Lung Injury Repair by Transplantation of Adult Lung Cells Following Preconditioning of Recipient Mice

• Published in: Stem cells translational medicine Vol. 7; no. 1; pp. 68 - 77
• Main Authors: Milman Krentsis, Irit, Rosen, Chava, Shezen, Elias, Aronovich, Anna, Nathanson, Bar, Bachar‐Lustig, Esther, Berkman, Neville, Assayag, Miri, Shakhar, Guy, Feferman, Tali, Orgad, Ran, Reisner, Yair
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.01.2018; John Wiley and Sons Inc
• Subjects: Adult; Analysis; Bone marrow; Bone marrow transplantation; Cell Delivery Strategies; Colonization; Developmental stages; Dimensional analysis; Embryogenesis; Epithelial cells; Ethylenediaminetetraacetic acid; Experiments; Females; Fetuses; Intravenous administration; Lineage Specific Differentiation; Lung; Lung Stem Cells; Lung transplantation; Lungs; Mesenchyme; Microscopy; Naphthalene; Progenitors; Proteins; Radiation; Regeneration; Respiratory diseases; Respiratory function; Rodents; Stem cell transplantation; Stem cells; Tissue‐specific Progenitor and Stem cells; Translational s and Reviews; Transplantation; Variance analysis; Adult; Transplantation; Progenitors; Lung
• ISSN: 2157-6564; 2157-6580; 2157-6580
• DOI: 10.1002/sctm.17-0149

Repair of injured lungs represents a longstanding therapeutic challenge. We recently demonstrated that human and mouse embryonic lung tissue from the canalicular stage of development are enriched with lung progenitors, and that a single cell suspension of canalicular lungs can be used for transplantation, provided that lung progenitor niches in the recipient mice are vacated by strategies similar to those used in bone marrow transplantation. Considering the ethical limitations associated with the use of fetal cells, we investigated here whether adult lungs could offer an alternative source of lung progenitors for transplantation. We show that intravenous infusion of a single cell suspension of adult mouse lungs from GFP+ donors, following conditioning of recipient mice with naphthalene and subsequent sublethal irradiation, led to marked colonization of the recipient lungs, at 6–8 weeks post‐transplant, with donor derived structures including epithelial, endothelial, and mesenchymal cells. Epithelial cells within these donor‐derived colonies expressed markers of functionally distinct lung cell types, and lung function, which is significantly compromised in mice treated with naphthalene and radiation, was found to be corrected following transplantation. Dose response analysis suggests that the frequency of patch forming cells in adult lungs was about threefold lower compared to that found in E16 fetal lungs. However, as adult lungs are much larger, the total number of patch forming cells that can be collected from this source is significantly greater. Our study provides proof of concept for lung regeneration by adult lung cells after preconditioning to vacate the pulmonary niche. Stem Cells Translational Medicine 2018;7:68–77 The intravenous infusion of a single cell suspension of adult mouse lungs from GFP+ donors following conditioning of recipient mice with naphthalene and subsequent sublethal irradiation, leads to marked colonization of the recipient lungs, at 6–8 weeks post‐transplant, with donor derived structures including epithelial, endothelial, and mesenchymal cells as well as to lung functional repair.