Induced pluripotent stem cell derived macrophages differentiate into AM like cells in the lungs of humanized PAP mice

Macrophages harbor great plasticity and adapt effectively to specific environmental factors. Here, we analyzed the adaptation of induced pluripotent stem cell (iPSC) derived macrophages to the lung environment. Human iPSC derived macrophages were transplanted intrapulmonary to humanized Pulmonary Alveolar Proteinosis (PAP) mice which display high pulmonary levels of surfactant and human GM-CSF. PAP is a life-threatening lung disease caused by GM-CSF receptor mutations and a differentiation block of alveolar macrophages (AM).Mice were transplanted four times in four consecutive weeks, and iPSC macrophages were re-isolated and analyzed two months after the first treatment.Pulmonary transplantation of iPSC macrophages led to pulmonary engraftment and in situ differentiation of iPSC macrophages which displayed the typical morphology of primary human AM and were red-Oil-O positive illustrating functional surfactant uptake. The surface marker profile of re-isolated macrophages was similar to that of primary human AM and was clearly distinct to that of iPSC macrophages before transplantation. The transcriptome of the iPSC macrophages after re-isolation had clearly changed compared to that of iPSC macrophages before transplantation and was most similar to that of hematopoietic stem cell derived AM like cells or primary human AM.Our data show that human iPSC derived macrophages can adapt to the lung environment in a humanized lung disease model. Future studies include the characteriza...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Paediatric Bronchology Source Type: research