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Pulmonary macrophage transplantation therapy
Open accessAbstract
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 independently of haematological progenitors prompted us to consider organ-targeted, cell-specific therapy. Here, using granulocyte–macrophage colony-stimulating factor (GM-CSF) receptor-β-deficient (Csf2rb−/−) mice that develop a myeloid cell disorder identical to hereditary pulmonary alveolar proteinosis (hPAP) in children with CSF2RA or CSF2RB mutations, we show that pulmonary macrophage transplantation (PMT) of either wild-type or Csf2rb-gene-corrected macrophages without myeloablation was safe and well-tolerated and that one administration corrected the lung disease, secondary systemic manifestations and normalized disease-related biomarkers, and prevented disease-specific mortality. PMT-derived alveolar macrophages persisted for at least one year as did therapeutic effects. Our findings 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.
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Metadata
- Authors
- Suzuki, T., Arumugam, P., Sakagami, T., Lachmann, N., Chalk, C., Sallese, A., Abe, S., Trapnell, C., Carey, B., Moritz, T., Malik, P., Lutzko, C., Wood, R. E., & Trapnell, B. C.
- Venue
- Nature
- Published
- 2014-10
- Volume
- 514
- Issue
- 7523
- Pages
- 450-454
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1997396254
- Cited by
- 307
- References
- 5
- FWCI
- 20.41
- Type
- journal article
- Language
- en
- Open access
- green
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