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Cellular and Molecular Life Sciences :... Oct 2017Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to... (Review)
Review
Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to understand human heart disease and discover therapeutic targets that may lead to new compounds for clinical use. Current literature clearly shows that hPSC-CMs recapitulate many molecular, cellular, and functional aspects of human heart pathophysiology and their responses to cardioactive drugs. Here, we provide a comprehensive overview of hPSC-CMs models that have been described to date and highlight their most recent and remarkable contributions to research on cardiovascular diseases and disorders with cardiac traits. We conclude discussing immediate challenges, limitations, and emerging solutions.
Topics: Calcium; Cell Differentiation; Heart Diseases; Humans; Metabolome; Mitochondria; Mutation; Myocytes, Cardiac; Pluripotent Stem Cells; Sarcomeres
PubMed: 28573431
DOI: 10.1007/s00018-017-2546-5 -
Current Cardiology Reports May 2022Exciting pre-clinical data presents pluripotent stem cell-derived cardiomyocytes (PSC-CM) as a novel therapeutic prospect following myocardial infarction, and worldwide... (Review)
Review
PURPOSE OF REVIEW
Exciting pre-clinical data presents pluripotent stem cell-derived cardiomyocytes (PSC-CM) as a novel therapeutic prospect following myocardial infarction, and worldwide clinical trials are imminent. However, despite notable advances, several challenges remain. Here, we review PSC-CM pre-clinical studies, identifying key translational hurdles. We further discuss cell production and characterization strategies, identifying markers that may help generate cells which overcome these barriers.
RECENT FINDINGS
PSC-CMs can robustly repopulate infarcted myocardium with functional, force generating cardiomyocytes. However, current differentiation protocols produce immature and heterogenous cardiomyocytes, creating related issues such as arrhythmogenicity, immunogenicity and poor engraftment. Recent efforts have enhanced our understanding of cardiovascular developmental biology. This knowledge may help implement novel differentiation or gene editing strategies that could overcome these limitations. PSC-CMs are an exciting therapeutic prospect. Despite substantial recent advances, limitations of the technology remain. However, with our continued and increasing biological understanding, these issues are addressable, with several worldwide clinical trials anticipated in the coming years.
Topics: Cell Differentiation; Cell- and Tissue-Based Therapy; Humans; Induced Pluripotent Stem Cells; Myocardium; Myocytes, Cardiac; Pluripotent Stem Cells
PubMed: 35275365
DOI: 10.1007/s11886-022-01666-9 -
Experimental & Molecular Medicine Oct 2022Each cell in the human body has a distinguishable fate. Pluripotent stem cells are challenged with a myriad of lineage differentiation options. Defects are more likely... (Review)
Review
Each cell in the human body has a distinguishable fate. Pluripotent stem cells are challenged with a myriad of lineage differentiation options. Defects are more likely to be fatal to stem cells than to somatic cells due to the broad impact of the former on early development. Hence, a detailed understanding of the mechanisms that determine the fate of stem cells is needed. The mechanisms by which human pluripotent stem cells, although not fully equipped with complex chromatin structures or epigenetic regulatory mechanisms, accurately control gene expression and are important to the stem cell field. In this review, we examine the events driving pluripotent stem cell fate and the underlying changes in gene expression during early development. In addition, we highlight the role played by the epitranscriptome in the regulation of gene expression that is necessary for each fate-related event.
Topics: Humans; Gene Expression Regulation, Developmental; Pluripotent Stem Cells; Cell Differentiation; Epigenesis, Genetic; Cell Lineage
PubMed: 36266446
DOI: 10.1038/s12276-022-00824-x -
Cellular and Molecular Life Sciences :... Oct 2018Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNRPDGFRαKDR mesoderm in human pluripotent stem cell... (Review)
Review
Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNRPDGFRαKDR mesoderm in human pluripotent stem cell cultures. MBs are identified based on their capacity to form FGF2-dependent compact spheroid colonies in a serum-free semisolid medium. MBs colonies are composed of PDGFRβCD271EMCNDLK1CD73 primitive mesenchymal cells which are generated through endothelial/angioblastic intermediates (cores) formed during first 3-4 days of clonogenic cultures. MB-derived primitive mesenchymal cells have potential to differentiate into mesenchymal stromal/stem cells (MSCs), pericytes, and smooth muscle cells. In this review, we summarize the specification and developmental potential of MBs, emphasize features that distinguish MBs from other mesenchymal progenitors described in the literature and discuss the value of these findings for identifying molecular pathways leading to MSC and vasculogenic cell specification, and developing cellular therapies using MB-derived progeny.
Topics: Autoimmune Diseases; Cell Lineage; Embryonic Development; Endothelial Cells; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mesoderm; Pluripotent Stem Cells; Spheroids, Cellular
PubMed: 29992471
DOI: 10.1007/s00018-018-2871-3 -
The FEBS Journal Jun 2022The study of human evolution, long constrained by a lack of experimental model systems, has been transformed by the emergence of the induced pluripotent stem cell (iPSC)... (Review)
Review
The study of human evolution, long constrained by a lack of experimental model systems, has been transformed by the emergence of the induced pluripotent stem cell (iPSC) field. iPSCs can be readily established from noninvasive tissue sources, from both humans and other primates; they can be maintained in the laboratory indefinitely, and they can be differentiated into other tissue types. These qualities mean that iPSCs are rapidly becoming established as viable and powerful model systems with which it is possible to address questions in human evolution that were until now logistically and ethically intractable, especially in the quest to understand humans' place among the great apes, and the genetic basis of human uniqueness. In this review, we discuss the key lessons and takeaways of this nascent field; from the types of research, iPSCs make possible to lingering challenges and likely future directions. We provide a comprehensive overview of how the seemingly unlikely combination of iPSCs and explicit evolutionary frameworks is transforming what is possible in our understanding of humanity's past and present.
Topics: Animals; Cell Differentiation; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Primates
PubMed: 33876573
DOI: 10.1111/febs.15885 -
Stem Cells (Dayton, Ohio) Nov 2015Naïve or ground state pluripotency is a cellular state in vitro which resembles cells of the preimplantation epiblast in vivo. This state was first observed in mouse... (Review)
Review
Naïve or ground state pluripotency is a cellular state in vitro which resembles cells of the preimplantation epiblast in vivo. This state was first observed in mouse embryonic stem cells and is characterized by high rates of proliferation, the ability to differentiate widely, and global hypomethylation. Human pluripotent stem cells (hPSCs) correspond to a later or "primed" stage of embryonic development. The conversion of hPSCs to a naïve state is desirable as their features should facilitate techniques such as gene editing and more efficient differentiation. Here we review protocols which now allow derivation of naïve human pluripotent stem cells by transgene expression or the use of media formulations containing inhibitors and growth factors and correlate this with pathways involved. Maintenance of these ground state cells is possible using a combination of basic fibroblast growth factor and human leukemia inhibitory factor together with dual inhibition of glycogen synthase kinase 3 beta, and mitogen-activated protein kinase kinase (MEK). Close similarity between the ground state hPSC and the in vivo preimplantation epiblast have been shown both by demonstrating similar upregulation of endogenous retroviruses and correlation of global RNA-seq data. This suggests that the human naïve state is not an in vitro artifact.
Topics: Animals; Cell Differentiation; Embryonic Development; Embryonic Stem Cells; Humans; Pluripotent Stem Cells; Signal Transduction
PubMed: 26119873
DOI: 10.1002/stem.2085 -
Progress in Neurobiology Sep 2018Human pluripotent stem cell (PSC) technology and direct somatic cell reprogramming have opened up a promising new avenue in the field of neuroscience. These recent... (Review)
Review
Human pluripotent stem cell (PSC) technology and direct somatic cell reprogramming have opened up a promising new avenue in the field of neuroscience. These recent advances allow researchers to obtain virtually any cell type found in the human brain, making it possible to produce and study functional neurons in laboratory conditions for both scientific and medical purposes. Although distinct approaches have shown to be successful in directing neuronal cell fate in vitro, their refinement and optimization, as well as the search for alternative approaches, remains necessary to help realize the full potential of the eventually derived neuronal populations. Furthermore, we are currently limited in the number of neuronal subtypes whose induction is fully established, and different cultivation protocols for each subtype exist, making it challenging to increase the reproducibility and decrease the variances that are observed between different protocols. In this review, we summarize the progress that has been made in generating various neuronal subtypes from PSCs and somatic cells, with special emphasis on chemically defined systems, transcription factor-mediated reprogramming and epigenetic-based approaches. We also discuss the efforts that are being made to increase the efficiency of current protocols and address the potential for the use of these cells in disease modelling, drug discovery and regenerative medicine.
Topics: Animals; Cell Differentiation; Cellular Reprogramming; Epigenomics; In Vitro Techniques; Neurons; Pluripotent Stem Cells; Transcription Factors
PubMed: 29653249
DOI: 10.1016/j.pneurobio.2018.04.003 -
International Journal of Molecular... Jul 2021Organoids represent one of the most important advancements in the field of stem cells during the past decade. They are three-dimensional in vitro culturing models that... (Review)
Review
Organoids represent one of the most important advancements in the field of stem cells during the past decade. They are three-dimensional in vitro culturing models that originate from self-organizing stem cells and can mimic the in vivo structural and functional specificities of body organs. Organoids have been established from multiple adult tissues as well as pluripotent stem cells and have recently become a powerful tool for studying development and diseases in vitro, drug screening, and host-microbe interaction. The use of stem cells-that have self-renewal capacity to proliferate and differentiate into specialized cell types-for organoids culturing represents a major advancement in biomedical research. Indeed, this new technology has a great potential to be used in a multitude of fields, including cancer research, hereditary and infectious diseases. Nevertheless, organoid culturing is still rife with many challenges, not limited to being costly and time consuming, having variable rates of efficiency in generation and maintenance, genetic stability, and clinical applications. In this review, we aim to provide a synopsis of pluripotent stem cell-derived organoids and their use for disease modeling and other clinical applications.
Topics: Animals; Drug Evaluation, Preclinical; Humans; Models, Biological; Organ Culture Techniques; Organoids; Pluripotent Stem Cells
PubMed: 34299287
DOI: 10.3390/ijms22147667 -
International Journal of Molecular... Aug 2019Astrocytes play vital roles in neurological disorders. The use of human induced pluripotent stem cell (iPSC)-derived astrocytes provides a chance to explore the... (Review)
Review
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.
Topics: Animals; Astrocytes; Biomarkers; Cell Differentiation; Disease Susceptibility; Humans; Induced Pluripotent Stem Cells; Models, Biological; Nervous System Diseases; Neuroglia; Phenotype; Pluripotent Stem Cells
PubMed: 31398826
DOI: 10.3390/ijms20163862 -
Stem Cell Reports Dec 2020Higher-order chromatin structure is tightly linked to gene expression and therefore cell identity. In recent years, the chromatin landscape of pluripotent stem cells has... (Review)
Review
Higher-order chromatin structure is tightly linked to gene expression and therefore cell identity. In recent years, the chromatin landscape of pluripotent stem cells has become better characterized, and unique features at various architectural levels have been revealed. However, the mechanisms that govern establishment and maintenance of these topological characteristics and the temporal and functional relationships with transcriptional or epigenetic features are still areas of intense study. Here, we will discuss progress and limitations of our current understanding regarding how the 3D chromatin topology of pluripotent stem cells is established during somatic cell reprogramming and maintained during cell division. We will also discuss evidence and theories about the driving forces of topological reorganization and the functional links with key features and properties of pluripotent stem cell identity.
Topics: Animals; Cell Division; Cellular Reprogramming; Chromatin; Chromatin Assembly and Disassembly; Humans; Pluripotent Stem Cells
PubMed: 33242398
DOI: 10.1016/j.stemcr.2020.10.012