scholarly journals Binding of primitive hematopoietic progenitor cells to marrow stromal cells involves heparan sulfate

Blood ◽  
1992 ◽  
Vol 80 (4) ◽  
pp. 912-919 ◽  
Author(s):  
M Siczkowski ◽  
D Clarke ◽  
MY Gordon
Keyword(s):  
Heparan Sulfate ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Progenitor Cell ◽  
Time Course ◽  
Biochemical Properties ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Binding Interaction ◽  
Binding Phase

Blast colony-forming cells (BI-CFC) and pre-colony-forming unit- granulocyte, monocyte (CFU-GM) in human bone marrow bind to marrow- derived stromal layers grown in the presence of methylprednisolone (MP+), but do not bind to stroma grown without MP (MP-). The BI-CFC bind to stroma and form colonies when overlaid with agar; the pre-CFU- GM bind to stroma and release CFU-GM into the supernatant culture medium (delta assay). These two classes of progenitor may represent similar stages of hematopoietic cell development. Their binding to stroma depends on the presence of heparan sulfate proteoglycan (HS-PG) in the extracellular matrix secreted by the stromal cells. Here, we have analyzed the functional and biochemical properties of HS-PG isolated from MP+ and MP- stromal cultures. HS-PG or isolated HS glycosaminoglycan (GAG) side chains partially blocked progenitor cell binding when they were added to the 2-hour binding phase of the BI-CFC or delta assays. Gel electrophoresis of HS-PG resolved more bands in matrix preparations from MP+ cultures than in preparations from MP- cultures. The blocking activity of the eluted MP+ HS-PG bands depended partly on the amount of GAG attached to the protein core and presumably partly on the structure of the core itself. Time course studies demonstrated that the HS-dependent phase of the binding interaction was limited to the first 30 to 60 minutes of the 2-hour binding phase. The different blocking effects of MP+ and MP- HS indicate that they have different biochemical properties. The HS-GAG in MP+ stroma has a higher degree of sulfation and a greater negative charge to mass ratio compared with MP- HS-GAG. Variations in HS may determine specific binding by hematopoietic progenitor cells and a heparan sulfate receptor is envisaged as acting in concert with further cell adhesion molecules (CAMs) on the progenitor cell surface.

scholarly journals Binding of primitive hematopoietic progenitor cells to marrow stromal cells involves heparan sulfate

Blood ◽  
1992 ◽  
Vol 80 (4) ◽  
pp. 912-919 ◽  
Author(s):  
M Siczkowski ◽  
D Clarke ◽  
MY Gordon
Keyword(s):  
Heparan Sulfate ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Progenitor Cell ◽  
Time Course ◽  
Biochemical Properties ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Binding Interaction ◽  
Binding Phase

Abstract Blast colony-forming cells (BI-CFC) and pre-colony-forming unit- granulocyte, monocyte (CFU-GM) in human bone marrow bind to marrow- derived stromal layers grown in the presence of methylprednisolone (MP+), but do not bind to stroma grown without MP (MP-). The BI-CFC bind to stroma and form colonies when overlaid with agar; the pre-CFU- GM bind to stroma and release CFU-GM into the supernatant culture medium (delta assay). These two classes of progenitor may represent similar stages of hematopoietic cell development. Their binding to stroma depends on the presence of heparan sulfate proteoglycan (HS-PG) in the extracellular matrix secreted by the stromal cells. Here, we have analyzed the functional and biochemical properties of HS-PG isolated from MP+ and MP- stromal cultures. HS-PG or isolated HS glycosaminoglycan (GAG) side chains partially blocked progenitor cell binding when they were added to the 2-hour binding phase of the BI-CFC or delta assays. Gel electrophoresis of HS-PG resolved more bands in matrix preparations from MP+ cultures than in preparations from MP- cultures. The blocking activity of the eluted MP+ HS-PG bands depended partly on the amount of GAG attached to the protein core and presumably partly on the structure of the core itself. Time course studies demonstrated that the HS-dependent phase of the binding interaction was limited to the first 30 to 60 minutes of the 2-hour binding phase. The different blocking effects of MP+ and MP- HS indicate that they have different biochemical properties. The HS-GAG in MP+ stroma has a higher degree of sulfation and a greater negative charge to mass ratio compared with MP- HS-GAG. Variations in HS may determine specific binding by hematopoietic progenitor cells and a heparan sulfate receptor is envisaged as acting in concert with further cell adhesion molecules (CAMs) on the progenitor cell surface.

scholarly journals Effects of recombinant alpha and gamma interferons on the in vitro growth of circulating hematopoietic progenitor cells (CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM) from patients with myelofibrosis with myeloid metaplasia

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1014-1019 ◽  
Author(s):  
C Carlo-Stella ◽  
M Cazzola ◽  
A Gasner ◽  
G Barosi ◽  
L Dezza ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cells ◽  
Definitive Treatment ◽  
Hematopoietic Progenitor Cell ◽  
In Vitro Growth ◽  
Hematopoietic Progenitor ◽  
Myeloid Metaplasia ◽  
Myelofibrosis With Myeloid Metaplasia

Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder due to clonal expansion of a pluripotent hematopoietic progenitor cell with secondary marrow fibrosis. No definitive treatment has as yet been devised for this condition, which shows a marked variability in clinical course. To evaluate whether excessive hematopoietic progenitor cell proliferation could be controlled by recombinant human interferon alpha (rIFN-alpha) and gamma (rIFN-gamma), we studied the effects of these agents on the in vitro growth of pluripotent and lineage-restricted circulating hematopoietic progenitor cells in 18 patients with MMM. A significant increase in the growth (mean +/- 1 SEM) per milliliter of peripheral blood of CFU-GEMM (594 +/- 253), CFU-Mk (1,033 +/- 410), BFU-E (4,799 +/- 2,020) and CFU- GM (5,438 +/- 2,505) was found in patients as compared with normal controls. Both rIFN-alpha and rIFN-gamma (10 to 10(4) U/mL) produced a significant dose-dependent suppression of CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM growth. Concentrations of rIFN-alpha and rIFN-gamma causing 50% inhibition of colony formation were 37 and 163 U/mL for CFU-GEMM, 16 and 69 U/mL for CFU-Mk, 53 and 146 U/mL for BFU-E, and 36 and 187 U/mL for CFU-GM, respectively. A marked synergistic effect was found between rIFN-alpha and rIFN-gamma: combination of the two agents produced inhibitory effects greater than or equivalent to those of 10- to 100- fold higher concentrations of single agents. These studies (a) confirm that circulating hematopoietic progenitors are markedly increased in MMM, (b) indicate that these presumably abnormal progenitors are normally responsive to rIFNs in vitro, and (c) show that IFNs act in a synergistic manner when used in combination. Because rIFN-gamma can downregulate collagen synthesis in vivo, this lymphokine could be particularly useful in the treatment of patients with MMM.

scholarly journals A novel 37-Kd adhesive membrane protein from cloned murine bone marrow stromal cells and cloned murine hematopoietic progenitor cells

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1436-1444 ◽  
Author(s):  
Y Shiota ◽  
JG Wilson ◽  
K Harjes ◽  
ED Zanjani ◽  
M Tavassoli
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Stromal Cell ◽  
Hematopoietic Cells ◽  
Marrow Stromal Cells ◽  
Hematopoietic Progenitor Cells ◽  
Single Chain ◽  
Hematopoietic Progenitor

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.

scholarly journals Human Mesenchymal Stem/Stromal Cells from Umbilical Cord Blood and Placenta Exhibit Similar Capacities to Promote Expansion of Hematopoietic Progenitor Cells In Vitro

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Guadalupe R. Fajardo-Orduña ◽  
Héctor Mayani ◽  
Patricia Flores-Guzmán ◽  
Eugenia Flores-Figueroa ◽  
Erika Hernández-Estévez ◽  
...  
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Stromal Cells ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Alternative Source

Mesenchymal stem/stromal cells (MSCs) from bone marrow (BM) have been used in coculture systems as a feeder layer for promoting the expansion of hematopoietic progenitor cells (HPCs) for hematopoietic cell transplantation. Because BM has some drawbacks, umbilical cord blood (UCB) and placenta (PL) have been proposed as possible alternative sources of MSCs. However, MSCs from UCB and PL sources have not been compared to determine which of these cell populations has the best capacity of promoting hematopoietic expansion. In this study, MSCs from UCB and PL were cultured under the same conditions to compare their capacities to support the expansion of HPCs in vitro. MSCs were cocultured with CD34+CD38−Lin− HPCs in the presence or absence of early acting cytokines. HPC expansion was analyzed through quantification of colony-forming cells (CFCs), long-term culture-initiating cells (LTC-ICs), and CD34+CD38−Lin− cells. MSCs from UCB and PL have similar capacities to increase HPC expansion, and this capacity is similar to that presented by BM-MSCs. Here, we are the first to determine that MSCs from UCB and PL have similar capacities to promote HPC expansion; however, PL is a better alternative source because MSCs can be obtained from a higher proportion of samples.

Chemotactic and chemokinetic activities of stem cell factor on murine hematopoietic progenitor cells

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4100-4108 ◽  
Author(s):  
N Okumura ◽  
K Tsuji ◽  
Y Ebihara ◽  
I Tanaka ◽  
N Sawai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Stem Cell Factor ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Murine Bone Marrow ◽  
Checkerboard Assay

We investigated the effects of stem cell factor (SCF) on the migration of murine bone marrow hematopoietic progenitor cells (HPC) in vitro using a modification of the checkerboard assay. Chemotactic and chemokinetic activities of SCF on HPC were evaluated by the numbers of HPC migrated on positive and negative gradients of SCF, respectively. On both positive and negative gradients of SCF, HPC began to migrate after 4 hours incubation, and their numbers then increased time- dependently. These results indicated that SCF functions as a chemotactic and chemokinetic agent for HPC. Analysis of types of colonies derived from the migrated HPC showed that SCF had chemotactic and chemokinetic effects on all types of HPC. When migrating activities of other cytokines were examined, interleukin (IL)-3 and IL-11 also affected the migration of HPC, but the degrees of each effect were lower than that of SCF. The results of the present study demonstrated that SCF is one of the most potent chemotactic and chemokinetic factors for HPC and suggest that SCF may play an important role in the flow of HPC into bone marrow where stromal cells constitutively produce SCF.

Aldehyde Dehydrogenase-Positive Hematopoetic Progenitor Cells in Peripheral Blood and Progenitor Cell Apheresis Products: Characterization and Correlation with Kinetics of Engraftment.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1076-1076
Author(s):  
Martin Hildebrandt ◽  
Markus Schuler ◽  
Kirstin Rautenberg ◽  
Christian Gerecke ◽  
Wolf-Dieter Ludwig
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
Progenitor Cell ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
Hematopoietic Progenitor Cells ◽  
High Dose ◽  
Hematopoietic Progenitor ◽  
Mantle Cell ◽  
Kinetics Of

Abstract Hematopoietic progenitor cells are rich in aldehyde dehydrogenase (ALDH) activity, allowing their identification using fluorogenic substrates (Aldefluor®, StemCo Biomedical, Durham, North Carolina) and Fluorescence-activated cell sorting (FACS). We compared the numbers of ALDH+ cells in peripheral blood and progenitor cell harvests with the numbers of CD34-positive cells. Furthermore, we compared the numbers of ALDH+ cells with the kinetics of hematopoietic engraftment following high-dose chemotherapy (HDCT) and transplantation of autologous stem cell harvests (SCT). 25 Patients (Multiple Myeloma, n=10, Hodgkin’s disease, n=3, mantle cell lymphoma, n=3, follicular lymphoma, n=2, T-cell lymphoma, n=3, Burkitt-like lymphoma, n=3) were included in treatment protocols involving high-dose chemotherapy, and received mobilization chemotherapy and G-CSF (10 μg/kg/d s.c.). The numbers of CD34-positive cells were determined daily, and peripheral blood progenitor cell apheresis was initiated when adequate. PBPC collections were performed on an AS 104 cell separator (Fresenius AG, St. Wendel, Germany). Samples of peripheral blood and of progenitor cell harvests were routinely tested for the numbers of CD34-positive cells and ALDH+ cells. The enrichment of CD34-positive cells was calculated and compared to the numbers of ALDH+ cells. 20 patients (Multiple Myeloma, n=10, Hodgkin’s disease, n=3, mantle cell lymphoma, n=3, follicular lymphoma, n=2, T-cell lymphoma, n=2) proceeded to HDCT followed by reinfusion of progenitor cell harvests. The enrichment of ALDH+ cells in the course of apheresis exceeded the enrichment of CD34-positive cells slightly (18,3fold +/−12,8 vs. 15,7fold +/−10,2). The percentage of CD34-negative cells among ALDH+ cells was comparable in peripheral blood and in the harvest, whereas the population of CD34-positive, ALDH−negative cells varied substantially in the peripheral blood (CD34−/ ALDH+: 7,53% +/−5,2% (pB) vs. 6,52% +/−3,9 (harvest); CD34+/ALDH−: 24,6% +/−12,3% (pB) vs. 11,9% +/−9,3% (harvest). Following HDCT and SCT, the numbers of ALDH+ cells and of CD34+ cells in the peripheral blood on the day of apheresis and in the harvests were compared with the reconstitution of the peripheral blood count. In a regression analysis, the number of ALDH+ cells in the peripheral blood on the day of apheresis (p=0,005), the number of ALDH+ cells transfused (p=0,01) and the number of CD34-positive cells transfused (p=0,012) were independent predictors of early recovery of the leukocyte counts. CD34-positive and ALDH+ cells appear to comprise partially different subsets of hematopoietic progenitor cells. The quantitation of ALDH+ cells may allow a more reliable prediction of the numbers of early hematopoietic progenitor cells than the assessment of CD34-positive cells and thus may be of predictive value for the recovery of leukocytes following SCT.

The Sialomucin CD164 (MGC-24v) Is an Adhesive Glycoprotein Expressed by Human Hematopoietic Progenitors and Bone Marrow Stromal Cells That Serves as a Potent Negative Regulator of Hematopoiesis

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2613-2628 ◽  
Author(s):  
Andrew C.W. Zannettino ◽  
Hans-Jörg Bühring ◽  
Silvana Niutta ◽  
Suzanne M. Watt ◽  
M. Ann Benton ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Surface ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Functional Characterization ◽  
Negative Regulator ◽  
Hematopoietic Progenitor Cells ◽  
Expression Cloning ◽  
Hematopoietic Progenitor

Mucin-like molecules represent an emerging family of cell surface glycoproteins expressed by cells of the hematopoietic system. We report the isolation of a cDNA clone that encodes a novel transmembrane isoform of the mucin-like glycoprotein MGC-24, expressed by both hematopoietic progenitor cells and elements of the bone marrow (BM) stroma. This molecule was clustered as CD164 at the recent workshop on human leukocyte differentiation antigens. CD164 was identified using a retroviral expression cloning strategy and two novel monoclonal antibody (MoAb) reagents, 103B2/9E10 and 105.A5. Both antibodies detected CD164/MGC-24v protein expression by BM stroma and subpopulations of the CD34+ cells, which include the majority of clonogenic myeloid (colony-forming unit–granulocyte-macrophage [CFU-GM]) and erythroid (blast-forming unit-erythroid [BFU-E]) progenitors and the hierarchically more primitive precursors (pre-CFU). Biochemical and functional characterization of CD164 showed that this protein represents a homodimeric molecule of approximately 160 kD. Functional studies demonstrate a role for CD164 in the adhesion of hematopoietic progenitor cells to BM stromal cells in vitro. Moreover, antibody ligation of CD164 on primitive hematopoietic progenitor cells characterized by the cell surface phenotype CD34BRIGHTCD38− results in the decreased recruitment of these cells into cell cycle, suggesting that CD164 represents a potent signaling molecule with the capacity to suppress hematopoietic cell proliferation. © 1998 by The American Society of Hematology.

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