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

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.

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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.bloodjournal524740 ◽

1978 ◽

Vol 52 (4) ◽

pp. 740-749

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

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.

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Circulating Primitive Stem Cells in Paroxysmal Nocturnal Hemoglobinuria (PNH) Are Predominantly Normal in Phenotype But Granulocyte Colony-Stimulating Factor Treatment Mobilizes Mainly PNH Stem Cells

Blood ◽

10.1182/blood.v91.12.4504 ◽

1998 ◽

Vol 91 (12) ◽

pp. 4504-4508 ◽

Cited By ~ 15

Author(s):

Roderick J. Johnson ◽

Andy C. Rawstron ◽

Steve Richards ◽

Gareth J. Morgan ◽

Derek R. Norfolk ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Peripheral Blood ◽

Paroxysmal Nocturnal Hemoglobinuria ◽

Autologous Transplantation ◽

Hemopoietic Stem Cell ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Peripheral Blood Stem Cells ◽

Stimulating Factor

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia resulting from a somatic mutation in a hemopoietic stem cell. In most cases of hemolytic PNH, the majority of the marrow cells are derived from the PNH clone. Recent evidence has indicated, however, that the majority of the most primitive peripheral blood stem cells (PBSCs) in PNH appear to be of normal phenotype. This has led to tentative suggestions that normal PBSCs could be collected and used for autologous transplantation. We have investigated this possibility in four PNH patients by treating them with granulocyte colony-stimulating factor (G-CSF) in an attempt to mobilize normal progenitors. The expression of glycosylphosphatidylinositol (GPI)-linked proteins was analyzed by flow cytometry on mature neutrophils, late stem cells (CD34+/CD38+), and primitive stem cells (CD34+/CD38−). The phenotyping and stem cell quantitation was performed in steady-state blood and post–G-CSF administration. The most primitive PBSCs (CD34+/CD38−) were almost all normal before G-CSF treatment, even when the patients' neutrophils were mainly PNH. However, after G-CSF, the cells that were mobilized into the peripheral blood were of a similar phenotype to the mature neutrophils, ie, mainly PNH. It is possible that PNH-stem cells are preferentially destroyed by complement in the peripheral blood leaving only normal cells in the circulation. After G-CSF, the PNH cells in the marrow are released into the blood. Our findings suggest that it would be difficult to collect sufficient numbers of normal stem cells for autologous transplantation.

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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.

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Derivation of Human Embryonic Stem Cell Lines From Biopsied Blastomeres Without Destruction of the Embryo—a Critical Step Towards Creating Personalized Stem Cells for IVF Babies

Fertility and Sterility ◽

10.1016/j.fertnstert.2008.02.022 ◽

2008 ◽

Vol 89 (4) ◽

pp. S7

Author(s):

A. Krtolica ◽

E. Caceres ◽

R. Foulk ◽

C. Simon ◽

D. Ilic

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Embryonic Stem Cell ◽

Cell Lines ◽

Human Embryonic Stem Cell ◽

Embryonic Stem ◽

Critical Step ◽

Stem Cell Lines

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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.

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Male germ line stem cells: from cell biology to cell therapy

Reproduction Fertility and Development ◽

10.1071/rd03046 ◽

2003 ◽

Vol 15 (6) ◽

pp. 323 ◽

Cited By ~ 2

Author(s):

David Pei-Cheng Lin ◽

Ming-Yu Chang ◽

Bo-Yie Chen ◽

Han-Hsin Chang

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Lines ◽

Germ Cells ◽

Germ Line ◽

Current Status ◽

Seminiferous Tubules ◽

Male Germ Line ◽

Male Germ Cells ◽

Stem Cell Lines

Research using stem cells has several applications in basic biology and clinical medicine. Recent advances in the establishment of male germ line stem cells provided researchers with the ability to identify, isolate, maintain, expand and differentiate the spermatogonia, the primitive male germ cells, as cell lines under in vitro conditions. The ability to culture and manipulate stem cell lines from male germ cells has gradually facilitated research into spermatogenesis and male infertility, to an extent beyond that facilitated by the use of somatic stem cells. After the introduction of exogenous genes, the spermatogonial cells can be transplanted into the seminiferous tubules of recipients, where the transplanted cells can contribute to the offspring. The present review concentrates on the origin, life cycle and establishment of stem cell lines from male germ cells, as well as the current status of transplantation techniques and the application of spermatogonial stem cell lines.

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Generation of human pluripotent stem cell lines (iPSCs) from mesenchymal stem cells (MSCs) from three elderly patients with osteoarthritis

Stem Cell Research ◽

10.1016/j.scr.2020.101721 ◽

2020 ◽

Vol 44 ◽

pp. 101721 ◽

Cited By ~ 2

Author(s):

Lydiane Pichard ◽

Jean-Marc Brondelo ◽

Fabienne Becker ◽

Romain Desprat ◽

Frédéric De Ceuninck ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Elderly Patients ◽

Cell Lines ◽

Pluripotent Stem Cell ◽

Human Pluripotent Stem Cell ◽

Stem Cell Lines

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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.

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Expression of miRNAs from the Imprinted DLK1/DIO3 Locus Signals the Osteogenic Potential of Human Pluripotent Stem Cells

Cells ◽

10.3390/cells8121523 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1523 ◽

Cited By ~ 1

Author(s):

Laetitia Barrault ◽

Jacqueline Gide ◽

Tingting Qing ◽

Lea Lesueur ◽

Jorg Tost ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Osteogenic Differentiation ◽

Cell Lines ◽

Pluripotent Stem Cells ◽

Pluripotent Stem Cell ◽

Human Pluripotent Stem Cells ◽

Osteogenic Potential ◽

Human Pluripotent Stem Cell ◽

Stem Cell Lines

Substantial variations in differentiation properties have been reported among human pluripotent cell lines (hPSC), which could affect their utility and clinical safety. We characterized the variable osteogenic capacity observed between different human pluripotent stem cell lines. By focusing on the miRNA expression profile, we demonstrated that the osteogenic differentiation propensity of human pluripotent stem cell lines could be associated with the methylation status and the expression of miRNAs from the imprinted DLK1/DIO3 locus. More specifically, quantitative analysis of the expression of six different miRNAs of that locus prospectively identified human embryonic stem cells and human-induced pluripotent stem cells with differential osteogenic differentiation capacities. At the molecular and functional levels, we showed that these miRNAs modulated the expression of the activin receptor type 2B and the downstream signal transduction, which impacted osteogenesis. In conclusion, miRNAs of the imprinted DLK1/DIO3 locus appear to have both a predictive value and a functional impact in determining the osteogenic fate of human pluripotent stem cells.

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