Pulmonary Macrophage Transplantation Therapy
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Author
Suzuki, Takuji
Arumugam, Paritha
Sakagami, Takuro
Lachmann, Nico
Chalk, Claudia
Sallese, Anthony
Abe, Shuichi
Trapnell, Cole
Carey, Brenna
Moritz, Thomas
Malik, Punam
Lutzko, Carolyn
Wood, Robert E.
Trapnell, Bruce C.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/nature13807Metadata
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Suzuki, T., P. Arumugam, T. Sakagami, N. Lachmann, C. Chalk, A. Sallese, S. Abe, et al. 2014. “Pulmonary Macrophage Transplantation Therapy.” Nature 514 (7523): 450-454. doi:10.1038/nature13807. http://dx.doi.org/10.1038/nature13807.Abstract
SUMMARY Bone marrow transplantation is an effective cell therapy but requires myeloablation, which increases infection-risk and mortality. Recent lineage-tracing studies documenting that resident macrophage populations self-maintain independent of hematologic progenitors prompted us to consider organ-targeted, cell-specific therapy. Here, using GM-CSF receptor-β deficient (Csf2rb−/−) mice that develop a myeloid cell disorder identical to hereditary pulmonary alveolar proteinosis (hPAP) in children with CSF2RA/CSF2RB mutations, we show that pulmonary macrophage transplantation (PMT) of either wild-type or Csf2rb-gene-corrected macrophages without myeloablation was safe, well-tolerated, and that one administration corrected the lung disease, secondary systemic manifestations, normalized disease-related biomarkers, and prevented disease-specific mortality. PMT-derived alveolar macrophages persisted for at least one year as did therapeutic effects. Results identify mechanisms regulating alveolar macrophage population size in health and disease, indicate that GM-CSF is required for phenotypic determination of alveolar macrophages, and support translation of PMT as the first specific therapy for children with hPAP.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236859/pdf/Terms of Use
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