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

Abstract

Alveolar macrophages (AMs) represent crucial immune cells in the bronchioalveolar space of the lung. Given the important role in the host defense machinery and lung 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 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 AM from the murine system. This chapter introduces the use of human-induced pluripotent stem cell (iPSC)-derived primitive macrophages, which can be further matured towards an AM-like phenotype upon intra-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 transfer of cells and the follow-up procedures needed to isolate the iPSC-derived, AM-like cells from the lungs post-transfer. The chapter provides an alternative approach to derive human AM-like cells, which can be used to study human AM biology and to investigate novel therapeutic interventions using primitive macrophages from iPSC.

Keywords: Alveolar macrophages; Hematopoietic differentiation; Induced pluripotent stem cells; Intrapulmonary transfer; Lung; Macrophages; PMT; iPSC.