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Res Sq
ResearchSquare
Research Square
2693-5015
American Journal Experts

10.21203/rs.3.rs-4673915/v1
10.21203/rs.3.rs-4673915
preprint
1
Article
Engraftment of wild-type alveolar type II epithelial cells in surfactant protein C deficient mice
Dorrello Nicolino Valerio https://orcid.org/0000-0002-1801-4975

Predella Camilla https://orcid.org/0000-0003-3699-0256

Lapsley Lauren
Ni Keyue
Murray John
Liu Hsiao-Yun
Motelow Joshua
Snoeck Hans-Willem
Glasser Stephan
Saqi Anjali
13 9 2024
rs.3.rs-4673915https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
https://www.researchsquare.com/article/rs-4673915/v1
nihpp-rs4673915v1.pdf
Abstract

Childhood interstitial lung disease (chILD) secondary to pulmonary surfactant deficiency is a devastating chronic lung disease in children. Clinical presentation includes mild to severe respiratory failure and fibrosis. There is no specific treatment, except lung transplantation, which is hampered by a severe shortage of donor organs, especially for young patients. Repair of lungs with chILD represents a longstanding therapeutic challenge but cell therapy is a promising strategy. As surfactant is produced by alveolar type II epithelial (ATII) cells, engraftment with normal or gene-corrected ATII cells might provide an avenue to cure. Here we used a chILD disease-like model, Sftpc-/- mice, to provide proof-of-principle for this approach. Sftpc-/- mice developed chronic interstitial lung disease with age and were hypersensitive to bleomycin. We could engraft wild-type ATII cells after low dose bleomycin conditioning. Transplanted ATII cells produced mature SPC and attenuated bleomycin-induced lung injury up to two months post-transplant. This study demonstrates that partial replacement of mutant ATII cells can promote lung repair in a mouse model of chILD-like disease.
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