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Integrative Biology : Quantitative... Sep 2018Birth defects are a common occurrence in the United States and worldwide. Currently, evaluation of potential developmental toxicants (i.e., teratogens) relies heavily on... (Review)
Review
Birth defects are a common occurrence in the United States and worldwide. Currently, evaluation of potential developmental toxicants (i.e., teratogens) relies heavily on animal-based models which do not always adequately mimic human development. In order to address this, researchers are developing in vitro human-based models which utilize human pluripotent stem cells (hPSCs) to assess the teratogenic potential of chemical substances. The field of human developmental toxicity assays includes a variety of platforms including monolayer, micropattern, embryoid body, and 3D organoid cultures. In this review, we will overview the field of human teratogenic assays, detail the most recent advances, and discuss current limitations and future perspectives.
Topics: Animals; Cell Differentiation; Cell Movement; Cell Proliferation; Embryo Culture Techniques; Embryoid Bodies; Embryonic Stem Cells; Gene Expression Regulation; Humans; Pluripotent Stem Cells; Teratogens; Toxicity Tests
PubMed: 30095839
DOI: 10.1039/c8ib00082d -
BMB Reports Dec 2015Pluripotent stem cells only exist in a narrow window during early embryonic development, whereas multipotent stem cells are abundant throughout embryonic development and... (Review)
Review
Pluripotent stem cells only exist in a narrow window during early embryonic development, whereas multipotent stem cells are abundant throughout embryonic development and are retained in various adult tissues and organs. While pluripotent stem cell lines have been established from several species, including mouse, rat, and human, it is still challenging to establish stable multipotent stem cell lines from embryonic or adult tissues. Based on current knowledge, we anticipate that by manipulating extrinsic and intrinsic signaling pathways, most if not all types of stem cells can be maintained in a long-term culture. In this article, we summarize current culture conditions established for the long-term maintenance of authentic pluripotent and multipotent stem cells and the signaling pathways involved. We also discuss the general principles of stem cell maintenance and propose several strategies on the establishment of novel stem cell lines through manipulation of signaling pathways.
Topics: Animals; Cell Culture Techniques; Cell Line; Cell Self Renewal; Embryonic Stem Cells; Humans; Multipotent Stem Cells; Pluripotent Stem Cells; Signal Transduction
PubMed: 26497581
DOI: 10.5483/bmbrep.2015.48.12.215 -
International Journal of Molecular... Feb 2024Pluripotent stem cells (PSCs) can differentiate into three germ layers and diverse autologous cell lines. Since cattle are the most commonly used large domesticated... (Review)
Review
Pluripotent stem cells (PSCs) can differentiate into three germ layers and diverse autologous cell lines. Since cattle are the most commonly used large domesticated animals, an important food source, and bioreactors, great efforts have been made to establish bovine PSCs (bPSCs). bPSCs have great potential in bovine breeding and reproduction, modeling in vitro differentiation, imitating cancer development, and modeling diseases. Currently, bPSCs mainly include bovine embryonic stem cells (bESCs), bovine induced pluripotent stem cells (biPSCs), and bovine expanded potential stem cells (bEPSCs). Establishing stable bPSCs in vitro is a critical scientific challenge, and researchers have made numerous efforts to this end. In this review, the category of PSC pluripotency; the establishment of bESCs, biPSCs, and bEPSCs and its challenges; and the application outlook of bPSCs are discussed, aiming to provide references for future research.
Topics: Cattle; Animals; Pluripotent Stem Cells; Cell Differentiation; Induced Pluripotent Stem Cells; Embryonic Stem Cells
PubMed: 38396797
DOI: 10.3390/ijms25042120 -
Stem Cell Reviews and Reports Feb 2015Recent advances on human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) have brought us closer... (Review)
Review
Recent advances on human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) have brought us closer to the realization of their clinical potential. Nonetheless, tissue engineering and regenerative medicine applications will require the generation of hPSC products well beyond the laboratory scale. This also mandates the production of hPSC therapeutics in fully-defined, xeno-free systems and in a reproducible manner. Toward this goal, we summarize current developments in defined media free of animal-derived components for hPSC culture. Bioinspired and synthetic extracellular matrices for the attachment, growth and differentiation of hPSCs are also reviewed. Given that most progress in xeno-free medium and substrate development has been demonstrated in two-dimensional rather than three dimensional culture systems, translation from the former to the latter poses unique difficulties. These challenges are discussed in the context of cultivation platforms of hPSCs as aggregates, on microcarriers or after encapsulation in biocompatible scaffolds.
Topics: Animals; Cell Culture Techniques; Cell Proliferation; Cellular Microenvironment; Embryonic Stem Cells; Extracellular Matrix; Humans; Induced Pluripotent Stem Cells; Models, Biological; Pluripotent Stem Cells
PubMed: 25077810
DOI: 10.1007/s12015-014-9544-x -
Stem Cell Reports Aug 2023The Human Pluripotent Stem Cell Registry established a database of clinical studies using human pluripotent stem cells (PSCs) as starting material for cell therapies.... (Review)
Review
The Human Pluripotent Stem Cell Registry established a database of clinical studies using human pluripotent stem cells (PSCs) as starting material for cell therapies. Since 2018, we have observed a switch toward human induced pluripotent stem cells (iPSCs) from human embryonic stem cells. However, rather than using iPSCs for personalized medicines, allogeneic approaches dominate. Most treatments target ophthalmopathies, and genetically modified iPSCs are used to generate tailored cells. We observe a lack of standardization and transparency about the PSCs lines used, characterization of the PSC-derived cells, and the preclinical models and assays applied to show efficacy and safety.
Topics: Humans; Induced Pluripotent Stem Cells; Cell Differentiation; Pluripotent Stem Cells; Human Embryonic Stem Cells; Cell- and Tissue-Based Therapy
PubMed: 37028422
DOI: 10.1016/j.stemcr.2023.03.005 -
Current Cardiology Reports Apr 2018The goal of this review is to highlight the potential of induced pluripotent stem cell (iPSC)-based modeling as a tool for studying human cardiovascular diseases. We... (Review)
Review
PURPOSE OF REVIEW
The goal of this review is to highlight the potential of induced pluripotent stem cell (iPSC)-based modeling as a tool for studying human cardiovascular diseases. We present some of the current cardiovascular disease models utilizing genome editing and patient-derived iPSCs.
RECENT FINDINGS
The incorporation of genome-editing and iPSC technologies provides an innovative research platform, providing novel insight into human cardiovascular disease at molecular, cellular, and functional level. In addition, genome editing in diseased iPSC lines holds potential for personalized regenerative therapies. The study of human cardiovascular disease has been revolutionized by cellular reprogramming and genome editing discoveries. These exceptional technologies provide an opportunity to generate human cell cardiovascular disease models and enable therapeutic strategy development in a dish. We anticipate these technologies to improve our understanding of cardiovascular disease pathophysiology leading to optimal treatment for heart diseases in the future.
Topics: Cardiovascular Diseases; Cell Differentiation; Gene Editing; Humans; Induced Pluripotent Stem Cells; Models, Biological; Precision Medicine
PubMed: 29666931
DOI: 10.1007/s11886-018-0984-9 -
Stem Cells Translational Medicine Sep 2023Recently, 2 branches of the wide area of synthetic biology-in vitro gametogenesis and synthetic embryo development-have gained considerable attention. Rodent induced...
Recently, 2 branches of the wide area of synthetic biology-in vitro gametogenesis and synthetic embryo development-have gained considerable attention. Rodent induced pluripotent stem cells derived via reprogramming of somatic cells can in vitro be differentiated into gametes to produce fertile offspring. And even synthetic embryos with organ progenitors were generated ex utero entirely from murine pluripotent stem cells. The use of these approaches in basic research, which is rightfully accompanied by an ethical discussion, will allow hitherto unattainable insights into the processes of the beginning of life. There is a broad international consensus that currently the application of these technologies in human-assisted reproduction must be considered to be unsafe and unethical. However, newspaper headlines also addressed the putatively resulting paradigm shift in human reproduction and thereby raised expectations in patients. Due to unsolved biological and technological obstacles, most scientists do not anticipate translation of any of these approaches into human reproductive medicine, if ever, for the next 10 years. Still, whereas the usage of synthetic embryos for reproductive purposes should be banned, in the context of in vitro-derived human gametes it is not too early to initiate the evaluation of the ethical implications, which could still remain assuming all technological hurdles can ever be cleared.
Topics: Humans; Animals; Mice; Pluripotent Stem Cells; Germ Cells; Gametogenesis; Cell Differentiation; Induced Pluripotent Stem Cells
PubMed: 37471266
DOI: 10.1093/stcltm/szad042 -
Cell Transplantation 2023Cell expansion of human pluripotent stem cells (hPSCs) commonly depends on Matrigel as a coating matrix on two-dimensional (2D) culture plates and 3D microcarriers....
Cell expansion of human pluripotent stem cells (hPSCs) commonly depends on Matrigel as a coating matrix on two-dimensional (2D) culture plates and 3D microcarriers. However, the xenogenic Matrigel requires sophisticated quality-assurance processes to meet clinical requirements. In this study, we develop an innovative coating-free medium for expanding hPSCs. The xenofree medium supports the weekend-free culture and competitive growth of hPSCs on several cell culture plastics without an additional pre-coating process. The pluripotent stemness of the expanded cells is stably sustained for more than 10 passages, featured with high pluripotent marker expressions, normal karyotyping, and differentiating capacity for three germ layers. The expression levels of some integrins are reduced, compared with those of the hPSCs on Matrigel. This medium also successfully supports the clonal expansion and induced pluripotent stem cell establishment from mitochondrial-defective MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) patient's peripheral blood mononuclear cells. This innovative hPSC medium provides a straightforward scale-up process for producing clinical-orientated hPSCs by excluding the conventional coating procedure.
Topics: Humans; Induced Pluripotent Stem Cells; Leukocytes, Mononuclear; Pluripotent Stem Cells; Cell Culture Techniques; Cell Differentiation
PubMed: 37698258
DOI: 10.1177/09636897231198172 -
Cells Dec 2021Human pluripotent stem cell (hPSC)-derived neuron cultures have emerged as models of electrical activity in the human brain. Microelectrode arrays (MEAs) measure changes... (Review)
Review
Human pluripotent stem cell (hPSC)-derived neuron cultures have emerged as models of electrical activity in the human brain. Microelectrode arrays (MEAs) measure changes in the extracellular electric potential of cell cultures or tissues and enable the recording of neuronal network activity. MEAs have been applied to both human subjects and hPSC-derived brain models. Here, we review the literature on the functional characterization of hPSC-derived two- and three-dimensional brain models with MEAs and examine their network function in physiological and pathological contexts. We also summarize MEA results from the human brain and compare them to the literature on MEA recordings of hPSC-derived brain models. MEA recordings have shown network activity in two-dimensional hPSC-derived brain models that is comparable to the human brain and revealed pathology-associated changes in disease models. Three-dimensional hPSC-derived models such as brain organoids possess a more relevant microenvironment, tissue architecture and potential for modeling the network activity with more complexity than two-dimensional models. hPSC-derived brain models recapitulate many aspects of network function in the human brain and provide valid disease models, but certain advancements in differentiation methods, bioengineering and available MEA technology are needed for these approaches to reach their full potential.
Topics: Brain; Humans; Microelectrodes; Models, Biological; Neurons; Organoids; Pluripotent Stem Cells
PubMed: 35011667
DOI: 10.3390/cells11010106 -
Brain Research May 2016With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)"... (Review)
Review
With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what's wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control and to complement the iPSC-based approach for ALS disease modeling studies. Much knowledge has been generated from the study of both ALS iPSCs and ESCs. As these methods have advantages and disadvantages that should be balanced on experimental design in order for them to complement one another, combining the diverse methods would help build an expanded knowledge of ALS pathophysiology. The goals are to reverse engineer the human disease using ESCs and iPSCs, generate lineage reporter lines and in vitro disease models, target disease related genes, in order to better understand the molecular and cellular mechanisms of differentiation regulation along neural (neuronal versus glial) lineages, to unravel the pathogenesis of the neurodegenerative disease, and to provide appropriate cell sources for replacement therapy. This article is part of a Special Issue entitled SI: PSC and the brain.
Topics: Amyotrophic Lateral Sclerosis; Animals; Cellular Reprogramming; Humans; Induced Pluripotent Stem Cells; Motor Neurons; Neurodegenerative Diseases; Pluripotent Stem Cells; Stem Cell Transplantation
PubMed: 26423934
DOI: 10.1016/j.brainres.2015.09.023