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Advanced Drug Delivery Reviews Jan 2016Regenerative medicine, including preclinical studies in large animal models and tissue engineering approaches as well as innovative assays for drug discovery, will... (Review)
Review
Regenerative medicine, including preclinical studies in large animal models and tissue engineering approaches as well as innovative assays for drug discovery, will require the constant supply of hPSC-derived cardiomyocytes and other functional progenies. Respective cell production processes must be robust, economically viable and ultimately GMP-compliant. Recent research has enabled transition of lab scale protocols for hPSC expansion and cardiomyogenic differentiation towards more controlled processing in industry-compatible culture platforms. Here, advanced strategies for the cultivation and differentiation of hPSCs will be reviewed by focusing on stirred bioreactor-based techniques for process upscaling. We will discuss how cardiomyocyte mass production might benefit from recent findings such as cell expansion at the cardiovascular progenitor state. Finally, remaining challenges will be highlighted, specifically regarding three dimensional (3D) hPSC suspension culture and critical safety issues ahead of clinical translation.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Humans; Myocytes, Cardiac; Pluripotent Stem Cells; Stem Cell Research; Tissue Engineering; Wnt Signaling Pathway
PubMed: 26658242
DOI: 10.1016/j.addr.2015.11.016 -
Journal of Laboratory Automation Dec 2013The survival, growth, self-renewal, and differentiation of human pluripotent stem cells (hPSCs) are influenced by their microenvironment, or so-called "niche,"... (Review)
Review
The survival, growth, self-renewal, and differentiation of human pluripotent stem cells (hPSCs) are influenced by their microenvironment, or so-called "niche," consisting of particular chemical and physical cues. Previous studies on mesenchymal stem cells and other stem cells have collectively uncovered the importance of physical cues and have begun to shed light on how stem cells sense and process such cues. In an attempt to support similar progress in mechanobiology of hPSCs, we review mechanosensory machinery, which plays an important role in cell-extracellular matrix interactions, cell-cell interactions, and subsequent intracellular responses. In addition, we review recent studies on the mechanobiology of hPSCs, in which engineered micromechanical environments were used to investigate effects of specific physical cues. Identifying key physical cues and understanding their mechanism will ultimately help in harnessing the full potential of hPSCs for clinical applications.
Topics: Biomechanical Phenomena; Biomedical Research; Biophysics; Humans; Pluripotent Stem Cells
PubMed: 24062363
DOI: 10.1177/2211068213503156 -
Journal of Cellular and Molecular... Nov 2013Human embryonic stem cells (hESCs) can be differentiated into structurally and electrically functional myocardial tissue and have the potential to regenerate large... (Review)
Review
Human embryonic stem cells (hESCs) can be differentiated into structurally and electrically functional myocardial tissue and have the potential to regenerate large regions of infarcted myocardium. One of the key challenges that needs to be addressed towards full-scale clinical application of hESCs is enhancing survival of the transplanted cells within ischaemic or scarred, avascular host tissue. Shortly after transplantation, most hESCs are lost as a result of multiple mechanical, cellular and host factors, and a large proportion of the remaining cells undergo apoptosis or necrosis shortly thereafter, as a result of loss of adhesion-related signals, ischaemia, inflammation or immunological rejection. Blocking the apoptotic signalling pathways of the cells, using pro-survival cocktails, conditioning hESCs prior to transplant, promoting angiogenesis, immunosuppressing the host and using of bioengineered matrices are among the emerging techniques that have been shown to optimize cell survival. This review presents an overview of the current strategies for optimizing cell and host tissue to improve the survival and efficacy of cardiac cells derived from pluripotent stem cells.
Topics: Animals; Cell Survival; Coronary Vessels; Embryonic Stem Cells; Graft Survival; Heart Diseases; Humans; Myocardium; Pluripotent Stem Cells; Regenerative Medicine
PubMed: 24118766
DOI: 10.1111/jcmm.12147 -
Current Opinion in Hematology Jul 2010Induced pluripotent stem cell (iPSC) technology, which uses defined transcription factors to reprogram somatic cells to become pluripotent cells, offers a significant... (Review)
Review
PURPOSE OF REVIEW
Induced pluripotent stem cell (iPSC) technology, which uses defined transcription factors to reprogram somatic cells to become pluripotent cells, offers a significant technical simplicity and enables generation of patient-specific pluripotent stem cells with reduced ethical concerns. This review will focus on recent progresses in understanding of iPSCs and improved methods of generating iPSCs.
RECENT FINDINGS
Whereas iPSCs generated from a variety of cell sources were found to be nearly identical functionally to embryonic stem cells, some differences were also identified and remain to be characterized. Meanwhile, new methods of generating iPSCs with minimal or no exogenous genetic modifications to cells have advanced rapidly.
SUMMARY
iPSC technology provides unprecedented opportunities in biomedical research and regenerative medicine. However, there remain a great deal to learn about iPSC safety, the reprogramming mechanisms, and better ways to direct a specific reprogramming process. The iPSC field will flourish on its mechanistic studies, iPSC-based disease modeling, and identification of new small molecules that modulate reprogramming.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Embryonic Stem Cells; Gene Transfer Techniques; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Transcription Factors
PubMed: 20442654
DOI: 10.1097/MOH.0b013e328339f2ee -
Cellular and Molecular Life Sciences :... Nov 2012Induced pluripotent stem (iPS) cells have attracted a great deal attention as a new pluripotent stem cell type that can be generated from somatic cells, such as... (Review)
Review
Induced pluripotent stem (iPS) cells have attracted a great deal attention as a new pluripotent stem cell type that can be generated from somatic cells, such as fibroblasts, by introducing the transcription factors Oct3/4, Sox2, Klf4, and c-Myc. The mechanism of generation, however, is not fully understood. Two mechanistic theories have been proposed; the stochastic model purports that every cell type has the potential to be reprogrammed to become an iPS cell and the elite model proposes that iPS cell generation occurs only from a subset of cells. Some reports have provided theoretical support for the stochastic model, but a recent publication demonstrated findings that support the elite model, and thus the mechanism of iPS cell generation remains under debate. To enhance our understanding of iPS cells, it is necessary to clarify the properties of the original cell source, i.e., the components of the original populations and the potential of each population to become iPS cells. In this review, we discuss the two theories and their implications in iPS cell research.
Topics: Adult Stem Cells; Animals; Cell Differentiation; Cell Line; Fibroblasts; Humans; Induced Pluripotent Stem Cells; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Mesenchymal Stem Cells; Mice; Models, Biological; Octamer Transcription Factor-3; Pluripotent Stem Cells; Proto-Oncogene Proteins c-myc; SOXB1 Transcription Factors
PubMed: 22527723
DOI: 10.1007/s00018-012-0994-5 -
Methods in Molecular Biology (Clifton,... 2023Dynamic pluripotent stem cell (PSC) states are in vitro adaptations of the pluripotency continuum in vivo. Previous studies have generated a number of PSCs with distinct...
Dynamic pluripotent stem cell (PSC) states are in vitro adaptations of the pluripotency continuum in vivo. Previous studies have generated a number of PSCs with distinct properties. By modulating the FGF, TGF-β, and WNT pathways, we have derived intermediate PSCs (FTW-PSCs) that are permissive for direct primordial germ cell-like cell (PGC-LC) induction in vitro. Here, we describe the method for derivation and maintenance of mouse and human FTW-PSCs, as well as PGC-LC induction from FTW-PSCs.
Topics: Humans; Pluripotent Stem Cells; Germ Cells; Cell Differentiation
PubMed: 37464248
DOI: 10.1007/978-1-0716-3259-8_16 -
Experimental Cell Research Oct 2020
Topics: Animals; Cell Differentiation; Embryonic Development; Humans; Pluripotent Stem Cells; Research
PubMed: 32540402
DOI: 10.1016/j.yexcr.2020.112147 -
Toxicology Dec 2010Despite considerable progress in modelling human liver toxicity, the requirement still exists for efficient, predictive and cost effective in vitro models to reduce... (Review)
Review
Despite considerable progress in modelling human liver toxicity, the requirement still exists for efficient, predictive and cost effective in vitro models to reduce attrition during drug development. Thousands of compounds fail in this process, with hepatotoxicity being one of the significant causes of failure. The cost of clinical studies is substantial, therefore it is essential that toxicological screening is performed early on in the drug development process. Human hepatocytes represent the gold standard model for evaluating drug toxicity, but are a limited resource. Current alternative models are based on immortalised cell lines and animal tissue, but these are limited by poor function, exhibit species variability and show instability in culture. Pluripotent stem cells are an attractive alternative as they are capable of self-renewal and differentiation to all three germ layers, and thereby represent a potentially inexhaustible source of somatic cells. The differentiation of human embryonic stem cells and induced pluripotent stem cells to functional hepatocyte like cells has recently been reported. Further development of this technology could lead to the scalable production of hepatocyte like cells for liver toxicity screening and clinical therapies. Additionally, induced pluripotent stem cell derived hepatocyte like cells may permit in vitro modelling of gene polymorphisms and genetic diseases.
Topics: Cell Differentiation; Cytotoxins; Hepatocytes; Humans; Liver; Models, Biological; Pluripotent Stem Cells; Toxicity Tests
PubMed: 20674645
DOI: 10.1016/j.tox.2010.07.012 -
Trends in Cardiovascular Medicine Feb 2021
Topics: Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Pluripotent Stem Cells
PubMed: 32276084
DOI: 10.1016/j.tcm.2020.03.006 -
Zhonghua Gan Zang Bing Za Zhi =... Mar 2022Liver is one of the most important organs in the human body. Liver diseases are also a major threat to human health and longevity. Hepatic decompensation treatment is...
Liver is one of the most important organs in the human body. Liver diseases are also a major threat to human health and longevity. Hepatic decompensation treatment is quite difficult due to multiple reasons. Extracorporeal liver support devices are unable to solve this problem, and there is a severe shortage of orthotopic liver transplant donors. Study of pluripotent stem cell-derived hepatocytes and organoids can determine not only hepatocyte fate, but also liver development, regeneration mechanisms, and pathophysiology. Furthermore, it can be used for drug screening in order to provide a stable source of functional hepatocytes for future transplantation therapy. Culture of pluripotent stem cell-derived hepatocytes and organoids has a self-organizing process similar to liver development, i.e., starting with changes in several key factors, and eventually forming functionally complex cells/organs. This paper introduces the main methods and progress of pluripotent stem cell-derived hepatocytes and organoids, with hope to provide clues for future research.
Topics: Cell Differentiation; Hepatocytes; Humans; Induced Pluripotent Stem Cells; Liver; Organoids; Pluripotent Stem Cells
PubMed: 35462478
DOI: 10.3760/cma.j.cn501113-20220318-00120