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

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.

Hepatocyte growth factor/scatter factor (HGF/SF) affects proliferation and migration of myeloid leukemic cells

“…Three of five MDS patients and 5/7 AML patients showed a marked migration in response to HGF/SF. Supernatant of BM stromal cells, which contains a strong chemoattractant (SDF-1) for hemopoietic progenitor cells, was superior to HGF/SF in inducing migration 61,62 (Table 4). The chemoattractive property of BM stroma supernatant was partially reversed by the addition of a neutralizing monoclonal antibody directed to HGF/SF, suggesting that HGF/SF, which is present in supernatant of BM stromal cells (approximately 1-2 ng/ml; 27 ), is at least partly responsible for the migration promoting effect.…”

Invasive characteristics of human prostatic epithelial cells: understanding the metastatic process

“…The key molecular axis for this homing has been shown to involve the CXC chemokine stromal-derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 (CD186). This model is supported by the facts that both bone marrow endothelial cells and osteoblasts express SDF-1 (Aiuti et al, 1997;Hamada et al, 1998;Ponomaryov et al, 2000), CXCR4 knockouts do not show haematopoietic engraftment of the bone marrow (Aiuti et al, 1999) and that the level of CXCR4 expression by HSC determines their ability to engraft the bone marrow (Peled et al, 1999). It has been shown recently that the CXCR4/CXCL12 axis also plays a crucial role in the targeting of several solid tumour metastases, including breast (Muller et al, 2001) kidney (Staller et al, 2003), lung (Burger et al, 2003), pancreas (Koshiba et al, 2000) and CaP (Taichman et al, 2002;Sun et al, 2003) to the bone marrow.…”

The niche of stellate cells within rat liver

“…20,21 The SDF-1/CXCR4 axis plays an essential role in directing hematopoietic stem cells along a SDF1 gradient to their final niche in the bone marrow during ontogenesis, 22 but also in their mobilization into the peripheral blood. 23 Stem cell niches are further innervated by the sympathetic nervous system, which is involved in regulation of hematopoietic stem cell recruitment. 24 The recruitment of stem cells from the bone marrow is at least in part mediated by local downregulation of SDF1 that facilitates the release of stem cells into the blood stream.…”