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Published on: April 15, 2022
Engraftment of wild-type alveolar type II epithelial cells in surfactant protein C deficient mice
Camilla Predella1,2,3, Lauren Lapsley1, Keyue Ni1
1Division of Pediatric Critical Care Medicine and Hospital Medicine, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Insights
Cell therapy offers hope for children with surfactant deficiency lung disease. Transplanting healthy alveolar type II cells into a mouse model partially repaired lung damage and improved function.
Area of Science:
- Pulmonary Medicine
- Regenerative Medicine
- Genetics
Background:
- Childhood interstitial lung disease (chILD) from surfactant deficiency causes severe respiratory issues.
- Current treatments are limited, with lung transplantation facing organ shortages.
- Cell therapy using alveolar type II epithelial (ATII) cells is a potential therapeutic strategy.
Purpose of the Study:
- To test the efficacy of ATII cell transplantation in a mouse model of chILD.
- To provide proof-of-principle for using cell therapy to repair lungs affected by surfactant deficiency.
Main Methods:
- Utilized Sftpc knockout mice, a model for chILD-like disease.
- Administered low-dose bleomycin to condition the lungs for cell engraftment.
- Transplanted wild-type ATII cells into the conditioned mouse model.
Main Results:
- Engraftment of transplanted ATII cells was successful in the mouse model.
- Transplanted cells produced surfactant protein (SPC).
- Lung injury induced by bleomycin was attenuated for up to two months post-transplant.
Conclusions:
- Partial replacement of mutant ATII cells can promote lung repair in chILD-like disease.
- Cell therapy is a promising approach for treating childhood lung diseases caused by surfactant deficiency.
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.
