Modelling CLL cell and T-cell Migration in a Dynamic Circulating Model of CLL
Poster Apr 21, 2015
Elisabeth Walsbyl, Paul Brennan', Guy Pratte, Andrea Buggins3, Tanja N Hartmann'', Chris Fegan1 and Chris Pepper'
We have recently developed a novel circulating model of chronic lymphocytic leukaemia (CLL) that mimics the transient interactions that take place between circulating lymphocytes and vascular endothelium. Here we show that both normal and malignant lymphocytes actively underwent transendothelial migration. Furthermore, seeding of CXCL12-secreting MRC5 cells into the extravascular space (EVS) resulting in significantly enhanced CLL cell migration (P = 0.024) but no increase in T-cell migration. Both CLL cells and T-cells recovered from the EVS showed evidence of activation markers and entry into cell cycle as demonstrated by increased Ki-67 expression (P<0.0001). We subsequently established that CLL cell Ki-67 expression was dependent on the presence of T-cells, as depletion of the T-cells from the circulating compartment significantly inhibited Ki-67 induction (P = 0.003). It is worthy of note that as a proportion of all circulating peripheral blood mononuclear cells, CD3+ T-cells migrated significantly more than CD19+ CLL cells (P = 0.02). This seems likely to be promoted by CLL cell secretion of T-cell attracting chemokines CCL3 (298pg/m1±197.5) and CCL4 (56pg/m1±115.6) in our model. Interestingly, CD38+ CLL samples showed elevated levels of CCL3 and CCL4 suggesting that increased T-cell recruitment may contribute to the inferior clinical outcomes seen in these patients. Taken together the data presented here highlight the requirement of T-cells in the pathology of CLL.
Extracorporeal shockwave therapy accelerates motor axon regeneration despite a phenotypically mismatched environmentPoster
A femoral nerve defect model was adapted for the evaluation of proregenerative effects of extracorporeal shockwave therapy (ESWT). Functional evaluation, histology and qRT-PCR data show differences between sensory and motor-derived nerve transplants and a pro-regenerative effect of ESWT. These data provide evidence for the clinical application of ESWT after autologous nerve transplantation as a novel non-invasive method.READ MORE
Cerebral Malaria Insights: Pathogenesis, Host Parasite Interactions including Host ResistancePoster
Cerebral malaria is a dreadful disease transmitted by mosquito. The major preventive approach is focused more in vector control than development of anti-malarial drug. The purpose of this presentation is to analyze different aspects of disease manifestations including clinical symptoms and pathogenesis in the context of mosquito borne infections in different geographical regions of the world.READ MORE