Abstract | RATIONALE: Although 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. OBJECTIVES: METHODS: Macrophages 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 RESULTS: On 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. CONCLUSIONS: We 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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Authors | Christine Happle, Nico Lachmann, Mania Ackermann, Anja Mirenska, Gudrun Göhring, Kathrin Thomay, Adele Mucci, Miriam Hetzel, Torsten Glomb, Takuji Suzuki, Claudia Chalk, Silke Glage, Oliver Dittrich-Breiholz, Bruce Trapnell, Thomas Moritz, Gesine Hansen |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 198
Issue 3
Pg. 350-360
(08 01 2018)
ISSN: 1535-4970 [Electronic] United States |
PMID | 29652170
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Topics |
- Animals
- Humans
- Induced Pluripotent Stem Cells
(metabolism, transplantation)
- Macrophages, Alveolar
(metabolism)
- Mice
- Polymerase Chain Reaction
- Pulmonary Alveolar Proteinosis
(metabolism, therapy)
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