Hereditary pulmonary alveolar proteinosis (herPAP) is a rare life-threatening disease characterized by the slow accumulation of lipoproteins in the lungs. Surfactant and other lipoproteins are typically cleared from alveoli by a specialized group of cells called alveolar macrophages that require the signaling molecule termed granulocyte macrophage colony-stimulating growth factor (GM-CSF) to maintain normal surfactant levels. With herPAP, the GM-CSF receptor on the alveolar macrophages contains mutations that render it ineffective. Thus, as surfactant builds up, air is prevented from entering the alveoli and oxygen from passing into the blood, resulting in breathlessness and respiratory insufficiency.
A team of researchers from Hannover Medical School demonstrated that a single transplantation of murine macrophages derived from induced pluripotent stem cells (iPSC) into the lungs of mice suffering from herPAP can effectively treat this life-threatening disease.
The authors deployed iPSC-derived macrophages in an established murine herPAP disease model. The transplanted iPSC-derived macrophages successfully established residency in the airways, and no iPSC-derived cells were detected in other tested organs and tissues, indicating high organ-specificity of the engraftment. Once in the lungs, the iPSC-derived macrophages effectively adopted an alveolar macrophage transcriptional profile. Functionally, the transplanted cells were able to clear the surfactant from the alveoli and alleviate the disease phenotype in the mice. Furthermore, histology of other organs and tissues revealed no signs of inflammation or other adverse effects, underscoring the clinical feasibility of this therapeutic approach.
The article titled “iPSC-Derived Macrophages Effectively Treat Pulmonary Alveolar Proteinosis in Csf2rb-Deficient Mice” was published in Stem Cell Reports.