoid of rejection. To examine if human iPS cells could generate platelets as well as from hESCs, we utilized 3 different human iPS cell lines; two were induced by transduction of 4 genes (Oct3/4, Klf4, Sox2, and c-Myc) in adult dermal fibroblasts, and one was by 3 genes without c-Myc. Sac-like structures (iPS-sac), inducible from 3 iPS cell lines, concentrated hematopoietic progenitors that expressed early hemato-endothelial markers, such as CD34, CD31, CD41a (integrin αIIb) and CD45. These progenitors were able to form hematopoietic colonies in semi-solid culture and differentiate into several blood cells including leukocytes, erythrocytes or platelets. Of these, obtained platelets responded to agonist stimulation, in which the function was as much as human ESC-derived platelets, as evidenced by PAC-1 binding with activated αIIbβ3 integrin or full spreading onto fibrinogen. These results collectively indicated that human dermal fibroblasts could generate functional and mature hematopoietic cells through the reprogramming process and this method may be useful for basic studies of hematopoietic disorders and clinical therapy in the future.

scholarly journals Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells

2021 ◽  
Author(s):  
Emi Sano ◽  
Ayaka Sakamoto ◽  
Natsumi Mimura ◽  
Ai Hirabayashi ◽  
Yukiko Muramoto ◽  
...  
Keyword(s):  
Individual Differences ◽  
Es Cells ◽  
Membrane Vesicles ◽  
Ips Cells ◽  
Genetic Differences ◽  
Progeny Virus ◽  
Double Membrane ◽  
Human Ips Cells ◽  
Induced Pluripotent

AbstractGenetic differences are a primary reason for differences in the susceptibility and severity of coronavirus disease 2019 (COVID-19). Because induced pluripotent stem (iPS) cells maintain the genetic information of the donor, they can be used to model individual differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vitro. Notably, undifferentiated human iPS cells themselves cannot be infected bySARS-CoV-2. Using adenovirus vectors, here we found that human iPS cells expressing the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) (ACE2-iPS cells) can be infected with SARS-CoV-2. In infected ACE2-iPS cells, the expression of SARS-CoV-2 nucleocapsid protein, the budding of viral particles, the production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We also evaluated COVID-19 therapeutic drugs in ACE2-iPS cells and confirmed the strong antiviral effects of Remdesivir, EIDD-2801, and interferon-beta. In addition, we performed SARS-CoV-2 infection experiments on ACE2-iPS/ES cells from 8 individuals. Male iPS/ES cells were more capable of producing the virus as compared with female iPS/ES cells. These findings suggest that ACE2-iPS cells can not only reproduce individual differences in SARS-CoV-2 infection in vitro, but they are also a useful resource to clarify the causes of individual differences in COVID-19 due to genetic differences.Graphical Abstract

scholarly journals Efficient and Reproducible Myogenic Differentiation from Human iPS Cells: Prospects for Modeling Miyoshi Myopathy In Vitro

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e61540 ◽  
Author(s):  
Akihito Tanaka ◽  
Knut Woltjen ◽  
Katsuya Miyake ◽  
Akitsu Hotta ◽  
Makoto Ikeya ◽  
...  
Keyword(s):  
Myogenic Differentiation ◽  
Ips Cells ◽  
Human Ips Cells ◽  
Miyoshi Myopathy

Approach to Neurotoxicity using Human iPSC Neurons: Consortium for Safety Assessment using Human iPS Cells

2020 ◽  
Vol 21 (9) ◽  
pp. 780-786
Author(s):  
Takafumi Shirakawa ◽  
Ikuro Suzuki
Keyword(s):  
Cell Biology ◽  
Safety Assessment ◽  
Neuronal Cell ◽  
Electrode Array ◽  
Ips Cells ◽  
Current Status ◽  
Ips Cell ◽  
Human Ips Cells

Neurotoxicity, as well as cardiotoxicity and hepatotoxicity, resulting from administration of a test article is considered a major adverse effect both pre-clinically and clinically. Among the different types of neurotoxicity occurring during the drug development process, seizure is one of the most serious one. Seizure occurrence is usually assessed using in vivo animal models, the Functional Observational Battery, the Irwin test or electroencephalograms. In in vitro studies, a number of assessments can be performed using animal organs/cells. Interestingly, recent developments in stem cell biology, especially the development of Human-Induced Pluripotent Stem (iPS) cells, are enabling the assessment of neurotoxicity in human iPS cell-derived neurons. Further, a Multi-Electrode Array (MEA) using rodent neurons is a useful tool for identifying seizure-inducing compounds. The Consortium for Safety Assessment using Human iPS Cells (CSAHi; http://csahi.org/en/) was established in 2013 by the Japan Pharmaceutical Manufacturers Association (JPMA) to verify the application of human iPS cell-derived neuronal cells to drug safety evaluation. The Neuro Team of CSAHi has been attempting to evaluate the seizure risk of compounds using the MEA platform. Here, we review the current status of neurotoxicity and recent work, including problems related to the use of the MEA assay with human iPS neuronal cell-derived neurons, and future developments.

Comprehensive Cardiac Safety Assessment using hiPS-cardiomyocytes (Consortium for Safety Assessment using Human iPS Cells: CSAHi)

2020 ◽  
Vol 21 (9) ◽  
pp. 829-841
Author(s):  
Kiyoshi Takasuna ◽  
Katsuyuki Kazusa ◽  
Tomohiro Hayakawa
Keyword(s):  
Safety Assessment ◽  
Ips Cells ◽  
Heart Team ◽  
Motion Field ◽  
Cardiac Safety ◽  
Drug Induced ◽  
Diverse Range ◽  
Advantages And Disadvantages ◽  
Human Ips Cells

Current cardiac safety assessment platforms (in vitro hERG-centric, APD, and/or in vivo animal QT assays) are not fully predictive of drug-induced Torsades de Pointes (TdP) and do not address other mechanism-based arrhythmia, including ventricular tachycardia or ventricular fibrillation, or cardiac safety liabilities such as contractile and structural cardiotoxicity which are another growing safety concerns. We organized the Consortium for Safety Assessment using Human iPS cells (CSAHi; http://csahi.org/en/) in 2013, based on the Japan Pharmaceutical Manufacturers Association (JPMA), to verify the application of human iPS/ES cell-derived cardiomyocytes for drug safety evaluation. The CSAHi HEART team focused on comprehensive screening strategies to predict a diverse range of cardiotoxicities using recently introduced platforms such as the Multi-Electrode Array (MEA), cellular impedance, Motion Field Imaging (MFI), and optical imaging of Ca transient to identify strengths and weaknesses of each platform. Our study showed that hiPS-CMs used in these platforms could detect pharmacological responses that were more relevant to humans compared to existing hERG, APD, or Langendorff (MAPD/contraction) assays. Further, MEA and other methods such as impedance, MFI, and Ca transient assays provided paradigm changes of platforms for predicting drug-induced QT risk and/or arrhythmia or contractile dysfunctions. In contrast, since discordances such as overestimation (false positive) of arrhythmogenicity, oversight, or opposite conclusions in positive inotropic and negative chronotropic activities to some compounds were also confirmed, possibly due to their functional immaturity of hiPS-CMs, hiPS-CMs should be used in these platforms for cardiac safety assessment based upon their advantages and disadvantages.

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