scholarly journals The Raf‐1 Protein Mediates Insulin‐Like Growth Factor‐Induced Proliferation of Erythroid Progenitor Cells

Stem Cells ◽  
1998 ◽  
Vol 16 (3) ◽  
pp. 200-207 ◽  
Author(s):  
Marilyn R. Sanders ◽  
Hsienwie Lu ◽  
Frederick Walker ◽  
Sandra Sorba ◽  
Nicholas Dainiak
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

scholarly journals Human telomerase is regulated by erythropoietin and transforming growth factor-β in human erythroid progenitor cells

Leukemia ◽  
2007 ◽  
Vol 21 (11) ◽  
pp. 2304-2310 ◽  
Author(s):  
N Prade-Houdellier ◽  
E Frébet ◽  
C Demur ◽  
E-F Gautier ◽  
F Delhommeau ◽  
...  
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells ◽  
Human Telomerase

Insulin-Like Growth Factor II Is an Autocrine Growth Factor To Prevent Apoptosis as Well as To Enhance Proliferation and Maturation of Erythroid Progenitor Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3140-3140
Author(s):  
Taro Nagatomo ◽  
Koichiro Muta ◽  
Shouichi Ohga ◽  
Masayuki Ochiai ◽  
Shunji Hikino ◽  
...  
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Liquid Culture ◽  
Neutralizing Antibody ◽  
Vascular Endothelial ◽  
Insulin Like Growth Factor ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells ◽  
Factor Ii ◽  
Endothelial Growth Factor

Abstract To reveal the novel function of erythroid progenitor cells in fetal erythropoiesis, the gene expression pattern in umbilical cord blood (CB)-derived CD36+ erythroid progenitor cells (EPCs) was analyzed using cDNA microarray containing 240 cytokine and growth factor related genes. Among the genes analyzed, insulin-like growth factor II (IGF-II) gene showed a 124-fold higher level of expression in CB-EPCs, compared with that seen in phytohemagglutinin (PHA)-stimulated adult peripheral blood mononuclear cells (PBMCs) (table1). Real-time PCR revealed that the IGF-II mRNA levels in CB-EPCs were higher than those seen in lymphocytes or monocytes separated from CB or PBMCs. When CB-EPCs were cultured with erythropoietin (EPO) in serum-free medium, the number of erythroid colonies was decreased in the presence of IGF-II-neutralizing antibody. To further assess the role of IGF-II in erythropoiesis, we purified erythroid colony-forming cells (ECFCs) from human umbilical cord blood by magnetic selection and liquid culture with IL-3, stem cell factor and EPO. The expression levels of IGF-II, type 1 or 2 IGF receptor in the mature ECFCs were higher than those in the immature ECFCs. Addition of IGF-II-neutralizing antibody decreased the number of ECFCs in liquid culture with EPO. The anti-proliferative effect of IGF-II-neutralizing antibody was evident in both dimethylthiazole tetrazolium bromide (MTT) and bromodeoxyuridine (BrdU) incorporation assays. When apoptosis of cells was examined using Annexin V, the addition of IGF-II-neutralizing antibody increased apoptosis, thereby indicating the anti-apoptotic effects of IGF-II secreted from erythroid cells. Furthermore, ECFCs failed to undergo normal erythroid maturation in the presence of IGF-II-neutralizing antibody, as assessed by flow cytometric and morphologic analyses. These findings indicate that IGF-II, which is produced by erythroid progenitor cells themselves, has crucial roles in controlling erythropoiesis by modulating apoptosis, proliferation and maturation via an autocrine mechanism. Cytokine and growth factor genes highly expressed in CB-EPCs selected by cDNA microarray analyses ratio gene 124.0 insulin-like growth factor II 7.9 vascular endothelial growth factor 3.9 interleukin 8 3.4 GRO2 oncogene 3.0 GRO1 oncogene 1.6 transforming growth factor, beta 1 1.4 vascular endothelial growth factor B

scholarly journals Insulin-Like Growth Factor Binding Protein-1 Is Elevated in Patients With Polycythemia Vera and Stimulates Erythroid Burst Formation In Vitro

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 1862-1869 ◽  
Author(s):  
Amer M. Mirza ◽  
Shereen Ezzat ◽  
Arthur A. Axelrad
Keyword(s):  
Growth Factor ◽  
Polycythemia Vera ◽  
Progenitor Cells ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells ◽  
Igf I ◽  
Increased Sensitivity ◽  
Igfbp 3

Abstract Previously, we found that, in the myeloproliferative disorder polycythemia vera (PV), circulating erythroid progenitor cells were hypersensitive to insulin-like growth factor I (IGF-I), an effect shown to occur through the IGF-I receptor. Also, in cells of PV patients, the IGF-I receptor was hyperphosphorylated on tyrosine residues under basal conditions, and its tyrosine phosphorylation in response to exogenous IGF-I was strongly augmented. Thus, because IGF-I appeared to play a role in the pathogenesis of PV, we wished to assess its level in the circulation of these patients. Normally, most of the circulating IGF-I is bound to specific high-affinity IGF binding proteins that can regulate its activity. We determined the circulating levels of IGF-I and two of its key binding proteins, IGFBP-1 and IGFBP-3. In two separate experiments, plasma samples from a total of 23 PV patients age- and sex-matched with 41 normal individuals were compared by radioimmunoassay. The levels of IGFBP-1 in patients with PV (37.80 ± 4.33 μg/L) were more than fourfold higher than in normals (9.34 ± 1.34 μg/L) or patients with secondary erythrocytosis (9.47 ± 1.96 μg/L), whereas the plasma concentrations of IGFBP-3 and IGF-I in these patients were similar to those of normal subjects. Because circulating IGFBP-1 levels may be influenced by insulin, we measured the concentrations of insulin in the same samples. Our data showed that the elevation of circulating IGFBP-1 in PV could not be attributed to low levels of insulin in these patients. The substantial increase in concentration of IGFBP-1 was confirmed on ligand blots performed with 125I–IGF-I. IGFBP-1 can be either inhibitory or stimulatory to the action of IGF-I under different conditions. We reasoned that if IGFBP-1 were stimulatory for erythropoiesis, an elevated IGFBP-1 level could help to explain the increased sensitivity to IGF-I observed in PV. If IGFBP-1 were inhibitory, it might suggest a compensatory mechanism in which a hyperphosphorylated IGF-I receptor in PV might induce a negative modulator of IGF-I action, in this case IGFBP-1. To distinguish between these two hypotheses, we titrated the effect of IGFBP-1 in the presence of IGF-I with respect to erythroid burst formation and found that IGFBP-1 was strikingly stimulatory. The elevated level of IGFBP-1 coupled with its ability to stimulate erythroid burst formation provide an attractive mechanism to account for the increased sensitivity of erythroid progenitor cells to IGF-I and the consequent overproduction of red blood cells characteristic of PV.

Ex Vivo Expanded Erythroid Progenitor Cells Augment Therapeutic Angiogenesis by Extensive Cytokine Production.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3966-3966
Author(s):  
Koichiro Muta ◽  
Shuzi Sasaki ◽  
Min Zhang ◽  
Toyoshi Inoguchi ◽  
Yasunobu Abe
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Blood Perfusion ◽  
Therapeutic Angiogenesis ◽  
Vascular Endothelial ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells ◽  
Endothelial Growth Factor ◽  
Salvage Rate

Abstract Alternative therapies for clinical limb ischemia have become very important for patients with peripheral ischemic disease (PAD), who cannot undergo surgical or percutaneous revascularization. Delivery of angiogenic growth factors, such as vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), hepatocyte growth factor (HGF), stromal cell-derived factor-1α (SDF-1α), and placental growth factor (PlGF), using recombinant proteins or gene transfer have been considered for alternative treatment of PAD and their efficacies have been demonstrated. Recent reports have demonstrated that erythroid progenitor cells contain and secrete various angiogenic cytokines. Although this suggest an important role for erythroid progenitor cells in angiogenesis, no studies have reported in vivo evidence of angiogenesis induction by erythroid progenitor cells. Here, the impact of purified human erythroid colony-forming cell (ECFC) implantation on therapeutic angiogenesis was investigated in murine models of hindlimb ischemia. ECFCs were purified from human peripheral blood and expanded ex vivo. ECFCs from day 5 to 7, those are considered as erythroid progenitors of colony-forming unit erythroid(CFU-E) level of maturation, showed the highest vascular endothelial growth factor (VEGF) productivity. THerefore, day-6 ECFCs were used for the following experiments. Day-6 ECFCs contained larger amounts of VEGF and fibroblast growth factor-2 (FGF-2) than peripheral blood mononuclear cells (PBMNCs). In tubule formation assays with human umbilical vein endothelial cells, ECFCs stimulated 1.5-fold more capillary growth than PBMNCs, and this effect was suppressed by antibodies against VEGF and FGF-2. Using an immunodeficient hindlimb ischemia model and laser Doppler imaging, we evaluated the limb salvage rate and blood perfusion after intramuscular implantation of ECFCs. ECFC implantation increased both the salvage rate (38% vs. 0%, P<0.05) and the blood perfusion (82.8% vs. 65.6%, P<0.01). The capillary density was 1.6-fold higher in the ECFC group than in the control group. Implantation of ECFCs promoted angiogenesis in ischemic limbs by supplying angiogenic cytokines (VEGF and FGF-2), suggesting a possible novel strategy for therapeutic angiogenesis for the patients with PDA.

Therapeutic angiogenesis by ex vivo expanded erythroid progenitor cells

2007 ◽  
Vol 292 (1) ◽  
pp. H657-H665 ◽  
Author(s):  
Shuji Sasaki ◽  
Toyoshi Inoguchi ◽  
Koichiro Muta ◽  
Yasunobu Abe ◽  
Min Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Blood Perfusion ◽  
Therapeutic Angiogenesis ◽  
Erythroid Cells ◽  
Hindlimb Ischemia ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells ◽  
Salvage Rate ◽  
Angiogenic Cytokines

Recent reports have demonstrated that erythroid progenitor cells contain and secrete various angiogenic cytokines. Here, the impact of erythroid colony-forming cell (ECFC) implantation on therapeutic angiogenesis was investigated in murine models of hindlimb ischemia. During the in vitro differentiation, vascular endothelial growth factor (VEGF) secretion by ECFCs was observed from day 3 (burst-forming unit erythroid cells) to day 10 (erythroblasts). ECFCs from day 5 to day 7 (colony-forming unit erythroid cells) showed the highest VEGF productivity, and day 6 ECFCs were used for the experiments. ECFCs contained larger amounts of VEGF and fibroblast growth factor-2 (FGF-2) than peripheral blood mononuclear cells (PBMNCs). In tubule formation assays with human umbilical vein endothelial cells, ECFCs stimulated 1.5-fold more capillary growth than PBMNCs, and this effect was suppressed by antibodies against VEGF and FGF-2. Using an immunodeficient hindlimb ischemia model and laser-Doppler imaging, we evaluated the limb salvage rate and blood perfusion after intramuscular implantation of ECFCs. ECFC implantation increased both the salvage rate (38% vs. 0%, P < 0.05) and the blood perfusion (82.8% vs. 65.6%, P < 0.01). In addition, ECFCs implantation also significantly increased capillaries with recruitment of vascular smooth muscle cells and the capillary density was 1.6-fold higher than in the control group. Continuous production of human VEGF from ECFCs in the skeletal muscle was confirmed at least 7 days after the implantation. Implantation of ECFCs promoted angiogenesis in ischemic limbs by supplying angiogenic cytokines (VEGF and FGF-2), suggesting a possible novel strategy for therapeutic angiogenesis.

Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitro

2000 ◽  
Vol 111 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Katsuto Takenaka ◽  
Mine Harada ◽  
Tomoaki Fujisaki ◽  
Koji Nagafuji ◽  
Shinichi Mizuno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Progenitor Cells ◽  
Thymic Epithelial Cells ◽  
Erythroid Progenitor ◽  
Term Survival ◽  
Long Term Survival ◽  
Erythroid Progenitor Cells

scholarly journals Fetal erythropoiesis in steel mutant mice. III. Defect in differentiation from BFU-E to CFU-E during early development

Blood ◽  
1978 ◽  
Vol 51 (3) ◽  
pp. 539-547 ◽  
Author(s):  
DH Chui ◽  
SK Liao ◽  
K Walker
Keyword(s):  
Progenitor Cells ◽  
Early Development ◽  
The Other ◽  
Mutant Mice ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells ◽  
Other Hand ◽  
Colony Forming Units ◽  
Fetal Erythropoiesis

Abstract Erythroid progenitor cells in +/+ and Sl/Sld fetal livers manifested as burst-forming units-erythroid (BFU-E) and colony-forming units- erythroid (CFU-E) were assayed in vitro during early development. The proportion of BFU-E was higher as mutant than in normal fetal livers. On the other hand, the proportion of CFU-E was less in the mutant than in the normal. These results suggest that the defect in Sl/Sld fetal hepatic erythropoiesis is expressed at the steps of differentiation that effect the transition from BFU-E to CFU-E.

scholarly journals Tumor Immune Evasion Induced by Dysregulation of Erythroid Progenitor Cells Development

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 870
Author(s):  
Tomasz M. Grzywa ◽  
Magdalena Justyniarska ◽  
Dominika Nowis ◽  
Jakub Golab
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Progenitor Cells ◽  
Cancer Progression ◽  
Immune Evasion ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Interleukin 10 ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

Cancer cells harness normal cells to facilitate tumor growth and metastasis. Within this complex network of interactions, the establishment and maintenance of immune evasion mechanisms are crucial for cancer progression. The escape from the immune surveillance results from multiple independent mechanisms. Recent studies revealed that besides well-described myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) or regulatory T-cells (Tregs), erythroid progenitor cells (EPCs) play an important role in the regulation of immune response and tumor progression. EPCs are immature erythroid cells that differentiate into oxygen-transporting red blood cells. They expand in the extramedullary sites, including the spleen, as well as infiltrate tumors. EPCs in cancer produce reactive oxygen species (ROS), transforming growth factor β (TGF-β), interleukin-10 (IL-10) and express programmed death-ligand 1 (PD-L1) and potently suppress T-cells. Thus, EPCs regulate antitumor, antiviral, and antimicrobial immunity, leading to immune suppression. Moreover, EPCs promote tumor growth by the secretion of growth factors, including artemin. The expansion of EPCs in cancer is an effect of the dysregulation of erythropoiesis, leading to the differentiation arrest and enrichment of early-stage EPCs. Therefore, anemia treatment, targeting ineffective erythropoiesis, and the promotion of EPC differentiation are promising strategies to reduce cancer-induced immunosuppression and the tumor-promoting effects of EPCs.

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