Study on the mechanism of enhancing homing efficiency of human hematopoietic stem/progenitor cells into bone marrow after manipulation with tumor necrosis factor alpha in xenotransplanted BALB/c mouse model / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the role of tumor necrosis factor (TNF) alpha on the homing efficiency of hematopoietic stem/progenitor cells (HS/PC) into bone marrow and its mechanism.</p><p><b>METHODS</b>CFSE-labeled umbilical cord blood (UCB) CD34+ cells were transplanted into irradiated (control group) or combined with TNF alpha prepared (experimental group) BALB/c recipient mice. The distribution in peripheral blood, liver, lung and homing characteristics in bone marrow and spleen of UCB CD34+ cells, in BALB/c recipient mice were determined 20 hours after xenotransplantation by flow cytometry (FACS) and their homing efficiency was calculated. ELISA was used to measure serum SDF-1 alpha level. CXCR4 expression levels of on UCB CD34+ cells were assessed by FACS pre-/post-manipulation with TNF alpha. SDF-1 alpha expression level in bone marrow and spleen was tested by immunohistochemistry.</p><p><b>RESULTS</b>UCB CD34+ cells mainly home into recipient mice bone marrow and spleen; The homing efficiency in experimental group bone marrow [(0.65 +/- 0.13)%] was significantly higher than that in control ones [(0.30 +/- 0.09)%, P < 0.01], whereas the homing efficiency in experimental group spleen was dramatically lower than that in control ones (P < 0.01); Treatment with TNF alpha did not affect recipient serum SDF-1 alpha level; After 18 hours co-cultured with TNF alpha, the CXCR4e expression level on UCB CD34+ cells was similar to that on fresh ones; TNF alpha treatment induced significantly higher SDF-1 alpha expression on osteoblastic and stromal cells in bone marrow, and reversed spleen SDF-1 alpha gradient that was originally favorable for CD34+ cells homing.</p><p><b>CONCLUSION</b>TNF alpha enhances the homing efficiency of HS/PC via up-regulating SDF-1 alpha gradient in bone marrow, and might be an useful enhancer for HS/PC homing in clinical practice.</p>

Surface-modified paclitaxel-loaded nanoparticles as local delivery system for the prevention of vessel restenosis / 药学学报

The novel paclitaxel-loaded nanopaticle through surface modification with didodecylmethylammonium bromide (DMAB) was prepared and its prevenative against neointimal formation in a rabbit carotid artery injury model was tested. Paclitaxel-loaded nanoparticles were prepared from oil-water emulsions using biodegradable poly (lactic acid-co-glycolic acid) (PLGA). Specific additive for surface conjugation was added after particle formation. To enhance arterial retention using a cationic surfactant, DMAB, was used. The size and distribution, surface morphology and surface charge of the paclitaxel-loaded nanoparticles were then investigated by laser light scattering, scanning electron microscope and zeta potential analyzer. The drug encapsulation efficiency (EE) and in vitro release profile were measured by high-performance liquid chromatography (HPLC). Balloon injured rabbit carotid arteries were treated with single infusion of the paclitaxel-loaded NP suspension and observed for 28 days. The inhibitory effects of vascular smooth muscle cell migration and proliferation were evaluated as end-point. The NPs showed spherical shape with diameter ranging from 200 to 500 nm. The negatively charged PLGA NPs shifted to positive after the DMAB modification. The in vitro drug release profile showed a triphasic release pattern. 28 days later, morphologic analysis revealed that the inhibitory effect of intima proliferation is dose-dependent, and the 30 mg x mL(-1) nanoparticle concentration suspension could completely inhibit proliferation of intima. Paclitaxel-loaded nanoparticles through surface modification with DMAB provide an effective means of inhibiting proliferation response to vascular injury in the rabbit.