Abstract: Sickle cell disease (SCD) is a single gene disorder characterized by mutant hemoglobin-S(HbS) and chronic intravascular haemolysis. Painful vaso-occlusive crises (VOC) are typical of SCD and often associated to a further rise in hemolysis. VOC is the clinically painful form of vaso-occlusion, that is due to the aggregation of red blood cells in the capillaries and venules. Such event is promoted or aggravated by adhesion of polymorphonuclear neutrophils (PMNs) to red blood cells and the endothelium leading to tissue ischemia, inflammation and imperfect repair. Repeated vaso-occlusion and PMNs interactions with the vascular endothelium are thought to promote microvascular injuries in SCD patients. The inventors tested the effect of pharmacological inhibition of TREM-1 with LR12 peptide in two experimental vaso-occlusive crisis models. Additional validation of TREM-1 involvement in vaso-occlusion was verified using mice with sickle cell disease and Trem-1 gene deficiency.

Abstract: The present invention relates to a method for obtaining Ngn3-expressing cells and insulin producing-beta cells by contacting a Pdx1-expressing pancreas explant with an amount of at least one histone deacetylase inhibitor (HDACi). The inventive methods have the advantage of being simple and quick, and of providing large amounts of Ngn3-expressing cells and insulin producing-beta cells, that are useful therapeutic tools. The invention also relates to a pharmaceutical composition for the treatment of diabetes which comprises an amount of at least one HDACi.