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The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood.

Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC - J. Exp. Med. (1997)

Bottom Line: This is the first chemoattractant reported for human CD34+ progenitor cells.Concentrations of SDF-1 that elicit chemotaxis also induce a transient elevation of cytoplasmic calcium in CD34+ cells.CD34+ cells migrating to SDF-1 include cells with a more primitive (CD34+/CD38- or CD34+/DR-) phenotype as well as CD34+ cells phenotypically committed to the erythroid, lymphoid and myeloid lineages, including functional BFU-E, CFU-GM, and CFU-MIX progenitors.

View Article: PubMed Central - PubMed

Affiliation: Center for Blood Research, Inc., Boston, Massachusetts, USA.

ABSTRACT
Hematopoietic progenitor cells migrate in vitro and in vivo towards a gradient of the chemotactic factor stromal cell-derived factor-1 (SDF-1) produced by stromal cells. This is the first chemoattractant reported for human CD34+ progenitor cells. Concentrations of SDF-1 that elicit chemotaxis also induce a transient elevation of cytoplasmic calcium in CD34+ cells. SDF-1-induced chemotaxis is inhibited by pertussis toxin, suggesting that its signaling in CD34+ cells is mediated by seven transmembrane receptors coupled to Gi proteins. CD34+ cells migrating to SDF-1 include cells with a more primitive (CD34+/CD38- or CD34+/DR-) phenotype as well as CD34+ cells phenotypically committed to the erythroid, lymphoid and myeloid lineages, including functional BFU-E, CFU-GM, and CFU-MIX progenitors. Chemotaxis of CD34+ cells in response to SDF-1 is increased by IL-3 in vitro and is lower in CD34+ progenitors from peripheral blood than in CD34+ progenitors from bone marrow, suggesting that an altered response to SDF-1 may be associated with CD34 progenitor mobilization.

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BM stromal cells produce a chemoattractant for human  CD34+ progenitor cells. CD34+ cells from human cord blood (CB) (2.0 ×  105/well) were assayed for their capacity to migrate in a Boyden chamber  (5 μm bare filters), towards conditioned media from different BM stromal  cell lines. The migratory population was evaluated phenotypically as the  number of CD34+ cells that migrated (left, open bars), and functionally as  the number of clonogenic progenitors (CFC) that migrated to the conditioned media (right, closed bars). Bars and columns indicate the duplicate  and mean of one representative experiment out of three.
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Figure 1: BM stromal cells produce a chemoattractant for human CD34+ progenitor cells. CD34+ cells from human cord blood (CB) (2.0 × 105/well) were assayed for their capacity to migrate in a Boyden chamber (5 μm bare filters), towards conditioned media from different BM stromal cell lines. The migratory population was evaluated phenotypically as the number of CD34+ cells that migrated (left, open bars), and functionally as the number of clonogenic progenitors (CFC) that migrated to the conditioned media (right, closed bars). Bars and columns indicate the duplicate and mean of one representative experiment out of three.

Mentions: We have used an in vitro chemotactic assay to study the migratory response of human CD34+ progenitor cells to different stimuli. Since cells of the microenvironment of the BM may be involved in the trafficking of HPC, we first assayed the chemotactic response of CD34+ cells to conditioned media from different BM stromal cell lines. Conditioned media from MS-5 stromal cells (22) and, to a lesser extent, from other BM stromal cell lines (16), were able to induce the chemotaxis in vitro of human CD34+ progenitor cells (Fig. 1). Migratory cells were evaluated both phenotypically by the expression of CD34 and functionally by their ability to form hematopoietic colonies in methylcellulose assays (CFC).


The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood.

Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC - J. Exp. Med. (1997)

BM stromal cells produce a chemoattractant for human  CD34+ progenitor cells. CD34+ cells from human cord blood (CB) (2.0 ×  105/well) were assayed for their capacity to migrate in a Boyden chamber  (5 μm bare filters), towards conditioned media from different BM stromal  cell lines. The migratory population was evaluated phenotypically as the  number of CD34+ cells that migrated (left, open bars), and functionally as  the number of clonogenic progenitors (CFC) that migrated to the conditioned media (right, closed bars). Bars and columns indicate the duplicate  and mean of one representative experiment out of three.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196104&req=5

Figure 1: BM stromal cells produce a chemoattractant for human CD34+ progenitor cells. CD34+ cells from human cord blood (CB) (2.0 × 105/well) were assayed for their capacity to migrate in a Boyden chamber (5 μm bare filters), towards conditioned media from different BM stromal cell lines. The migratory population was evaluated phenotypically as the number of CD34+ cells that migrated (left, open bars), and functionally as the number of clonogenic progenitors (CFC) that migrated to the conditioned media (right, closed bars). Bars and columns indicate the duplicate and mean of one representative experiment out of three.
Mentions: We have used an in vitro chemotactic assay to study the migratory response of human CD34+ progenitor cells to different stimuli. Since cells of the microenvironment of the BM may be involved in the trafficking of HPC, we first assayed the chemotactic response of CD34+ cells to conditioned media from different BM stromal cell lines. Conditioned media from MS-5 stromal cells (22) and, to a lesser extent, from other BM stromal cell lines (16), were able to induce the chemotaxis in vitro of human CD34+ progenitor cells (Fig. 1). Migratory cells were evaluated both phenotypically by the expression of CD34 and functionally by their ability to form hematopoietic colonies in methylcellulose assays (CFC).

Bottom Line: This is the first chemoattractant reported for human CD34+ progenitor cells.Concentrations of SDF-1 that elicit chemotaxis also induce a transient elevation of cytoplasmic calcium in CD34+ cells.CD34+ cells migrating to SDF-1 include cells with a more primitive (CD34+/CD38- or CD34+/DR-) phenotype as well as CD34+ cells phenotypically committed to the erythroid, lymphoid and myeloid lineages, including functional BFU-E, CFU-GM, and CFU-MIX progenitors.

View Article: PubMed Central - PubMed

Affiliation: Center for Blood Research, Inc., Boston, Massachusetts, USA.

ABSTRACT
Hematopoietic progenitor cells migrate in vitro and in vivo towards a gradient of the chemotactic factor stromal cell-derived factor-1 (SDF-1) produced by stromal cells. This is the first chemoattractant reported for human CD34+ progenitor cells. Concentrations of SDF-1 that elicit chemotaxis also induce a transient elevation of cytoplasmic calcium in CD34+ cells. SDF-1-induced chemotaxis is inhibited by pertussis toxin, suggesting that its signaling in CD34+ cells is mediated by seven transmembrane receptors coupled to Gi proteins. CD34+ cells migrating to SDF-1 include cells with a more primitive (CD34+/CD38- or CD34+/DR-) phenotype as well as CD34+ cells phenotypically committed to the erythroid, lymphoid and myeloid lineages, including functional BFU-E, CFU-GM, and CFU-MIX progenitors. Chemotaxis of CD34+ cells in response to SDF-1 is increased by IL-3 in vitro and is lower in CD34+ progenitors from peripheral blood than in CD34+ progenitors from bone marrow, suggesting that an altered response to SDF-1 may be associated with CD34 progenitor mobilization.

Show MeSH
Related in: MedlinePlus