The human hematopoietic stem cell compartment is heterogeneous for CXCR4 expression

Abstract

The chemokine stromal derived factor-1␣ (SDF-1␣) has been implicated recently in the chemotaxis of primitive human hematopoietic cells, suggesting that pluripotent human stem cells express the SDF-1␣ receptor, CXCR4. By using flow cytometry and confocal microscopy, we have identified and isolated primitive subsets of human CXCR4 ؉ and CXCR4 ؊ cells. Distinctions in the progenitor content and response to SDF-1␣ in vitro indicate that CXCR4 ؉ and CXCR4 ؊ cells represent discrete populations of primitive blood cells. The i.v. transplantation of these subfractions into immune-deficient mice established that both possess comparable engraftment capacity in vivo. Human myeloid, lymphoid, and primitive CD34 ؉ CXCR4 ؉ cells were present in chimeric animals transplanted with either subset, indicating that CXCR4 ؉ and CXCR4 ؊ stem cells have equivalent proliferative and differentiative abilities. Our study indicates that the human stem cell compartment is heterogeneous for CXCR4 expression, suggesting that the relationship between CXCR4 expression and stem cell repopulating function is not obligatory.stromal-derived factor-1␣ ͉ xenotransplantation

The role of G-protein signaling in hematopoietic stem/progenitor cell mobilization

“…[24][25][26] Whether in vivo treatments with polyclonal antibodies versus different CXCR4 antagonistic molecules with potentially different modes of action could account for these differences is difficult to discern at this point and further experimentation is warranted. On a relevant vein, data with in vitro anti-CXCR4 antibody treatments are inconsistent [61][62][63][64] and at odds with studies using Ptx-treated cells in homing experiments of murine BM, 60 murine fetal liver cells, 65 or human CD34 ϩ cells. 62 Collectively, the weight of the evidence suggests that CXCR4/SDF-1 signaling may not be crucial for the initial anchoring of transplanted cells to endothelial cells within BM, but their subsequent retention within BM is greatly dependent on CXCR4/SDF-1 signaling.…”

Stromal support augments extended long-term ex vivo expansion of hemopoietic progenitor cells

“…A study by Peled et al showed that the chemokine stromal cell derived factor (SDF)-1 and its receptor CXCR4, which is expressed on some CD34 + CD38 − cells amongst others, may be important for engraftment of sublethally irradiated NOD/SCID mice, although there is evidence that CXCR4 is heterogeneously expressed on SRC. 31,52 The cytokines SCF and IL6 induced CXCR4 up-regulation on CD34 + cells, which subsequently potentiated migration of these precursor cells and their engraftment in primary and secondary transplanted mice. Thus, the use of at least SCF +/− IL6 in the present study might have caused increased homing potential of the CD34 + UCB cells in 2-week cultures, which in turn contributed to the increased SRA.…”

Introduction

“…Dr Tsvee Lapidot will contribute a mini-review on the interesting work done in his laboratory on SDF-1 activation of the CXCR4 homing receptor, thought in previous years to be most important on T cells as the co-receptor for the HIV virus. Although somewhat controversial, 31 the work of Dr Lapidot and others has shown that the CXCR4 receptor plays an additional role in the in vivo homing and engraftment of stem cells. 32,33 Another exciting area of research in the stem cell homing area is discussed in this issue by Ed Srour, who along with Peter Quesenberry and Pamela Becker's groups, have shown that non-cycling hematopoietic stem cells home back to the bone marrow more efficiently than cycling cells.…”