Macrophages from human pluripotent stem cells
Cowley SA., Karlsson KR., van Wilgenburg B., Carter GC., Browne C., Vowles J., Estrada FM., Pelchen-Matthews A., Miller J., Moore MD., James W.
We have previously developed a relatively simple, feeder-free method for deriving monocytes and macrophages from human Embryonic Stem cells, enabling the routine harvest of batches of up to 107 homogeneous monocytes from culture supernatants from a single standard 6-well tissue culture plate. Here we demonstrate further functional characteristics of these stem cell-derived macrophages. They are infectable with various strains of HIV-1, with appropriate replication kinetics, making them an attractive source of cells for studying HIV-macrophage interactions. They are also infectable with an important arbovirus, dengue virus. They suppress T cell proliferation, with tryptophan catabolism implicated in the process. We describe methods for genetically modifying the stem cells to maximise expression of genes-of-interest in the differentiated macrophages, addressing potential issues of transgene silencing transgene during differentiation. We also show that the method can be used to differentiate monocytes/ and macrophages from human induced Pluripotent Stem cells. This provides an accessible, reproducible, tractable system for investigating macrophage biology and host-pathogen interactions against known patient and control genetic backgrounds. © 2012 by Nova Science Publishers, Inc. All Rights Reserved.