Effects of Glucan Supplementation on Aged Hematopoietic Progenitor Cells

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Vetvicka V ◽  
◽  
Vetvickova J ◽  

Age related changes in activity of hematopoietic progenitor cells led us to investigate the possibility that glucan supplementation might overcome this suppression. In our study, we focused on differences of these cells in young (8 weeks old) and old (18 months old) mice after supplementation of yeast-derived insoluble glucan. Our results showed significant differences in reconstitution ability of progenitor cells as well as changes in level of stromal cell-derived factor 1α between young and old mice exist and can be partly restored by glucan supplementation.

2001 ◽  
Vol 29 (3) ◽  
pp. 345-355 ◽  
Author(s):  
Andrés Hidalgo ◽  
Francisco Sanz-Rodrı́guez ◽  
José Luis Rodrı́guez-Fernández ◽  
Beatriz Albella ◽  
Carolina Blaya ◽  
...  

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2587-2595 ◽  
Author(s):  
Raffaella Guerriero ◽  
Gianfranco Mattia ◽  
Ugo Testa ◽  
Cristiana Chelucci ◽  
Giampiero Macioce ◽  
...  

Abstract The alpha chemokine receptor CXCR4 has been shown to be expressed on human hematopoietic progenitor cells and during the megakaryocytic differentiation pathway. Stromal cell–derived factor 1 (SDF-1) is the ligand for CXCR4. In this study, the role of SDF-1α in megakaryocytopoiesis was investigated. CD34+ progenitors purified from peripheral blood were grown in serum-free liquid suspension culture supplemented with thrombopoietin to obtain a virtually pure megakaryocytic progeny. In this condition, the addition of SDF-1α gives rise to megakaryocytes (MKs) showing an increased DNA content and a rise of lobated nuclei, as compared with untreated cells: at day 5, approximately 20% of the cells already showed the presence of more than one nuclear lobe versus fewer than 5% in the control cells; at day 12, approximately 85% of the cells were of large size and markedly polyploid, whereas approximately 60% of the control cells were polyploid, showed fewer lobes, and were a smaller size. This effect was dose-dependent and did not affect the megakaryocytic proliferation. Experiments with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 suggested a role for MAPK pathway on SDF-1α–induced endomitosis. Furthermore, SDF-1α induced a significant increase in the number of proplatelet-bearing MKs and promoted the migration of megakaryocytic cells. Treatment with SDF-1α caused reduction in CXCR4 abundance on the plasma membrane, seemingly owing to receptor internalization. Furthermore, the presence of SDF-1α did not affect the expression of megakaryocytic markers, indicating that differentiation and polyploidization are independently regulated events.


Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1363-1372 ◽  
Author(s):  
Takayuki Nakayama ◽  
Noriko Mutsuga ◽  
Giovanna Tosato

AbstractThe chemokine stromal cell–derived factor-1 (SDF-1) is constitutively expressed by bone marrow stromal cells and plays key roles in hematopoiesis. Fibroblast growth factor 2 (FGF2), a member of the FGF family that plays important roles in developmental morphogenic processes, is abnormally elevated in the bone marrow from patients with clonal myeloid disorders and other disorders where normal hematopoiesis is impaired. Here, we report that FGF2 reduces SDF-1 secretion and protein content in bone marrow stromal cells. By inhibiting SDF-1 production, FGF2 compromises stromal cell support of hematopoietic progenitor cells. Reverse-transcriptase–polymerase chain reaction (RT-PCR) analysis revealed that bone marrow stromal cells express 5 FGF receptors (FGFRs) among the 7 known FGFR subtypes. Blocking experiments identified FGFR1 IIIc as the receptor mediating FGF2 inhibition of SDF-1 expression in bone marrow stromal cells. Analysis of the mechanisms underlying FGF2 inhibition of SDF-1 production in bone marrow stromal cells revealed that FGF2 reduces the SDF-1 mRNA content by posttranscriptionally accelerating SDF-1 mRNA decay. Thus, we identify FGF2 as an inhibitor of SDF-1 production in bone marrow stromal cells and a regulator of stromal cell supportive functions for hematopoietic progenitor cells.


Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1436-1444 ◽  
Author(s):  
Y Shiota ◽  
JG Wilson ◽  
K Harjes ◽  
ED Zanjani ◽  
M Tavassoli

Abstract The adhesion of hematopoietic progenitor cells to bone marrow stromal cells is critical to hematopoiesis and involves multiple effector molecules. Stromal cell molecules that participate in this interaction were sought by analyzing the detergent-soluble membrane proteins of GBI/6 stromal cells that could be adsorbed by intact FDCP-1 progenitor cells. A single-chain protein from GBI/6 cells having an apparent molecular weight of 37 Kd was selectively adsorbed by FDCP-1 cells. This protein, designated p37, could be surface-radiolabeled and thus appeared to be exposed on the cell membrane. An apparently identical 37- Kd protein was expressed by three stromal cell lines, by Swiss 3T3 fibroblastic cells, and by FDCP-1 and FDCP-2 progenitor cells. p37 was selectively adsorbed from membrane lysates by a variety of murine hematopoietic cells, including erythrocytes, but not by human erythrocytes. Binding of p37 to cells was calcium-dependent, and was not affected by inhibitors of the hematopoietic homing receptor or the cell-binding or heparin-binding functions of fibronectin. It is proposed that p37 may be a novel adhesive molecule expressed on the surface of a variety of hematopoietic cells that could participate in both homotypic and heterotypic interactions of stromal and progenitor cells.


Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2436-2443 ◽  
Author(s):  
MC Yoder ◽  
VE Papaioannou ◽  
PP Breitfeld ◽  
DA Williams

Abstract The mechanisms involved in the induction of yolk sac mesoderm into blood islands and the role of visceral endoderm and mesoderm cells in regulating the restricted differentiation and proliferation of hematopoietic cells in the yolk sac remain largely unexplored. To better define the role of murine yolk sac microenvironment cells in supporting hematopoiesis, we established cell lines from day-9.5 gestation murine yolk sac visceral endoderm and mesoderm layers using a recombinant retrovirus vector containing Simian virus 40 large T- antigen cDNA. Obtained immortalized cell lines expressed morphologic and biosynthetic features characteristic of endoderm and mesoderm cells from freshly isolated yolk sacs. Similar to the differentiation of blood island hematopoietic cells in situ, differentiation of hematopoietic progenitor cells in vitro into neutrophils was restricted and macrophage production increased when bone marrow (BM) progenitor cells were cultured in direct contact with immortalized yolk sac cell lines as compared with culture on adult BM stromal cell lines. Yolk sac- derived cell lines also significantly stimulated the proliferation of hematopoietic progenitor cells compared with the adult BM stromal cell lines. Thus, yolk sac endoderm- and mesoderm-derived cells, expressing many features of normal yolk sac cells, alter the growth and differentiation of hematopoietic progenitor cells. These cells will prove useful in examining the cellular interactions between yolk sac endoderm and mesoderm involved in early hematopoietic stem cell proliferation and differentiation.


Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4523-4530 ◽  
Author(s):  
Robert Möhle ◽  
Frank Bautz ◽  
Shahin Rafii ◽  
Malcolm A.S. Moore ◽  
Wolfram Brugger ◽  
...  

Abstract The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4 (fusin, LESTR) are likely to be involved in the trafficking of hematopoietic progenitor and stem cells, as suggested by the reduced bone marrow hematopoiesis in SDF-1–deficient mice and the chemotactic effect of SDF-1 on CD34+ progenitor cells. Migration of leukemic cells might also depend on the expression of chemokine receptors. Therefore, we analyzed expression of CXCR-4 on mobilized normal CD34+ progenitors and leukemic cells. In addition, SDF-1–induced transendothelial migration across a bone marrow endothelial cell layer was assessed in vitro. By flow cytometry, CXCR-4 was found to be expressed in significant amounts on circulating CD34+ hematopoietic progenitor cells, including more primitive subsets (CD34+/CD38− and CD34+/Thy-1+ cells). In accordance with the immunofluorescence data, CD34+ progenitors efficiently migrated across endothelium in response to SDF-1 containing conditioned medium from the stromal cell line MS-5. Leukemic blasts (mostly CD34+) from patients with acute myeloblastic leukemia (AML) expressed variable amounts of CXCR-4, which was functionally active, as demonstrated by a positive correlation between the SDF-1–induced transendothelial migration and the cell surface density of CXCR-4 (r = 0.97). Also recombinant SDF-1β induced migration of CXCR-4–positive leukemic blasts. The effect of both conditioned medium and recombinant SDF-1 was inhibited by a CXCR-4 blocking antibody. In contrast, CD34+ leukemic cell lines (KG1, KG1a, Kasumi-1, MOLM-1) expressed low levels or were negative for CXCR-4, and did not migrate. By reverse transcriptase-polymerase chain reaction (RT-PCR), however, basal levels of CXCR-4 mRNA were also detected in all leukemic cell lines. We conclude that CXCR-4 is expressed on CD34+cells including more primitive, pluripotent progenitors, and may therefore play a role in the homing of hematopoietic stem cells. CXCR-4 expressed in variable amounts on primary AML leukemic cells is functionally active and may be involved in the trafficking of malignant hematopoietic cells.


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