NOD/SCID repopulating cells but not LTC-IC are enriched in human CD34+ cells expressing the CCR1 chemokine receptor

Abstract

Human haemopoietic stem and progenitor cells may be distinguished by the pattern of cell surface markers they display. The cells defined as 'stem' cells are heterogeneous and lack specific markers for their detection. However, they may be identified in in vitro assays such as the long-term culture initiating cell (LTC-IC) and in transplant assays involving immunosuppressed NOD/SCID mice. It is still not clear to what extent, if any, these cell populations overlap. The chemokine macrophage inflammatory protein-1␣ (MIP-1␣) prolongs survival of LTC-IC in suspension cultures and we now show that in longterm bone marrow cultures (LTBMC) maintenance of haemopoiesis was significantly better from the CD34 + cells which possess MIP-1␣ receptors (P Ͻ 0.006). We examined one MIP-1␣ receptor, CCR1, which is present on CD34 ؉ cells from haemopoietic tissues. In LTBMC the production of GM-CFC from CD34 ؉ CCR1 ؊ cells was significantly higher (P Ͻ 0.02) than that from CD34 ؉ CCR1 ؉ cultures and the incidence of LTC-IC was 3-to 6-fold higher in the CD34 ؉ CCR1 ؊ cell fraction. In contrast, the cells responsible for high levels of engraftment in NOD/SCID mice were contained in the CD34 ؉ CCR1 ؉ cell fraction. The CD34 ؉ CCR1 ؉ cells engrafted to high levels in NOD/SCID and generated large numbers of progenitor cells. Therefore, we conclude that LTC-IC and SRC may be distinguished on the basis of expression of the chemokine receptor CCR1. Leukemia (2001) 15, 1092-1101.

MIP-1α/CCL3-expressing basophil-lineage cells drive the leukemic hematopoiesis of chronic myeloid leukemia in mice

“…14,15 However, unlike normal HSCs, LICs are resistant to the inhibitory effects of CCL3 on in vitro proliferation. 12,13 Wark et al previously revealed that forced activation of Abl tyrosine kinase in a human HSC cell line can directly depress the CCL3-mediated increase in cytosolic Ca 21 concentration without any changes in the expression of CCL3 receptors. 11 In contrast, our group and others observed that the expression of CCL3 receptors, especially CCR5, decreased in CML progenitor cells.…”

“…12,17,20,21 The competitive BM transplantation assay demonstrated that the ablation of CCR1 or CCR5 in donor cells resulted in a higher chimerism of WBC and BM KLS 1 cells after serial BM transplantations (supplemental Figure 4A-B). In addition, an increased proportion of donor-derived WBCs in PB was evident even until 40 weeks after the primary BM transplantation with CCR5 2/2 donor-derived cells (supplemental Figure 5).…”

The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review

“…In mice, knocking out (CXCR2) delayed hematopoietic recovery [134]. On the other hand, CCR1 expression marked human HSC as responsible for high levels of xeno-engraftment in mice [135]. These are some examples of the contribution of chemokines to hematopoietic-niche integrity.…”

The human chorion contains definitive hematopoietic stem cells from the fifteenth week of gestation

“…CXCR7, another CXCL12 receptor (Tarnowski et al, 2010), cooperates with CD184 in enhancing the effects of CXCL12 on cell cycling, survival and proliferation of CD34 + cells from peripheral blood (Torossian et al, 2014). In addition, CD34 + cells from umbilical cord blood express CD193 (Lamkhioued et al, 2003), and CD191 expression by CD34 + cells in cord blood confers superior engraftment of immunodeficient mice (de Wynter et al, 2001 .…”