title: Preconditioning allows engraftment of mouse and human embryonic lung cells, enabling lung repair in mice.
abstract: 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.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Chava
authors.initials: C
authors.lastname: Rosen
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Elias
authors.initials: E
authors.lastname: Shezen
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Aronovich
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yael Zlotnikov
authors.initials: YZ
authors.lastname: Klionsky
authors.affiliation: Pediatric Gastroenterology, Hadassah Mt. Scopus Medical Center, Hebrew University, Jerusalem, Israel.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Yaakov
authors.affiliation: Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Assayag
authors.affiliation: Department of Veterinary Resources, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Inbal Eti
authors.initials: IE
authors.lastname: Biton
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Orna
authors.initials: O
authors.lastname: Tal
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Guy
authors.initials: G
authors.lastname: Shakhar
authors.affiliation: 1] Department of Obstetric and Gynecology, Assaf Harofeh Medical Center, Zerifin, Israel. [2] Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Herzel
authors.initials: H
authors.lastname: Ben-Hur
authors.affiliation: 1] Department of Obstetric and Gynecology, Assaf Harofeh Medical Center, Zerifin, Israel. [2] Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Shneider
authors.affiliation: 1] Department of Obstetric and Gynecology, Assaf Harofeh Medical Center, Zerifin, Israel. [2] Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Vaknin
authors.affiliation: 1] Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. [2] Department of Obstetrics and Gynecology, Wolfson Medical Center, Tel Aviv, Israel.
authors.forename: Oscar
authors.initials: O
authors.lastname: Sadan
authors.affiliation: 1] Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. [2] Department of Anesthesiology, Wolfson Medical Center, Tel Aviv, Israel.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Evron
authors.affiliation: 1] Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. [2] Department of Pediatric Surgery, Schneider Children's Medical Center, Petach Tikvah, Israel.
authors.forename: Enrique
authors.initials: E
authors.lastname: Freud
authors.affiliation: Pediatric Pulmonology, Hadassah Mt. Scopus Medical Center Hebrew University, Jerusalem, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Shoseyov
authors.affiliation: Pediatric Gastroenterology, Hadassah Mt. Scopus Medical Center, Hebrew University, Jerusalem, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Wilschanski
authors.affiliation: Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Neville
authors.initials: N
authors.lastname: Berkman
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Hagin
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Carmit
authors.initials: C
authors.lastname: Hillel-Karniel
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Irit Milman
authors.initials: IM
authors.lastname: Krentsis
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Esther
authors.initials: E
authors.lastname: Bachar-Lustig
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Reisner
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000637:transplantation*; D005260:Female; D006801:Humans; D008168:Lung / Q000196:embryology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D012038:Regeneration; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014183:Transplantation, Heterologous
chemical_list: D001973:Bromodeoxyuridine