Adaptation of Human iPSC-Derived Macrophages Toward an Alveolar Macrophage-Like Phenotype Post-Intra-Pulmonary Transfer into Murine Models

Alveolar macrophages (AMs) represent crucial immune cells in the bronchioalveolar space of the lungLungs. Given the important role in the host defense machinery and lungLungs tissue homeostasis, AMs have been linked to a variety of diseases and thus represent a promising target cell type for novel therapies. The emerging importance of AMAlveolar macrophage (AM) underlines the necessity to isolate and/or generate proper cellular models, which facilitate basic biology and translational science. As of yet, most studies focus on the derivation of AMAlveolar macrophage (AM) from the murine system. This chapter introduces the use of human-induced pluripotent stem cellInduced pluripotent stem cell (iPSC) (iPSCInduced pluripotent stem cell (iPSC))-derived primitive macrophages, which can be further matured towards an AM-like phenotype upon intra-pulmonary transferIntra-pulmonary transfer into mice. We will give a brief overview on the generation of primitive iPSC-derived macrophages, which is followed by a detailed, step-by-step description of the intra-pulmonary transferIntra-pulmonary transfer of cells and the follow-up procedures needed to isolate the iPSC-derived, AM-like cells from the lungsLungs post-transfer. The chapter provides an alternative approach to derive human AM-like cells, which can be used to study human AMAlveolar macrophage (AM) biology and to investigate novel therapeutic interventions using primitive macrophages from iPSCInduced pluripotent stem cell (iPSC).