Search results for "Haematopoiesi"
showing 10 items of 183 documents
EPCR Guides Hematopoietic Stem Cells Homing to the Bone Marrow Independently of Niche Clearance
2016
Abstract Bone marrow (BM) homing and lodgment of long-term repopulating hematopoietic stem cells (LT-HSCs) are active and essential first steps during embryonic development and in clinical stem cell transplantation. Rare, BM LT-HSCs endowed with the highest self-renewal and durable repopulation potential, functionally express the anticoagulant endothelial protein C receptor (EPCR) and PAR1. In addition to coagulation and inflammation, EPCR-PAR1 signaling independently controls a BM LT-HSC retention-release switch via regulation of nitric oxide (NO) production within LT-HSCs. EPCR+ LT-HSCs are maintained in thrombomodulin+ (TM) periarterial BM microenvironments via production of activated pr…
Developmental programming of adult haematopoiesis system
2019
The Barker hypothesis of ‘foetal origin of adult diseases’ has led to emphasize the concept of ‘developmental programming’, based on the crucial role of epigenetic factors. Accordingly, it has been demonstrated that parental adversity (before conception and during pregnancy) and foetal factors (i.e., hypoxia, malnutrition and placental insufficiency) permanently modify the physiological systems of the progeny, predisposing them to premature ageing and chronic disease during adulthood. Thus, an altered functionality of the endocrine, immune, nervous and cardiovascular systems is observed in the progeny. However, it remains to be understood whether the haematopoietic system itself also repres…
AN IL-6/IL-6 SOLUBLE RECEPTOR (IL-6R) HYBRID PROTEIN (H-IL-6) INDUCES EPO-INDEPENDENT ERYTHROID DIFFERENTIATION IN HUMAN CD34+CELLS
2000
H-IL-6 is a hybrid protein constructed to contain IL-6 and its soluble receptor linked by a flexible peptide chain. Here we show that H-IL-6 strongly enhances proliferation of human CD34(+)cells in serum-free liquid culture, and that the majority of the cells generated belong to the erythroid lineage, being positive for the marker Glycophorin A. Conversely, H-IL-6 does not increase the number of myeloid, CD13-positive cells. Comparable effects are observed on progenitors from cord blood and adult peripheral blood. Therefore, H-IL-6 triggers an erythroid-inducing signal in haematopoietic progenitor cells, independently from erythropoietin (EPO).
In utero fetal liver hematopoietic stem cell transplantation: is there a role for alloreactive T lymphocytes?
2000
The use of hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy, although this approach has provided quite heterogeneous results. Flake and Zanjani have provided an excellent updated review of the current knowledge of in
Inhibition of Fibroblast Growth Factor-23 (FGF-23) Rescues Bone and Hematopoietic Stem Cell Niche Defects in Beta-Thalassemia, Uncovering the Missing…
2021
Abstract The bone marrow (BM) niche regulation and interactions with hematopoietic stem cells (HSC) have been extensively studied in steady state conditions and malignancies, but are still underexplored in hematological inherited disorders. We provided the first demonstration of impaired HSC function caused by an altered BM niche in a non-malignant disease, beta-thalassemia (BT) (Aprile et al., Blood 2020). BT is a globally widespread congenital hemoglobin disorder, resulting in severe anemia, ineffective erythropoiesis and multi-organ secondary complications, including bone alterations. Correction of the genetic defect is achieved by transplantation of HSC from healthy donors or autologous…
Proliferation of gastrointestinal carcinoma cells by T lymphocyte factors interleukin-3 and granulocyte-macrophage colony-stimulating factor
1991
Hematopoietic growth factors have been well characterized by cDNA cloning in recent years. In order to determine the influence of rhGM-CSF and rhIL-3 on epithelial cells of the gastrointestinal tract, their influence on in vitro cultured gastric and pancreas cancer cells was determined. A more than two-fold enhancement of proliferation was observed by IL-3 and GM-CSF in Mz-Sto-1 gastric and 818-4 pancreas carcinoma cells, applying a sensitive microculture system which allows precise quantification. The highest growth rates were obtained adding 1-10 ng/ml of the growth factors, but even picogram amounts were effective. Expression of mRNA for GM-CSF and IL-3 remained undetectable in the cell …
Introduction to stem cell biology in vitro. Threshold to the future.
1999
Abstract: Transplantable hematopoietic cells with multilineage reconstituting ability can be quantitated in suspensions of human or murine cells using similar assay procedures. The incorporation into these assays of stringently defined functional endpoints ensures a high degree of specificity for the cells detected. Application of these assays to stem cell-containing suspensions after they have been stimulated for several days with defined cytokines in vitro, or by a mixture of defined and/or undefined factors in vivo, has shown that net amplifications in these populations can be obtained under both circumstances. Such studies have allowed cytokine conditions that support stem cell self-ren…
The function of the soluble IL-6 receptor in vivo.
1996
Interleukin-6 (IL-6) is considered an important mediator of acute inflammatory responses. Moreover, IL-6 functions as a differentiation and growth factor of hematopoietic precursor cells, B-cells, T-cells, keratinocytes, neuronal cells, osteoclasts and endothelial cells. IL-6 exhibits its action via a receptor complex consisting of a specific IL-6 receptor (IL-6R) and a signal-transducing subunit (gp130). Soluble forms of both receptor components are generated by shedding and are found in patients with various diseases such as AIDS, rheumatoid arthritis and others. The function of the soluble IL-6R in vivo is unknown. To discriminate between the biologic function of hIL-6 alone and that of …
Cdc42 in osterix-expressing cells alters osteoblast behavior and myeloid lineage commitment
2021
Osteoblasts are not only responsible for bone formation. They also support hematopoiesis. This requires responding to cues originating from several signaling pathways, a task performed by Rho GTPases. We therefore examined several transgenic mouse models and used inhibitors of Cdc42 in vitro. Deletion of Cdc42 in vivo using the Osterix promoter suppressed osteoblast function, while its deletion in differentiating osteoblasts using the Collagen-a1(I) promoter decreased osteoblast numbers. In both cases, bone mineral density diminished confirming the importance of Cdc42. Evaluation of hematopoiesis revealed that deletion of Cdc42 using the Osterix, but not the Collagen-a1(I) promoter increase…
Cytomegalovirus inhibits the engraftment of donor bone marrow cells by downregulation of hemopoietin gene expression in recipient stroma
1998
ABSTRACT Cytomegalovirus (CMV) disease after bone marrow (BM) transplantation is often associated with BM graft failure. There are two possible reasons for such a correlation. First, a poor hematopoietic reconstitution of unrelated etiology could promote the progression of CMV infection by the lack of immune control. Alternatively, CMV infection could interfere with the engraftment of donor BM cells in recipient BM stroma. Evidence for a causative role of CMV in BM aplasia came from studies in long-term BM cultures and from the murine in vivo model of CMV-induced aplastic anemia. A deficiency in the expression of essential stromal hemopoietins, such as stem cell factor (SCF), has indicated …