Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging.

Marrow stem cell lines from old donors and those from young controls gave equally rapid rates of colony growth on spleens of irradiated mice. Old and young stem cell lines competed equally well with chromosomally marked marrow stem cells from a young donor in producing cell types that are stimulated by bleeding; old cells competed 70% as well as young in producing cell types stimulated by phytohemagglutinin (PHA) in vitro. After a single serial transplantation, the rates of colony growth declined 1.5- to 2.5-fold, and the ability to compete declined 2- to 4-fold for bleeding-stimulated and 4- to 10-fold for PHA-stimulated cells. Thus, immediate stem cell proliferative capacities decline much more after one serial transplantation than after a lifetime of normal function.

Download Full-text

Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2014.0365 ◽

2015 ◽

Vol 370 (1680) ◽

pp. 20140365 ◽

Cited By ~ 19

Author(s):

Maria Rostovskaya ◽

Nicholas Bredenkamp ◽

Austin Smith

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Lines ◽

Pluripotent Stem Cells ◽

Pluripotent Stem Cell ◽

Human Pluripotent Stem Cells ◽

Type I ◽

Pancreatic Progenitors ◽

Stem Cell Lines

Human pluripotent stem cells can in principle be used as a source of any differentiated cell type for disease modelling, drug screening, toxicology testing or cell replacement therapy. Type I diabetes is considered a major target for stem cell applications due to the shortage of primary human beta cells. Several protocols have been reported for generating pancreatic progenitors by in vitro differentiation of human pluripotent stem cells. Here we first assessed one of these protocols on a panel of pluripotent stem cell lines for capacity to engender glucose sensitive insulin-producing cells after engraftment in immunocompromised mice. We observed variable outcomes with only one cell line showing a low level of glucose response. We, therefore, undertook a systematic comparison of different methods for inducing definitive endoderm and subsequently pancreatic differentiation. Of several protocols tested, we identified a combined approach that robustly generated pancreatic progenitors in vitro from both embryo-derived and induced pluripotent stem cells. These findings suggest that, although there are intrinsic differences in lineage specification propensity between pluripotent stem cell lines, optimal differentiation procedures may consistently direct a substantial fraction of cells into pancreatic specification.

Download Full-text

Epigenetic regulation in stem cell development, cell fate conversion, and reprogramming

BioMolecular Concepts ◽

10.1515/bmc-2014-0036 ◽

2015 ◽

Vol 6 (1) ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Kazuyuki Ohbo ◽

Shin-ichi Tomizawa

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Transcription Factors ◽

Cell Fate ◽

Cell Lines ◽

Cell Fate Decisions ◽

Micro Rnas ◽

Stem Cell Lines ◽

Cell Fate Conversion

AbstractStem cells are identified classically by an in vivo transplantation assay plus additional characterization, such as marker analysis, linage-tracing and in vitro/ex vivo differentiation assays. Stem cell lines have been derived, in vitro, from adult tissues, the inner cell mass (ICM), epiblast, and male germ stem cells, providing intriguing insight into stem cell biology, plasticity, heterogeneity, metastable state, and the pivotal point at which stem cells irreversibly differentiate to non-stem cells. During the past decade, strategies for manipulating cell fate have revolutionized our understanding about the basic concept of cell differentiation: stem cell lines can be established by introducing transcription factors, as with the case for iPSCs, revealing some of the molecular interplay of key factors during the course of phenotypic changes. In addition to de-differentiation approaches for establishing stem cells, another method has been developed whereby induced expression of certain transcription factors and/or micro RNAs artificially converts differentiated cells from one committed lineage to another; notably, these cells need not transit through a stem/progenitor state. The molecular cues guiding such cell fate conversion and reprogramming remain largely unknown. As differentiation and de-differentiation are directly linked to epigenetic changes, we overview cell fate decisions, and associated gene and epigenetic regulations.

Download Full-text

Embryos, Clones, and Stem Cells: A Scientific Primer

The Scientific World JOURNAL ◽

10.1100/tsw.2004.121 ◽

2004 ◽

Vol 4 ◽

pp. 662-715 ◽

Cited By ~ 3

Author(s):

Kenyon S. Tweedell

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Embryonic Stem Cells ◽

Cell Lines ◽

Human Embryonic Stem Cells ◽

Adult Stem Cells ◽

Embryonic Stem ◽

Normal Function ◽

Cell Recovery ◽

Stem Cell Lines

This article is intended to give the nonspecialist an insight into the nuances of “clones”, cloning, and stem cells. It distinguishes embryonic and adult stem cells, their normal function in the organism, their origin, and how they are recovered to produce stem cell lines in culture. As background, the fundamental processes of embryo development are reviewed and defined, since the manipulation of stem cell lines into desired specialized cells employs many of the same events. Stem cells are defined and characterized and shown how they function in the intact organism during early development and later during cell regeneration in the adult. The complexity of stem cell recovery and their manipulation into specific cells and tissue is illustrated by reviewing current experimentation on both embryonic and adult stem cells in animals and limited research on human stem cell lines. The current and projected use of stem cells for human diseases and repair, along with the expanding methodology for the recovery of human embryonic stem cells, is described. An assessment on the use of human embryonic stem cells is considered from ethical, legal, religious, and political viewpoints.

Download Full-text

Patentability of the Human Embryonic Stem Cell Lines: A Legal and Ethical Aspect

10.5772/intechopen.94483 ◽

2020 ◽

Author(s):

Tansu Sayar Kanyış ◽

Ezgi Arslan ◽

Oğuzhan Kanyış

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Embryonic Stem Cell ◽

Cell Lines ◽

Human Embryo ◽

Human Embryonic Stem Cell ◽

Embryonic Stem ◽

Point Of View ◽

Stem Cell Lines

In this study, patentability of the human embryonic stem cell lines has discussed in the legal and ethical perspectives. In vitro human embryonic stem cells can be defined as body parts that are departed from the body. Human embryonic stem cell lines are constituted of differentiated self-renewal pluripotent stem cells, which means they have no characteristics to become a human-being. However, interpreting the terms like human embryo and right to property widely can cause the human embryonic stem cell lines are misunderstood as unpatentable. For our point of view, giving the human embryo the protections of both personal rights of the donor and the right to property of the owner of the invention does not reduce the legal/moral status of the human embryo. Besides, the obligations which these rights imposes to their owners, such as the principle of human dignity and prohibition of financial gain can protect the human embryo in a better way.

Download Full-text

Generation and characterization of stable pig pregastrulation epiblast stem cell lines

Cell Research ◽

10.1038/s41422-021-00592-9 ◽

2021 ◽

Author(s):

Minglei Zhi ◽

Jinying Zhang ◽

Qianzi Tang ◽

Dawei Yu ◽

Shuai Gao ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Lines ◽

Pluripotent Stem Cells ◽

Large Scale ◽

Biological Research ◽

Marker Genes ◽

Stem Cell Lines ◽

Cloned Gene

AbstractPig epiblast-derived pluripotent stem cells are considered to have great potential and broad prospects for human therapeutic model development and livestock breeding. Despite ongoing attempts since the 1990s, no stably defined pig epiblast-derived stem cell line has been established. Here, guided by insights from a large-scale single-cell transcriptome analysis of pig embryos from embryonic day (E) 0 to E14, specifically, the tracing of pluripotency changes during epiblast development, we developed an in vitro culture medium for establishing and maintaining stable pluripotent stem cell lines from pig E10 pregastrulation epiblasts (pgEpiSCs). Enabled by chemical inhibition of WNT-related signaling in combination with growth factors in the FGF/ERK, JAK/STAT3, and Activin/Nodal pathways, pgEpiSCs maintain their pluripotency transcriptome features, similar to those of E10 epiblast cells, and normal karyotypes after more than 240 passages and have the potential to differentiate into three germ layers. Strikingly, ultradeep in situ Hi-C analysis revealed functional impacts of chromatin 3D-spatial associations on the transcriptional regulation of pluripotency marker genes in pgEpiSCs. In practice, we confirmed that pgEpiSCs readily tolerate at least three rounds of successive gene editing and generated cloned gene-edited live piglets. Our findings deliver on the long-anticipated promise of pig pluripotent stem cells and open new avenues for biological research, animal husbandry, and regenerative biomedicine.

Download Full-text

The embryonic stem cell test (EST), an in vitro embryotoxicity test using two permanent mouse cell lines: 3T3 fibroblasts and embryonic stem cells

Ersatz- und Ergänzungsmethoden zu Tierversuchen - Forschung ohne Tierversuche 1997 ◽

10.1007/978-3-7091-7500-2_69 ◽

1998 ◽

pp. 289-290 ◽

Cited By ~ 4

Author(s):

H. Spielmann ◽

I. Pohl ◽

B. Döring ◽

M. Liebsch ◽

F. Moldenhauer

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Embryonic Stem Cells ◽

Embryonic Stem Cell ◽

Cell Lines ◽

Embryonic Stem ◽

Mouse Cell ◽

3T3 Fibroblasts ◽

Cell Test

Download Full-text

OP0073 ESTABLISHMENT OF HUMAN INDUCED PLURIPOTENT STEM CELL-LINES (IPSC) FOR IN VITRO MODELLING HAND OSTHEOARTHRITIS

10.1136/annrheumdis-2019-eular.2793 ◽

2019 ◽

Author(s):

Rocío Castro-Viñuelas ◽

Clara Sanjurjo-Rodríguez ◽

María Piñeiro-Ramil ◽

Tamara Hermida Gómez ◽

Isaac Fuentes-Boquete ◽

...

Keyword(s):

Stem Cell ◽

Cell Lines ◽

Pluripotent Stem Cell ◽

Induced Pluripotent Stem Cell ◽

Stem Cell Lines ◽

Induced Pluripotent ◽

In Vitro Modelling

Download Full-text

Ex Uno Plures: Molecular Designs for Embryonic Pluripotency

Physiological Reviews ◽

10.1152/physrev.00001.2014 ◽

2015 ◽

Vol 95 (1) ◽

pp. 245-295 ◽

Cited By ~ 19

Author(s):

Kyle M. Loh ◽

Bing Lim ◽

Lay Teng Ang

Keyword(s):

Stem Cell ◽

Transcription Factors ◽

Cell Lines ◽

Multilineage Differentiation ◽

Pluripotent Cells ◽

Differentiation Potential ◽

Developmental Potential ◽

Pluripotency Factors ◽

Stem Cell Lines

Pluripotent cells in embryos are situated near the apex of the hierarchy of developmental potential. They are capable of generating all cell types of the mammalian body proper. Therefore, they are the exemplar of stem cells. In vivo, pluripotent cells exist transiently and become expended within a few days of their establishment. Yet, when explanted into artificial culture conditions, they can be indefinitely propagated in vitro as pluripotent stem cell lines. A host of transcription factors and regulatory genes are now known to underpin the pluripotent state. Nonetheless, how pluripotent cells are equipped with their vast multilineage differentiation potential remains elusive. Consensus holds that pluripotency transcription factors prevent differentiation by inhibiting the expression of differentiation genes. However, this does not explain the developmental potential of pluripotent cells. We have presented another emergent perspective, namely, that pluripotency factors function as lineage specifiers that enable pluripotent cells to differentiate into specific lineages, therefore endowing pluripotent cells with their multilineage potential. Here we provide a comprehensive overview of the developmental biology, transcription factors, and extrinsic signaling associated with pluripotent cells, and their accompanying subtypes, in vitro heterogeneity and chromatin states. Although much has been learned since the appreciation of mammalian pluripotency in the 1950s and the derivation of embryonic stem cell lines in 1981, we will specifically emphasize what currently remains unclear. However, the view that pluripotency factors capacitate differentiation, recently corroborated by experimental evidence, might perhaps address the long-standing question of how pluripotent cells are endowed with their multilineage differentiation potential.

Download Full-text

Fetal hemoglobin in paroxysmal nocturnal hemoglobinuria (PNH): evidence for derivation of HbF-containing erythrocytes (F cells) from the PNH clone as well as from normal hemopoietic stem cell lines

Blood ◽

10.1182/blood.v52.4.740.740 ◽

1978 ◽

Vol 52 (4) ◽

pp. 740-749 ◽

Cited By ~ 10

Author(s):

T Papayannopoulou ◽

W Rosse ◽

G Stamatoyannopoulos

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Lines ◽

Whole Blood ◽

Paroxysmal Nocturnal Hemoglobinuria ◽

Red Cells ◽

Hemopoietic Stem Cell ◽

Normal Cells ◽

F Cells ◽

Stem Cell Lines

Abstract The cellular distribution of HbF was studied in nine patients with paroxysmal nocturnal hemoglobinuria (PNH) by measuring the level of HbF and determining the number of HbF-containing red cells (F cells) in whole blood and in the population of normal cells obtained after immune lysis of the abnormal erythrocytes. The amounts of HbF and the F cell frequencies found in the normal red cells were strikingly similar to the values seen in whole blood. The observed frequencies of F cells in normal cells best fitted those expected under the assumption that the F cells arise equally from normal hemopoietic stem cells and from the stem cells with the PNH defect. Since PNH appears to be a clonal hemopoietic stem cell disorder, this evidence argues against a derivation of F cells from distinct pluripotent stem cell lines.

Download Full-text