Evaluating the utility of cardiomyocytes from human pluripotent stem cells for drug screening

2010 ◽  
Vol 38 (4) ◽  
pp. 1037-1045 ◽  
Author(s):  
Emily Dick ◽  
Divya Rajamohan ◽  
Jonathon Ronksley ◽  
Chris Denning
Keyword(s):  
Stem Cells ◽  
Drug Screening ◽  
Pluripotent Stem Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Human Pluripotent Stem Cells ◽  
Attrition Rates ◽  
Human Cardiomyocytes ◽  
Induced Pluripotent

Functional cardiomyocytes can now be derived routinely from hPSCs (human pluripotent stem cells), which collectively include embryonic and induced pluripotent stem cells. This technology presents new opportunities to develop pharmacologically relevant in vitro screens to detect cardiotoxicity, with a view to improving patient safety while reducing the economic burden to industry arising from high drug attrition rates. In the present article, we consider the need for human cardiomyocytes in drug-screening campaigns and review the strategies used to differentiate hPSCs towards the cardiac lineage. During early stages of differentiation, hPSC-cardiomyocytes display gene expression profiles, ultra-structures, ion channel functionality and pharmacological responses reminiscent of an embryonic phenotype, but maturation during extended time in culture has been demonstrated convincingly. Notably, hPSC-cardiomyocytes have been shown to respond in a highly predictable manner to over 40 compounds that have a known pharmacological effect on the human heart. This suggests that further development and validation of the hPSC-cardiomyocyte model as a tool for assessing cardiotoxicity is warranted.

Mini Review; Differentiation of Human Pluripotent Stem Cells into Oocytes

2020 ◽  
Vol 15 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Gaifang Wang ◽  
Maryam Farzaneh
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cells ◽  
Human Oocyte ◽  
Differentiation Potential ◽  
Cell Lineages ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.

scholarly journals Monogenic Diabetes Modeling: In Vitro Pancreatic Differentiation From Human Pluripotent Stem Cells Gains Momentum

2021 ◽  
Vol 12 ◽  
Author(s):  
Juan Ignacio Burgos ◽  
Ludovic Vallier ◽  
Santiago A. Rodríguez-Seguí
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Single Gene ◽  
Cell Loss ◽  
Monogenic Diabetes ◽  
Human Pluripotent Stem Cells ◽  
Chronic Hyperglycemia ◽  
Disease Associated Genes ◽  
Induced Pluripotent

The occurrence of diabetes mellitus is characterized by pancreatic β cell loss and chronic hyperglycemia. While Type 1 and Type 2 diabetes are the most common types, rarer forms involve mutations affecting a single gene. This characteristic has made monogenic diabetes an interesting disease group to model in vitro using human pluripotent stem cells (hPSCs). By altering the genotype of the original hPSCs or by deriving human induced pluripotent stem cells (hiPSCs) from patients with monogenic diabetes, changes in the outcome of the in vitro differentiation protocol can be analyzed in detail to infer the regulatory mechanisms affected by the disease-associated genes. This approach has been so far applied to a diversity of genes/diseases and uncovered new mechanisms. The focus of the present review is to discuss the latest findings obtained by modeling monogenic diabetes using hPSC-derived pancreatic cells generated in vitro. We will specifically focus on the interpretation of these studies, the advantages and limitations of the models used, and the future perspectives for improvement.

scholarly journals Single-Cell Gene Expression Profiles Define Self-Renewing, Pluripotent, and Lineage Primed States of Human Pluripotent Stem Cells

2014 ◽  
Vol 2 (6) ◽  
pp. 881-895 ◽  
Author(s):  
Shelley R. Hough ◽  
Matthew Thornton ◽  
Elizabeth Mason ◽  
Jessica C. Mar ◽  
Christine A. Wells ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Single Cell ◽  
Pluripotent Stem Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Human Pluripotent Stem Cells ◽  
Cell Gene Expression ◽  
Cell Gene

scholarly journals Effect of Small Molecular Compounds on Properties of Fibroblast in Chuan Snub-nosed Monkey

2021 ◽  
Author(s):  
juanjuan wang ◽  
xin liu ◽  
jing yang ◽  
hanxing guo ◽  
jingjing li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Cell Morphology ◽  
Pluripotent Stem Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Compound ◽  
Donor Cells ◽  
Induced Pluripotent ◽  
Molecular Compounds

Abstract Small molecular compounds could improve the induction efficiency of induced pluripotent stem cells (iPS). To investigate their effects on the efficiency of interspecies nuclear transfers, fibroblasts from the Chuan snub-nosed monkey were treated with small molecular compounds and used as donor cells to be injected into the enucleated oocytes of a goat. The gene expression profiles in the cell-constructed embryos, with and without the small molecular compound treatments, were determined by qPCR. Results showed that the cell morphology showed obvious changes, while the gene expression profiles of the fibroblasts were altered by the treatment. The pluripotent genes (Oct4, sox2, and nanog) were significantly increased on treatment with the small molecular compounds. Results demonstrated that these small molecular compounds could alter the properties of the donor cells, to promote the expression levels of the pluripotent genes for the Chuan golden-goat interspecies embryo, which would provide references for conservation of Chuan snub-nosed monkey.

Abstract P418: Transcriptomic And Genomic DNA Accessibility Dynamics During Differentiation Of Induced Pluripotent Stem Cells Derived Smooth Muscle Cells And Acquisition Of Contractile Phenotype

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
LU LIU ◽  
Adrien Georges ◽  
Nabila Bouatia-Naji
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Contractile Function ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Human Aorta ◽  
Rna Seq ◽  
Dna Accessibility ◽  
Induced Pluripotent

Introduction: Smooth muscle cells (SMCs) capacity to phenotype switching between proliferative and quiescent (contractile) is a widely studied mechanism in cardiovascular disease. Primary SMCs tend to lose many physiological features in culture, which makes the study of their contractile function challenging. Recently, an optimized protocol of induced pluripotent stem cells (iPSCs) differentiation into contractile SMCs was described. Here we aimed at defining the transcriptomic and open chromatin dynamics during the acquisition of SMCs phenotypes. Methods: We differentiated 4 human iPSC lines (2 males, 2 females) towards either contractile (Repsox induced) or synthetic (PDGF-BB/TGF-β induced) SMC phenotypes using a 24-days protocol. We performed RNA-Seq and assay for transposase accessible chromatin (ATAC)-Seq at 5 time points of differentiation. We analyzed gene expression profiles and compared them to existing dataset of human aorta by principle component analyses (PCA) and gene set enrichment analyses using GO terms. Results: iPSCs derived SMCs showed expected morphology and positive expression of SMC markers. Synthetic SMCs (SSMCs) exhibited greater capacity of proliferation, migration and lower calcium release capacity, compared to contractile SMCs (CSMCs). RNA-Seq results showed that multiple genes involved in the contractile function of arteries, including myosin light chain kinase (MYLK) and angiotensin type 1 receptor ( AGTR1 ) genes were highly expressed in CSMCs compared to SSMCs. Overall, CSMCs conserved SMC properties beyond 24 days and their gene expression profile clustered near human aorta. During late differentiation stages, CSMCs showed an upregulation of genes involved in cardiovascular system development, whereas genes involved in cell stress were upregulated in SSMCs. Conclusions: We describe global genomic profiles of iPSCs derived CSMCs that presented comparable gene expression profiles to mature artery tissue. Combination with upcoming DNA accessibility maps is expected to allow the functional exploration of genetic risk variation involved in several arterial diseases involving the impairment of the SMCs contractile function.

Human Pluripotent Stem Cells and Drug Discovery: A New Beginning

2016 ◽  
Vol 1 (1) ◽  
pp. 27
Author(s):  
Vinod Verma ◽  
A. Mehta ◽  
S.J.S. Flora
Keyword(s):  
Stem Cells ◽  
Drug Discovery ◽  
Pluripotent Stem Cells ◽  
Cost Effective ◽  
Cell Types ◽  
In Vitro Models ◽  
Human Pluripotent Stem Cells ◽  
Specific Cell ◽  
Attrition Rates

Human pluripotent stem cells (hPSCs) offer unique opportunities to discover and develop a new generation of drugs. Their ability to differentiate into virtually any cell type renders them a cost-effective, renewable source of tissue-specific cell types capable of predicting human responses towards novel chemical entities. Using these improved in vitro models based on physiologically relevant human cell types could result in identifying highly precise and safe compounds, thereby reducing drug attrition rates. Moreover, ability to develop humanised disease models for patient-stratified drug screening makes hPSCs an impeccable tool in translational medicine. In this mini-review we focus on the positives and negatives of utilising hPSC-derived cell types as drug discovery platforms with special emphasis on cardio-, hepato- and embryotoxicity.

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