The 2019 AACR (American Association for Cancer Research) Annual Meeting is approaching, in fact, it will be held on March 29-April 4 in Atlanta, USA,and you might consider attending this congress. There, you might find this article a good subject for discussion when mingling with your colleagues.
We are also pleased to provide you with our booklets, about Small Molecules in Stem Cell and Cellular reprograming Research, which we hope will be useful to you and your colleagues.
Bacterial and fungal infections are a major cause of morbidity and mortality in neutropenic patients. Donor-derived neutrophil transfusions have been used for prophylaxis or treatment foran infection in neutropenic patients. However, the short half-life and the limited availability of large numbers of donor-derived neutrophils for transfusion remain a significant hurdle in the implementation of neutrophil transfusion therapy. Here, we investigate the in vitro and in vivo activity of neutrophils generated from human induced pluripotent stem cells (iPSC), a potentially unlimited resource to produce neutrophils for transfusion. Phenotypic analysis of iPSC derived neutrophils reveal reactive oxygen species production at similar or slightly higher than normal peripheral blood neutrophils, but have an ~50%–70% reduced Escherichia coli phagocytosis and phorbol 12-myristate 13-acetate induced formation of neutrophil extracellular traps (NET). Signaling of granulocytic precursors identified impaired AKT activation, but not ERK or STAT3, in agonist-stimulated iPSC derived neutrophils. Expression of a constitutively activated AKT in iPSC derived neutrophils restores most phagocytic activity and NET formation. In a model of bacterial-induced peritonitis in immunodeficient mice, iPSC derived neutrophils, with or without corrected AKT activation, migrate similarly to the peritoneal fluid as peripheral blood neutrophils, whereas the expression of activated AKT significantly improves their phagocytic activity in vivo.