Preconditioning allows engraftment of mouse and human embryonic lung cells, enabling lung repair in mice.

Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE

Publication: New York Ny : Nature Publishing Company
Original Publication: New York, NY : Nature Pub. Co., [1995-

Transplantation Conditioning*; Embryonic Stem Cells/*transplantation ; Lung/*embryology; Animals ; Bromodeoxyuridine/metabolism ; Female ; Humans ; Male ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, SCID ; Regeneration ; Transplantation Chimera ; Transplantation, Heterologous

Repair of injured lungs represents a longstanding therapeutic challenge. We show that human and mouse embryonic lung tissue from the canalicular stage of development (20-22 weeks of gestation for humans, and embryonic day 15-16 (E15-E16) for mouse) are enriched with progenitors residing in distinct niches. On the basis of the marked analogy to progenitor niches in bone marrow (BM), we attempted strategies similar to BM transplantation, employing sublethal radiation to vacate lung progenitor niches and to reduce stem cell competition. Intravenous infusion of a single cell suspension of canalicular lung tissue from GFP-marked mice or human fetal donors into naphthalene-injured and irradiated syngeneic or SCID mice, respectively, induced marked long-term lung chimerism. Donor type structures or 'patches' contained epithelial, mesenchymal and endothelial cells. Transplantation of differentially labeled E16 mouse lung cells indicated that these patches were probably of clonal origin from the donor. Recipients of the single cell suspension transplant exhibited marked improvement in lung compliance and tissue damping reflecting the energy dissipation in the lung tissues. Our study provides proof of concept for lung reconstitution by canalicular-stage human lung cells after preconditioning of the pulmonary niche.

Comment in: Nat Med. 2015 Aug;21(8):842-4. (PMID: 26248265)

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G34N38R2N1 (Bromodeoxyuridine)

Date Created: 20150714 Date Completed: 20151104 Latest Revision: 20181113

20231215

10.1038/nm.3889

26168294