OBJECTIVE: Stromal cell-derived factor-1alpha (SDF-1alpha) has been implicated in homing and engraftment of primitive hematopoietic progenitor cells (HPC) in studies demonstrating reduced NOD/SCID repopulating potential of HPC exposed to supra-physiologic concentrations of SDF-1alpha or anti-CXCR4. Outcome of CXCR4 signaling in some cells has been shown to be dependent on the concentration of SDF-1alpha. We aimed to determine whether similar concentration-dependent responses to CXCR4 signaling are present in CD34(+)cells. MATERIALS AND METHODS: Human peripheral blood (PB), mobilized PB (MPB), or bone marrow (BM) CD34(+) cells were incubated for 30 minutes with different concentrations of SDF-1alpha or anti-CXCR4, washed, then assessed for in vitro hematopoietic potential, migration, and NOD/SCID repopulating potential. RESULTS: Exposure of MPB or PB CD34(+) cells to 100 ng/mL SDF-1alpha increased tyrosine phosphorylation without subsequent proliferation or apoptosis. Spontaneous and SDF-1alpha-directed migration also increased in pretreated cells, despite previous exposure to SDF-1alpha. Cells exposed to 1 microg anti-CXCR4/10(6) cells displayed similar increases in activation and migration as cells exposed to SDF-1alpha, demonstrating the ability of anti-CXCR4 to activate the CXCR4 receptor. Interestingly, chimerism in NOD/SCID mice transplanted with MPB CD34(+) cells pretreated with SDF-1alpha or anti-CXCR4 was increased, while exposure of these cells to 10- to 100-fold higher concentrations of these proteins inhibited in vitro migration and NOD/SCID repopulating potential. Migration and NOD/SCID repopulating potential of BM CD34(+) cells remained unchanged after treatment with either protein. CONCLUSIONS: These results illustrate the ability of SDF-1alpha and anti-CXCR4 to augment repopulating potential of CD34(+) cells, and suggest that HPC function can be favorably modulated through specific CXCR4 signaling.
OBJECTIVE: Stromal cell-derived factor-1alpha (SDF-1alpha) has been implicated in homing and engraftment of primitive hematopoietic progenitor cells (HPC) in studies demonstrating reduced NOD/SCID repopulating potential of HPC exposed to supra-physiologic concentrations of SDF-1alpha or anti-CXCR4. Outcome of CXCR4 signaling in some cells has been shown to be dependent on the concentration of SDF-1alpha. We aimed to determine whether similar concentration-dependent responses to CXCR4 signaling are present in CD34(+)cells. MATERIALS AND METHODS:Human peripheral blood (PB), mobilized PB (MPB), or bone marrow (BM) CD34(+) cells were incubated for 30 minutes with different concentrations of SDF-1alpha or anti-CXCR4, washed, then assessed for in vitro hematopoietic potential, migration, and NOD/SCID repopulating potential. RESULTS: Exposure of MPB or PB CD34(+) cells to 100 ng/mL SDF-1alpha increased tyrosine phosphorylation without subsequent proliferation or apoptosis. Spontaneous and SDF-1alpha-directed migration also increased in pretreated cells, despite previous exposure to SDF-1alpha. Cells exposed to 1 microg anti-CXCR4/10(6) cells displayed similar increases in activation and migration as cells exposed to SDF-1alpha, demonstrating the ability of anti-CXCR4 to activate the CXCR4 receptor. Interestingly, chimerism in NOD/SCIDmice transplanted with MPB CD34(+) cells pretreated with SDF-1alpha or anti-CXCR4 was increased, while exposure of these cells to 10- to 100-fold higher concentrations of these proteins inhibited in vitro migration and NOD/SCID repopulating potential. Migration and NOD/SCID repopulating potential of BM CD34(+) cells remained unchanged after treatment with either protein. CONCLUSIONS: These results illustrate the ability of SDF-1alpha and anti-CXCR4 to augment repopulating potential of CD34(+) cells, and suggest that HPC function can be favorably modulated through specific CXCR4 signaling.
Authors: Jodi L Murakami; Baohui Xu; Christopher B Franco; Xingbin Hu; Stephen J Galli; Irving L Weissman; Ching-Cheng Chen Journal: Stem Cells Dev Date: 2015-11-05 Impact factor: 3.272
Authors: Douglas R Kennedy; Kyle McLellan; Peter F Moore; Paula S Henthorn; Peter J Felsburg Journal: Biol Blood Marrow Transplant Date: 2009-06 Impact factor: 5.742
Authors: Hal E Broxmeyer; Christie M Orschell; D Wade Clapp; Giao Hangoc; Scott Cooper; P Artur Plett; W Conrad Liles; Xiaxin Li; Barbara Graham-Evans; Timothy B Campbell; Gary Calandra; Gary Bridger; David C Dale; Edward F Srour Journal: J Exp Med Date: 2005-04-18 Impact factor: 14.307