Congenital Pulmonary Alveolar Proteinosis iPS-derived hematopoietic progenitor cells (HPCs) reveal functional defects upon GM-CSF administration

Hereditary Pulmonary Alveolar Proteinosis (herPAP), caused by a mutation in the GM-CSF receptor β-chain (Csf2rb), is an extremely rare lung disease resulting from the inability of alveolar macrophages to clear the alveolar spaces from surfactant phospholipids. Since current treatment options are extremely limited, we here investigate the suitability of a gene therapy approach based on hematopoietic cells derived from induced pluripotent stem cells (iPSC). Studies were performed in a murine model for Csf2rb-deficiency (Csf2rb-/-). Therefore iPSCs were generated from lin- bone marrow cells of Csf2rb-/- mice utiliz…