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Engraftment of wild-type alveolar type II epithelial cells in surfactant protein C deficient mice

Iezza, D.; Predella, C.; NI, K.; Murray, J. W.; Liu, H.-Y.; Saqi, A.; Glasser, S. W.; Dorrello, N. V.

2023-01-12 cell biology
10.1101/2023.01.12.523571 bioRxiv
Show 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 cellular 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 four months post-transplant. This study demonstrates that partial replacement of mutant ATII cells can promote lung repair in a mouse model of chILD.

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