Preconditioning allows engraftment of mouse and human embryonic lung cells, enabling lung repair in mice
| Autor: | Miri Assayag, Shmuel Evron, David Hagin, Willem E. Fibbe, Inbal E. Biton, Neville Berkman, Yasmin Yaakov, Oscar Sadan, Anna Aronovich, Zvi Vaknin, Chava Rosen, Orna Tal, Irit Milman Krentsis, Esther Bachar-Lustig, Michael Wilschanski, Guy Shakhar, Carmit Hillel-Karniel, David Shneider, Elias Shezen, Enrique Freud, David Shoseyov, Herzel Ben-Hur, Yael Zlotnikov Klionsky, Yair Reisner |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Pathology medicine.medical_specialty Transplantation Conditioning Transplantation Heterologous Mice SCID Pulmonary compliance Biology General Biochemistry Genetics and Molecular Biology Mice medicine Animals Humans Regeneration Progenitor cell Lung Embryonic Stem Cells Mice Inbred C3H Transplantation Chimera Mesenchymal stem cell General Medicine respiratory system Embryonic stem cell respiratory tract diseases Transplantation Mice Inbred C57BL medicine.anatomical_structure Bromodeoxyuridine Female Bone marrow Stem cell |
| Zdroj: | Nature Medicine, 21(8), 869-879 |
| ISSN: | 1546-170X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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