458653 Human Stem Cell Derived Neutrophils As a Primary Neutrophil Model
In order to properly model primary human neutrophils, hiPSC-derived neutrophils must display the same morphology, migration, and anti-microbial behavior as primary human neutrophils. We have found that the morphology of hiPSC-derived neutrophils is indistinguishable from primary human neutrophils. Furthermore, hiPSC-derived neutrophils have the characteristic tri-lobed nucleus common to primary neutrophils. In order to reach sites of inflammation neutrophils must be capable of migrating to known neutrophil chemoattractants. We studied neutrophil chemotaxis using a previously published microfluidic device that creates a stable chemokine gradient and found that hiPSC-derived neutrophils efficiently chemotax to a source of the bacterial peptide fMLP, a common neutrophil chemoattractant. Finally, hiPSC-derived neutrophils must be able to perform anti-microbial functions. We visualized hiPSC-derived neutrophils in co-culture with pseudomonas aeruginosa using time-lapse microscopy. In contrast to popular neutrophil cell lines that lack the ability to phagocytose bacteria, we found that hiPSC-derived neutrophils were capable of efficiently phagocytosing pseudomonas over an extended period of time. We have also found that, upon activation, hiPSC-derived neutrophils produce neutrophil extracellular traps, proving these cells are capable of performing several anti-microbial functions.
Overall, we have found that hiPSC-derived neutrophils accurately recapitulate many characteristics and can serve as an excellent model of primary human neutrophils. We have shown that hiPSC-derived neutrophils share the morphology, migration capabilities, and anti-microbial functions of primary human neutrophils. hiPSC-derived neutrophils have the characteristic tri-lobed nuclei, are capable of chemotaxis to fMLP, a physiologically relevant chemokine, and poses the ability to phagocytose bacteria. In the future, hiPSC-derived neutrophils as a model will allow for more in-depth study of primary human neutrophil function.