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Stem Cells Translational Medicine May 2014Because of recent advances, the array of human pluripotent stem cells now contains embryonic stem cells, derived from "surplus" in vitro fertilization embryos or from... (Review)
Review
Because of recent advances, the array of human pluripotent stem cells now contains embryonic stem cells, derived from "surplus" in vitro fertilization embryos or from cloned embryos; induced pluripotent stem cells; and amniotic fluid stem cells. Here, we compare these stem cell types regarding ethical and legal concerns, cultivation conditions, genomic stability, tumor developing potentials, and applicability for disease modeling and human therapy. This overview highlights that in the future appropriate methodological management must include a decision on the "optimal" stem cell to use before the specific application.
Topics: Amniotic Fluid; Bioethical Issues; Embryonic Stem Cells; Genomic Instability; Humans; Induced Pluripotent Stem Cells; Stem Cell Transplantation
PubMed: 24692589
DOI: 10.5966/sctm.2013-0194 -
Stem Cell Reports Dec 2018Nicotinamide, the amide form of vitamin B3, is widely used in disease treatments and stem cell applications. However, nicotinamide's impact often cannot be attributed to...
Nicotinamide, the amide form of vitamin B3, is widely used in disease treatments and stem cell applications. However, nicotinamide's impact often cannot be attributed to its nutritional functions. In a vitamin screen, we find that nicotinamide promotes cell survival and differentiation in human pluripotent stem cells. Nicotinamide inhibits the phosphorylation of myosin light chain, suppresses actomyosin contraction, and leads to improved cell survival after individualization. Further analysis demonstrates that nicotinamide is an inhibitor of multiple kinases, including ROCK and casein kinase 1. We demonstrate that nicotinamide affects human embryonic stem cell pluripotency and differentiation as a selective kinase inhibitor. The findings in this report may help researchers design better strategies to develop nicotinamide-related stem cell applications and disease treatments.
Topics: Actomyosin; Casein Kinase I; Cell Differentiation; Cell Survival; Human Embryonic Stem Cells; Humans; NAD; Niacinamide; Pluripotent Stem Cells; Protein Kinase Inhibitors; rho-Associated Kinases
PubMed: 30503259
DOI: 10.1016/j.stemcr.2018.10.023 -
Protein & Cell Jan 2012While human induced pluripotent stem cells (hiPSCs) have promising applications in regenerative medicine, most of the hiPSC lines available today are not suitable for...
While human induced pluripotent stem cells (hiPSCs) have promising applications in regenerative medicine, most of the hiPSC lines available today are not suitable for clinical applications due to contamination with nonhuman materials, such as sialic acid, and potential pathogens from animal-product-containing cell culture systems. Although several xeno-free cell culture systems have been established recently, their use of human fibroblasts as feeders reduces the clinical potential of hiPSCs due to batch-to-batch variation in the feeders and time-consuming preparation processes. In this study, we have developed a xeno-free and feeder-cell-free human embryonic stem cell (hESC)/hiPSC culture system using human plasma and human placenta extracts. The system maintains the self-renewing capacity and pluripotency of hESCs for more than 40 passages. Human iPSCs were also derived from human dermal fibroblasts using this culture system by overexpressing three transcription factors-Oct4, Sox2 and Nanog. The culture system developed here is inexpensive and suitable for large scale production.
Topics: Cell Culture Techniques; Cell Differentiation; Cellular Reprogramming; Culture Media; Extracellular Matrix Proteins; Female; Fibroblasts; Humans; Lentivirus; Placenta; Pluripotent Stem Cells; Pregnancy; Sodium Chloride; Transcription Factors
PubMed: 22259120
DOI: 10.1007/s13238-012-2002-0 -
Stem Cells (Dayton, Ohio) Jan 2012Adult stem cell therapies have provided success for more than 50 years, through reconstitution of the hematopoietic system using bone marrow, umbilical cord blood, and... (Review)
Review
Adult stem cell therapies have provided success for more than 50 years, through reconstitution of the hematopoietic system using bone marrow, umbilical cord blood, and mobilized peripheral blood transplantation. Mesenchymal stem cell (MSC)-mediated therapy is a fast-growing field that has proven safe and effective in the treatment of various degenerative diseases and tissue injuries. Since the first derivation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), there has been impressive progress toward developing safe clinical applications from PSCs. Recent successes in transgene-free iPSC reprogramming have brought attention to the potential of clinical applications of these pluripotent cells, but key hurdles must be overcome, which are discussed in this review. Looking to the future, it could be advantageous to derive MSC from iPSC or human ESC in cases where genetic engineering is needed, since in the PSCs, clones with "safe harbor" vector integration could be selected, expanded, and differentiated. Here, we describe the status of the progress of the use of MSC and PSCs in clinical trials and analyze the challenges that should be overcome before iPSC-derived MSC therapy can be used widely in the clinic.
Topics: Adult Stem Cells; Animals; Cell Differentiation; Cellular Reprogramming; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cells; Mice; Pluripotent Stem Cells; Stem Cell Transplantation; Transgenes
PubMed: 21898694
DOI: 10.1002/stem.727 -
Experimental Cell Research Apr 2020Both embryo-derived (ESC) and induced pluripotent stem cell (iPSC) lines have been established in rabbit. They exhibit the essential characteristics of primed... (Review)
Review
Both embryo-derived (ESC) and induced pluripotent stem cell (iPSC) lines have been established in rabbit. They exhibit the essential characteristics of primed pluripotency. In this review, we described their characteristic features at both molecular and functional levels. We also described the attempts to reprogram rabbit pluripotent stem cells (rbPSCs) toward the naive state of pluripotency using methods established previously to capture this state in rodents and primates. In the last section, we described and discussed our current knowledge of rabbit embryo development pertaining to the mechanisms of early lineage segregation. We argued that the molecular signature of naive-state pluripotency differs between mice and rabbits. We finally discussed some of the key issues to be addressed for capturing the naive state in rbPSCs, including the generation of embryo/PSC chimeras.
Topics: Animals; Cell Differentiation; Chimera; Embryo, Mammalian; Embryonic Development; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Induced Pluripotent Stem Cells; Rabbits
PubMed: 32057751
DOI: 10.1016/j.yexcr.2020.111908 -
Circulation Research Jan 2014The discovery of human pluripotent stem cells (hPSCs), including both human embryonic stem cells and human-induced pluripotent stem cells, has opened up novel paths for... (Review)
Review
The discovery of human pluripotent stem cells (hPSCs), including both human embryonic stem cells and human-induced pluripotent stem cells, has opened up novel paths for a wide range of scientific studies. The capability to direct the differentiation of hPSCs into functional cardiomyocytes has provided a platform for regenerative medicine, development, tissue engineering, disease modeling, and drug toxicity testing. Despite exciting progress, achieving the optimal benefits has been hampered by the immature nature of these cardiomyocytes. Cardiac maturation has long been studied in vivo using animal models; however, finding ways to mature hPSC cardiomyocytes is only in its initial stages. In this review, we discuss progress in promoting the maturation of the hPSC cardiomyocytes, in the context of our current knowledge of developmental cardiac maturation and in relation to in vitro model systems such as rodent ventricular myocytes. Promising approaches that have begun to be examined in hPSC cardiomyocytes include long-term culturing, 3-dimensional tissue engineering, mechanical loading, electric stimulation, modulation of substrate stiffness, and treatment with neurohormonal factors. Future studies will benefit from the combinatorial use of different approaches that more closely mimic nature's diverse cues, which may result in broader changes in structure, function, and therapeutic applicability.
Topics: Animals; Cell Differentiation; Cell Engineering; Cells, Cultured; Genetic Engineering; Humans; Induced Pluripotent Stem Cells; Models, Animal; Myocytes, Cardiac; Pluripotent Stem Cells; Time Factors
PubMed: 24481842
DOI: 10.1161/CIRCRESAHA.114.300558 -
Cell Transplantation 2012Stem cells are self-renewable cells with the differentiation capacity to develop into somatic cells with biological functions. This ability to sustain a renewable source... (Review)
Review
Stem cells are self-renewable cells with the differentiation capacity to develop into somatic cells with biological functions. This ability to sustain a renewable source of multi- and/or pluripotential differentiation has brought new hope to the field of regenerative medicine in terms of cell therapy and tissue engineering. Moreover, stem cells are invaluable tools as in vitro models for studying diverse fields, from basic scientific questions such as developmental processes and lineage commitment, to practical application including drug screening and testing. The stem cells with widest differentiation potential are pluripotent stem cells (PSCs), which are rare cells with the ability to generate somatic cells from all three germ layers. PSCs are considered the most optimal choice for therapeutic potential of stem cells, bringing new impetus to the field of regenerative medicine. In this article, we discuss the therapeutic potential of human PSCs (hPSCs) including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), reviewing the current preclinical and clinical data using these stem cells. We describe the classification of different sources of hPSCs, ongoing research, and currently encountered clinical obstacles of these novel and versatile human stem cells.
Topics: Cell Differentiation; Cell- and Tissue-Based Therapy; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Regenerative Medicine; Tissue Engineering
PubMed: 22449556
DOI: 10.3727/096368911X627507 -
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 -
Viruses Jul 2015The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs), which has revolutionized the approaches to study... (Review)
Review
The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs), which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host-pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.
Topics: Animals; Antiviral Agents; Humans; Induced Pluripotent Stem Cells; Models, Biological; Virus Diseases; Virus Physiological Phenomena; Viruses
PubMed: 26184286
DOI: 10.3390/v7072800 -
Molecular Pharmaceutics Oct 2011Heart diseases are a leading cause of mortality worldwide. Terminally differentiated adult cardiomyocytes (CMs) lack the innate ability to regenerate. Their malfunction... (Review)
Review
Heart diseases are a leading cause of mortality worldwide. Terminally differentiated adult cardiomyocytes (CMs) lack the innate ability to regenerate. Their malfunction or significant loss can lead to conditions from cardiac arrhythmias to heart failure. For myocardial repair, cell- and gene-based therapies offer promising alternatives to donor organ transplantation. Human embryonic stem cells (hESCs) can self-renew while maintaining their pluripotency. Direct reprogramming of adult somatic cells to become pluripotent hES-like cells (also known as induced pluripotent stem cells or iPSCs) has been achieved. Both hESCs and iPSCs have been successfully differentiated into genuine human CMs. In this review, we describe our current knowledge of the structure-function properties of hESC/iPSC-CMs, with an emphasis on their electrophysiology and Ca(2+) handling, along with the hurdles faced and potential solutions for translating into clinical and other applications (e.g., disease modeling, cardiotoxicity and drug screening).
Topics: Animals; Electrophysiological Phenomena; Embryonic Stem Cells; Heart; Humans; Induced Pluripotent Stem Cells; MicroRNAs; Muscle Development; Myocardial Infarction; Myocytes, Cardiac; Pluripotent Stem Cells; Regeneration; Sinoatrial Node; Tissue Engineering
PubMed: 21879736
DOI: 10.1021/mp2002363