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

Irit Milman Krentsis, Chava Rosen, Elias Shezen, Anna Aronovich, Bar Nathanson, Esther Bachar-Lustig, Neville Berkman, Miri Assayag, Guy Shakhar, Tali Feferman, Ran Orgad, Yair Reisner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)68-77
Number of pages10
JournalStem cells translational medicine
Volume7
Issue number1
DOIs
StatePublished - Jan 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press

Keywords

  • Adult
  • Lung
  • Progenitors
  • Transplantation

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