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International Journal of Molecular... Nov 2014Stem cells harbor significant potential for regenerative medicine as well as basic and clinical translational research. Prior to harnessing their reparative nature for... (Review)
Review
Stem cells harbor significant potential for regenerative medicine as well as basic and clinical translational research. Prior to harnessing their reparative nature for degenerative diseases, concerns regarding their genetic integrity and mutation acquisition need to be addressed. Here we review pluripotent and multipotent stem cell response to DNA damage including differences in DNA repair kinetics, specific repair pathways (homologous recombination vs. non-homologous end joining), and apoptotic sensitivity. We also describe DNA damage and repair strategies during reprogramming and discuss potential genotoxic agents that can reduce the inherent risk for teratoma formation and mutation accumulation. Ensuring genomic stability in stem cell lines is required to achieve the quality control standards for safe clinical application.
Topics: Animals; Apoptosis; Cellular Reprogramming; DNA Damage; DNA Repair; Genomic Instability; Humans; Induced Pluripotent Stem Cells; Multipotent Stem Cells; Pluripotent Stem Cells; Stem Cells
PubMed: 25405730
DOI: 10.3390/ijms151120948 -
Stem Cells and Development Sep 2017Recent advancements in the ability to construct three-dimensional (3D) tissues and organoids from stem cells and biomaterials have not only opened abundant new research... (Review)
Review
Recent advancements in the ability to construct three-dimensional (3D) tissues and organoids from stem cells and biomaterials have not only opened abundant new research avenues in disease modeling and regenerative medicine but also have ignited investigation into important aspects of molecular diffusion in 3D cellular architectures. This article describes fundamental mechanics of diffusion with equations for modeling these dynamic processes under a variety of scenarios in 3D cellular tissue constructs. The effects of these diffusion processes and resultant concentration gradients are described in the context of the major molecular signaling pathways in stem cells that both mediate and are influenced by gas and nutrient concentrations, including how diffusion phenomena can affect stem cell state, cell differentiation, and metabolic states of the cell. The application of these diffusion models and pathways is of vital importance for future studies of developmental processes, disease modeling, and tissue regeneration.
Topics: Animals; Cell Communication; Cell Differentiation; Cell Proliferation; Diffusion; Humans; Models, Theoretical; Signal Transduction; Stem Cells; Tissue Engineering
PubMed: 28707964
DOI: 10.1089/scd.2017.0066 -
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 -
Cell Mar 2014Cell differentiation is an essential process for the development, growth, reproduction, and longevity of all multicellular organisms, and its regulation has been the... (Review)
Review
Cell differentiation is an essential process for the development, growth, reproduction, and longevity of all multicellular organisms, and its regulation has been the focus of intense investigation for the past four decades. The study of natural and induced stem cells has ushered an age of re-examination of what it means to be a stem or a differentiated cell. Past and recent discoveries in plants and animals, as well as novel experimental manipulations, are beginning to erode many of these established concepts and are forcing a re-evaluation of the experimental systems and paradigms presently being used to explore these and other biological process.
Topics: Animals; Biological Evolution; Cell Differentiation; Humans; Plant Cells; Plants; Pluripotent Stem Cells; Regeneration; Stem Cells
PubMed: 24679530
DOI: 10.1016/j.cell.2014.02.041 -
Cell May 2018
Topics: Animals; Cell Differentiation; Ethics, Research; Gene Editing; Humans; Models, Biological; Stem Cells; Tissue Engineering
PubMed: 29775587
DOI: 10.1016/j.cell.2018.05.010 -
Stem Cell Research & Therapy Jun 2013Pluripotent stem cells, both embryonic stem cells and induced pluripotent stem cells, are undifferentiated cells that can self-renew and potentially differentiate into... (Review)
Review
Pluripotent stem cells, both embryonic stem cells and induced pluripotent stem cells, are undifferentiated cells that can self-renew and potentially differentiate into all hematopoietic lineages, such as hematopoietic stem cells (HSCs), hematopoietic progenitor cells and mature hematopoietic cells in the presence of a suitable culture system. Establishment of pluripotent stem cells provides a comprehensive model to study early hematopoietic development and has emerged as a powerful research tool to explore regenerative medicine. Nowadays, HSC transplantation and hematopoietic cell transfusion have successfully cured some patients, especially in malignant hematological diseases. Owing to a shortage of donors and a limited number of the cells, hematopoietic cell induction from pluripotent stem cells has been regarded as an alternative source of HSCs and mature hematopoietic cells for intended therapeutic purposes. Pluripotent stem cells are therefore extensively utilized to facilitate better understanding in hematopoietic development by recapitulating embryonic development in vivo, in which efficient strategies can be easily designed and deployed for the generation of hematopoietic lineages in vitro. We hereby review the current progress of hematopoietic cell induction from embryonic stem/induced pluripotent stem cells.
Topics: Animals; Cell Differentiation; Cell Lineage; Embryoid Bodies; Embryonic Stem Cells; Hematopoietic Stem Cells; Humans; Induced Pluripotent Stem Cells; Models, Animal; Regenerative Medicine
PubMed: 23796405
DOI: 10.1186/scrt222 -
BioMed Research International 2013Stem cells possess huge importance in developmental biology, disease modelling, cell replacement therapy, and tissue engineering in regenerative medicine because they... (Review)
Review
Stem cells possess huge importance in developmental biology, disease modelling, cell replacement therapy, and tissue engineering in regenerative medicine because they have the remarkable potential for self-renewal and to differentiate into almost all the cell types in the human body. Elucidation of molecular mechanisms regulating stem cell potency and differentiation is essential and critical for extensive application. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are modular proteins consisting of RNA-binding motifs and auxiliary domains characterized by extensive and divergent functions in nucleic acid metabolism. Multiple roles of hnRNPs in transcriptional and posttranscriptional regulation enable them to be effective gene expression regulators. More recent findings show that hnRNP proteins are crucial factors implicated in maintenance of stem cell self-renewal and pluripotency and cell differentiation. The hnRNPs interact with certain sequences in target gene promoter regions to initiate transcription. In addition, they recognize 3'UTR or 5'UTR of specific gene mRNA forming mRNP complex to regulate mRNA stability and translation. Both of these regulatory pathways lead to modulation of gene expression that is associated with stem cell proliferation, cell cycle control, pluripotency, and committed differentiation.
Topics: Cell Differentiation; Cell Proliferation; Heterogeneous-Nuclear Ribonucleoproteins; Humans; Myocytes, Smooth Muscle; Neural Stem Cells; Stem Cells
PubMed: 23984388
DOI: 10.1155/2013/623978 -
Developmental Dynamics : An Official... Jul 2016During human development, pluripotency is present only in early stages of development. This ephemeral cell potential can be captured in vitro by obtaining pluripotent... (Review)
Review
During human development, pluripotency is present only in early stages of development. This ephemeral cell potential can be captured in vitro by obtaining pluripotent stem cells (PSC) with self-renewal properties, the human embryonic stem cells (hESC). However, diverse studies suggest the existence of a plethora of human PSC (hPSC) that can be derived from both embryonic and somatic sources, depending on defined culture conditions, their spatial origin, and the genetic engineering used for reprogramming. This review will focus on hPSC, covering the conventional primed hESC, naïve-like hPSC that resemble the ground-state of development, region-selective PSC, and human induced PSC (hiPSC). We will analyze differences and similarities in their differentiation potential as well as in the molecular circuitry of pluripotency. Finally, we describe the need for human feeder cells to derive and maintain hPSC, because they could emulate the interaction of in vivo pluripotent cells with extraembryonic structures that support development. Developmental Dynamics 245:762-773, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Cell Differentiation; Embryonic Stem Cells; Humans; Octamer Transcription Factor-3; Pluripotent Stem Cells
PubMed: 27004967
DOI: 10.1002/dvdy.24405 -
The Indian Journal of Medical Research Jun 2012All organisms depend on stem cells for their survival. As a result, stem cells may be a prerequisite for the evolution of specific characteristics in organisms that... (Review)
Review
All organisms depend on stem cells for their survival. As a result, stem cells may be a prerequisite for the evolution of specific characteristics in organisms that include regeneration, multicellularity and coloniality. Stem cells have attracted the attention of biologists and medical scientists for a long time. These provide materials for regenerative medicine. We review in this paper, the link between modern stem cell research and early studies in ancient organisms. It also outlines details on stem cells in the light of evolution with an emphasis on their regeneration potential, coloniality and multicellularity. The information provided might be of use to molecular biologists, medical scientists and developmental biologists who are engaged in integrated research involving the stem cells.
Topics: Animals; Biological Evolution; Gene Regulatory Networks; Humans; Mammals; Regenerative Medicine; Selection, Genetic; Stem Cells
PubMed: 22825600
DOI: No ID Found -
Biotechnology Progress 2009Stem cells have the ability for prolonged self-renewal and differentiation into mature cells of various lineages, which makes them important cell sources for tissue... (Review)
Review
Stem cells have the ability for prolonged self-renewal and differentiation into mature cells of various lineages, which makes them important cell sources for tissue engineering applications. Their remarkable ability to replenish and differentiate in vivo is regulated by both intrinsic and extrinsic cellular mechanisms. The anatomical location where the stem cells reside, known as the "stem cell niche or microenvironment," provides signals conducive to the maintenance of definitive stem cell properties. Physiological condition including oxygen tension is an important component of the stem cell microenvironment and has been shown to play a role in regulating both embryonic and adult stem cells. This review focuses on oxygen as a signaling molecule and the way it regulates the stem cells' development into mesenchymal tissues in vitro. The physiological relevance of low oxygen tension as an environmental parameter that uniquely benefits stem cells' expansion and maintenance is described along with recent findings on the regulatory effects of oxygen on embryonic stem cells and adult mesenchymal stem cells. The relevance to tissue engineering is discussed in the context of the need to specifically regulate the oxygen content in the cellular microenvironment in order to optimize in vitro tissue development.
Topics: Animals; Cell Hypoxia; Embryonic Stem Cells; Humans; Mesenchymal Stem Cells; Models, Biological; Signal Transduction; Stem Cells; Tissue Engineering
PubMed: 19198002
DOI: 10.1002/btpr.128