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Biomedical subjects

W Vainchenker

Publications and source records attributed to W Vainchenker.

251 records · Page 14Linked to original sources
PubMed1980

A gamma and G gamma globin chain synthesis in BFU-E colonies from adult, newborn, and fetal subjects and from thalassemic patients.

The G gamma and A gamma content of Hb F produced in cultures of BFU-Es from the blood of normal fetuses, neonates, and adults was determined. The results show that erythroid progenitors produce A gamma and G gamma chains in a ratio characteristic of their ontogenic stage. The analysis of the G gamma/A gamma ratio in culture of BRU-Es from thalassemic patients showed a marked heterogeneity, resembling that observed in freshly drawn cells. These results afford evidence that the type of gamma chain produced is programmed at the level of early erythroid progenitors.

Adult↗
PubMed1980

Congenital dyserythropoietic anemia type III. studies on erythroid differentiation of blood erythroid progenitor cells (BFUE) in vitro.

In order to investigate whether the morphological abnormalities observed in congenital dyserythropoietic anemia type III (CDA III) have a cellular or an environmental origin; BFUE from the blood of a patient exhibiting a CDA type III were grown in vitro. The progeny derived from these BFUE were subsequently studied at light and electron microscopic level. Giant multinuclear erythroblasts which represent the most prominent finding of CDA III in bone marrow were also found in culture. Nuclear clefts found in vivo were also observed by electron microscopic studies performed on the erythroblasts growing in vitro. In each erythroid colony, morphologically normal and giant multinuclear erythroblasts were intermingled. This finding indicates that the two populations of erythroblasts derive from the same defective stem cell. The studies by indirect immunofluorescence of i antigen was preferentially expressed in the immature erythroblasts as in culture from normal subjects but not in the giant mature erythroblasts. This finding suggests that the excess of i antigen expression of CDA III in vivo is rather the indirect consequence of a stimulation of erythropoiesis than result of the disease.

Adult↗
PubMed1979

Growth of human megakaryocyte colonies in culture from fetal, neonatal, and adult peripheral blood cells: ultrastructural analysis.

Megakaryocyte colonies can be grown in culture from human blood cells and fetal liver cells in plasma clot containing erythropoietin. Megakaryocyte progenitors were found in a fraction of mononuclear cells isolated by Ficoll density gradient centrifugation from adult, neonatal, and fetal blood. Megakaryocytes were identified by their morphology and particularly by their polylobulated nucleus when examined by light microscopy. The megakaryocytic nature of large cells was clearly confirmed by the presence of platelet peroxidase, demarcation membranes, and alpha-granules detected by electron microscopy; in addition mature small megakaryocytes were recognized. Megakaryocyte colonies were seen after 9 days of culture and consisted of 2 to 20 cells. The colonies were pure or mixed with the burst erythroblasts. The mixed colonies were numerous in fetal and neonatal cultures, while pure megakaryocyte colonies were seen three times more frequently in those from adult blood. The total number of colonies was also much lower in adult cultures. In colonies derived from neonatal and fetal cells, megakaryocytes often reached a more complete maturation than in those from the adults, proceeding as far as platelet shedding. This study demonstrates for the first time that a megakaryocyte committed cell present in human blood can develop megakaryocyte colonies in culture.

Blood Cells↗
PubMed1979

Fetal to adult hemoglobin switch in cultures of early erythroid precursors from human fetuses and neonates.

Erythroid burst colonies derived from the cord blood of nine neonates and from the blood and liver of three fetuses aborted after 20 weeks of gestation were grown in plasma clot culture. Their quantitative study revealed a higher proportion of burst-forming units (BFU-Es) in cord blood than in cord blood of normal adults. In addition, colony-forming units (CFU-Es) were present in cord blood but absent from adult blood. Study of haemoglobin synthesis in 14-day cultures of cord blood BFU-Es showed a significantly higher degree of Hb A synthesis than was found in reticulocytes from fresh cord blood; this proportion was, however, similar to that expected in vivo about three weeks after birth. These data suggest that the hemoglobin switch is already programmed in most of the early erythroid precursors present in cord blood or full-term neonates and indicate that the differentiation time is probably of the same order of magnitude in vivo and in vitro. The proportion of Hb A and F synthesis in erythroid bursts was not influenced by the concentration of erythropoietin in the range studied--ie, from 0.5 to 12 international units. Low but identical proportions of Hb A synthesis were found both in erythroid cells from liver after two hours of incubation with [3H]-leucine, and in 14-day liver bursts from fetuses aborted at 20 weeks of gestation.

Adult↗
PubMed1979

Morphological Abnormalities in cultured erythroid colonies (BFU-E) from the blood of two patients with HEMPAS.

The results of cytological and ultrastructural analysis of erythroid burst colonies derived from the peripheral blood of two patients with HEMPAS have been compared to those obtained in normal controls. Using the plasma clot technique, in studies on 10 subjects we confirmed that most of the colonies consisted or erythroblasts with a synchronous and normal maturation involving a wave of nuclear extrusion at day 13. In contrast, the majority of well-haemoglobinized colonies from HEMPAS consisted of numerous bi- or multinucleated erythroblasts displaying the supplementary double membrane beneath their plasma membrane. This excessive membrane may be present as a continuous or fragmented structure in different erythroblasts from the same colony. These findings suggest that the progeny derived from one BFU-E may vary considerably in their morphological defects. Furthermore, one third of the packed colonies appeared to be formed by non-haemoglobinized cells which were clearly identified by electron microscopy as very early erythroblasts. These cells were unable to mature and subsequently lysed. Thus dyserythropoiesis occurred in culture both at early and late stages of maturation. These studies clearly demonstrate that HEMPAS is a disorder resulting from defective erythroid committed cells.

Adult↗
PubMed1979

Megakaryocyte colony formation from human bone marrow precursors.

We report the growth in plasma clot culture of megakaryocyte colonies from adult bone marrow cells with the use of four different sources of erythropoietin (Ep) as the stimulating factor. A major proportion of the megakaryocyte colonies (75%) were pure, while the others were mixed, involving erythroblasts and megakaryocytes. Ultrastructural studies have shown that the maturation of megakaryocytes was essentially normal and that platelet shedding occurred. Megakaryocyte colony formation required a large number of plated cells (greater than 3 X 10(5)/ml). In the absence of erythropoietin, rare spontaneous megakaryocyte colonies could be observed, while no erythroid colonies were present. However, erythropoietin induced a fivefold increase in the total number of colonies. These data suggest that erythropoietin is involved in the differentiation of human megakaryocytes, but that it does not act alone, since another factor related to the number of seeded cells appears essential for the formation of human megakaryocyte colonies.

Animals↗
PubMed1979

Absence of erythroblastic islands in plasma clot culture and their possible reconstitution after clot lysis.

Ultrastructural studies of erythroid colonies derived from human peripheral blood and growing in plasma clot culture have confirmed the absence of a macrophage inside each colony of erythroblasts. However, when macrophages and erythroblasts were liberated from the semisolid media by clot lysis, these two types of cells rapidly acquired intimate contacts, suggesting the reconstitution of any erythroblastic island. The possible significance of this phenomenon is discussed.

Cell Communication↗
PubMed1978

[Differentiation of human megakaryocytes in culture starting from the primordial circulating cells in the newborn].

Human neonatal blood mononuclear cells were seeded in plasma clot containing high dose of a crude erythropietin. Pure megakaryocyte colonies were observed rarely and most of the colonies were mixed, megakaryocytes being located between subcolonies of erythrocytic bursts. The megakaryocytic nature of large cells could be clearly confirmed by the presence of platelet peroxidase, demarcation membranes, and alpha granules detected by electron microscopy; in addition mature micromegakaryocytes were recognized, shedding platelets.

Cell Differentiation↗
PubMedDate not supplied

[Hematopoietic stem cells].

The hematopoietic system is the adult cellular model in which the biology of the stem cells is the best known and may be a model for numerous other tissues. This model is theoretically based on a hierarchy of cells, which begin on a stem cell that differentiates into mature cells through a large number of cellular stages including hematopoietic progenitors. Hematopoietic stem cells have three main properties: (1) Self-renewal capacities. However, in transplantation experiments this property is limited and may be regulated by the stem cell niche. (2) Multipotentiality. Hematopoietic stem cells are capable of differentiation towards all myeloid and lymphoid lineages. However, recent experiments suggest that, like other somatic stem cells, hematopoietic stem cells are capable of differentiating towards non-hematopoietic lineages. The mechanisms of call commitment towards one cell lineage are beginning to be understood and involve competition between transcription factors. (3) Migration. Stem cells are able to travel through the blood. These migration capacities may be an important but underestimated role in the function of hematopoietic stem cells. Mobilization of stem cells by growth factors is now clinically used for hematopoietic transplantation in man. CXCR4 and its ligand, the SDF-1 chemokine, play an important role in stem cell chemotaxis and in their retention in the marrow.

Animals↗
PubMedDate not supplied

Adenoviral supply of active transforming growth factor-beta1 (TGF-beta1) did not prevent lethality in transforming growth factor-beta1-knockout embryos.

In TGF-beta1-knockout mice, TGF-beta1-null conceptuses die during embryonic development with a penetrance of lethality that depends on the mouse genetic background. Studies have suggested that transplacental passage of maternal TGF-beta1 could account for the rescue of some TGF-beta1-null embryos. Herein, we have used an adenovirus-based gene delivery system and a strain of mice where most TGF-beta1-null conceptuses die prior to parturition, to investigate whether an increase in maternal TGF-beta1 during pregnancy would rescue TGF-beta1-null embryos. A single intravenous injection of an adenovirus containing a modified version of TGF-beta1 cDNA (Ad-TGF-beta1S223/S225), coding for a biologically active form of the cytokine, induced a 20-fold increase in plasma TGF-beta1 (active and latent forms) levels for up to 3 months in adult mice. Similar levels of TGF-beta1 were detected in 13-day post coïtum (dpc) embryos from Ad-TGF-beta1-treated mothers, demonstrating an efficient maternal/fetal transfer of the cytokine. However, no increase in the frequencies of TGF-beta1-null neonates nor in day 11.5 dpc TGF-beta1-null conceptuses was observed despite elevated levels of TGF-beta1 delivered throughout gestation. In addition, we show that the high levels of TGF-beta1-titrated in the plasma from Ad-TGF-beta1S223/S225-treated mice were partly the consequence of a stimulation of an autocrine production by exogenous bioactive TGF-beta1. These results indicate that transplacental passage of TGF-beta1 was not effective in rescuing TGF-beta1-null conceptuses from embryonic lethality.

Adenoviridae↗