RESUMEN

BACKGROUND: The function of hematopoietic stem cells (HSC) is regulated by HSC internal signaling pathways and their microenvironment. Chemokines and chemokine ligands play important roles in the regulation of HSC function. Yet, their functions in HSC are not fully understood. METHODS: We established Cxcr3 and Cxcl10 knockout mouse models (Cxcr3-/- and Cxcl10-/-) to analyze the roles of Cxcr3 or Cxcl10 in regulating HSC function. The cell cycle distribution of LT-HSC was assessed via flow cytometry. Cxcr3-/- and Cxcl10-/- stem/progenitor cells showed reduced self-renewal capacity as measured in serial transplantation assays. To study the effects of Cxcr3 or Cxcl10 deficient bone marrow microenvironment, we transplanted CD45.1 donor cells into Cxcr3-/-or Cxcl10-/- recipient mice (CD45.2) and examined donor-contributed hematopoiesis. RESULTS: Deficiency of Cxcl10 and its receptor Cxcr3 led to decreased BM cellularity in mice, with a significantly increased proportion of LT-HSC. Cxcl10-/- stem/progenitor cells showed reduced self-renewal capacity in the secondary transplantation assay. Notably, Cxcl10-/- donor-derived cells preferentially differentiated into B lymphocytes, with skewed myeloid differentiation ability. Meanwhile, Cxcr3-deficient HSCs demonstrated a reconstitution disadvantage in secondary transplantation, but the lineage bias was not significant. Interestingly, the absence of Cxcl10 or Cxcr3 in bone marrow microenvironment did not affect HSC function. CONCLUSIONS: The Cxcl10 and Cxcr3 regulate the function of HSC, including self-renewal and differentiation, adding to the understanding of the roles of chemokines in the regulation of HSC function.

Asunto(s)

Diferenciación Celular , Quimiocina CXCL10 , Células Madre Hematopoyéticas , Receptores CXCR3 , Animales , Receptores CXCR3/metabolismo , Receptores CXCR3/genética , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/genética , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/citología , Ratones , Ratones Noqueados , Ratones Endogámicos C57BL , Autorrenovación de las Células , Hematopoyesis , Trasplante de Células Madre Hematopoyéticas

RESUMEN

This paper presents the use of a magnetic manipulation device to remotely control the movement of Ag/Fe3O4 nanoparticles (NPs) for enhancing the antibacterial effect of Ag particles in aqueous suspensions containing Escherichia coli (E.coli). The Ag/Fe3O4 magnetic NPs were prepared by co-precipitation method where the Ag particles are simultaneously synthesized with the Fe3O4 particles to form Ag and Fe3O4 nanocomposite materials. The manipulation system utilized a homogeneous rotating magnetic field to carry out magnetic stirring of NPs in the petri dishes containing bacterial suspensions. The optimum magnetron parameters and best antibacterial effects were implemented with six different concentrations from 0.6 wt % to 6.6 wt % of the NPs at driving frequencies from 50 rpm to 200 rpm for 3 min. The highest antibacterial effect of 99.4% was achieved at 5.4 wt % of NPs and the driving frequency of 100 rpm. A time-dependent antibacterial effect in 0.1 wt % of Ag/Fe3O4 was also observed. The results indicate that the use of specific rotating magnetic fields to manipulate Ag/Fe3O4 magnetic NPs can significantly improve the antibacterial efficacy. Due to the good biocompatibility of the Ag NPs, the presented technique can be applied to clean water resources in the future.