ArticleAmerican journal of respiratory and critical care medicine2018
Pulmonary Transplantation of Human Induced Pluripotent Stem Cell-derived Macrophages Ameliorates Pulmonary Alveolar Proteinosis.
Article in American journal of respiratory and critical care medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 73 citations in OpenAlex.
- Induced pluripotent stem cell-derived macrophages (iMacs) in translational medicine: Disease models, drug testing, and therapeutic applications.Molecular biology reports · 2026Review
- Modeling myeloid cell development in health and disease using induced pluripotent stem cells.Frontiers in immunology · 2026Review
- Immune activation and response dynamics of human iPSC-derived macrophages in tuberculosis infection models.Clinical & translational immunology · 2026Article
- CAR-macrophages in solid tumors: promise, progress, and prospects.NPJ precision oncology · 2025Review
- A stem cell-based platform for functional analysis of genetic variants in lung disease.bioRxiv : the preprint server for biology · 2025Article
- Induced pluripotent stem cell-derived macrophages as a platform for modelling human disease.Nature reviews. Immunology · 2025Review
- Immunoregulatory Macrophages Modify Local Pulmonary Immunity and Ameliorate Hypoxic Pulmonary Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Exploiting urine-derived induced pluripotent stem cells for advancing precision medicine in cell therapy, disease modeling, and drug testing.Journal of biomedical science · 2024Review
- Review
- Lung repair and regeneration: Advanced models and insights into human disease.Cell stem cell · 2024Review
- Macrophages derived from human induced pluripotent stem cells (iPSCs) serve as a high-fidelity cellular model for investigating HIV-1, dengue, and influenza viruses.Journal of virology · 2024Article
- Pulmonary Alveolar Proteinosis and new therapeutic concepts.Klinische Padiatrie · 2024Article
- Macrophage-based therapeutic approaches for cardiovascular diseases.Basic research in cardiology · 2024Review
- Adaptation of Human iPSC-Derived Macrophages Toward an Alveolar Macrophage-Like Phenotype Post-Intra-Pulmonary Transfer into Murine Models.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
- Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting.The Journal of clinical investigation · 2023Review
- 'Off the shelf' immunotherapies: Generation and application of pluripotent stem cell-derived immune cells.Cell proliferation · 2023Review
- Alveolar macrophages in pulmonary alveolar proteinosis: origin, function, and therapeutic strategies.Frontiers in immunology · 2023Review
- iPSC-Derived Macrophages: The Differentiation Protocol Affects Cell Immune Characteristics and Differentiation Trajectories.International journal of molecular sciences · 2022Article
- Forthcoming complications in recovered COVID-19 patients with COPD and asthma; possible therapeutic opportunities.Cell communication and signaling : CCS · 2022Review
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16 authors at 8 institutions in 8 countries.
Funding
Abstract
rationaleAlthough the transplantation of induced pluripotent stem cell (iPSC)-derived cells harbors enormous potential for the treatment of pulmonary diseases, in vivo data demonstrating clear therapeutic benefits of human iPSC-derived cells in lung disease models are missing.
objectivesWe have tested the therapeutic potential of iPSC-derived macrophages in a humanized disease model of hereditary pulmonary alveolar proteinosis (PAP). Hereditary PAP is caused by a genetic defect of the GM-CSF (granulocyte-macrophage colony-stimulating factor) receptor, which leads to disturbed macrophage differentiation and protein/surfactant degradation in the lungs, subsequently resulting in severe respiratory insufficiency.
methodsMacrophages derived from human iPSCs underwent intrapulmonary transplantation into humanized PAP mice, and engraftment, in vivo differentiation, and therapeutic efficacy of the transplanted cells were analyzed. MEASUREMENTS AND MAIN
resultsOn intratracheal application, iPSC-derived macrophages engrafted in the lungs of humanized PAP mice. After 2 months, transplanted cells displayed the typical morphology, surface markers, functionality, and transcription profile of primary human alveolar macrophages. Alveolar proteinosis was significantly reduced as demonstrated by diminished protein content and surfactant protein D levels, decreased turbidity of the BAL fluid, and reduced surfactant deposition in the lungs of transplanted mice.
conclusionsWe here demonstrate for the first time that pulmonary transplantation of human iPSC-derived macrophages leads to pulmonary engraftment, their in situ differentiation to an alveolar macrophage phenotype, and a reduction of alveolar proteinosis in a humanized PAP model. To our knowledge, this finding presents the first proof-of-concept for the therapeutic potential of human iPSC-derived cells in a pulmonary disease and may have profound implications beyond the rare disease of PAP.
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