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Title

Induced pluripotent stem cell-derived lung alveolar epithelial type II cells reduce damage in bleomycin-induced lung fibrosis

AuthorsAlvarez-Palomo, Belén; Sanchez-Lopez, Luis I; Moodley, Yuben; Edel, Michael J; Serrano-Mollar, Anna
KeywordsInduced pluripotent stem cells
Alveolar type II cells
Cell differentiation
Idiopathic pulmonary fibrosis
Cell therapy
Issue Date3-Jun-2020
PublisherBioMed Central
CitationStem Cell Research & Therapy. 2020 Jun 03;11(1):213
AbstractAbstract Background Idiopathic pulmonary fibrosis is a chronic, progressive, and severe disease with a limited response to currently available therapies. Epithelial cell injury and failure of appropriate healing or regeneration are central to the pathogenesis of idiopathic pulmonary fibrosis. The purpose of this study is to investigate whether intratracheal transplantation of alveolar type II-like cells differentiated from induced pluripotent stem cells can stop and reverse the fibrotic process in an experimental model of bleomycin-induced lung fibrosis in rats. Methods Human induced pluripotent stem cells were differentiated to alveolar type II-like cells and characterized. Lung fibrosis was induced in rats by a single intratracheal instillation of bleomycin. Animals were transplanted with human induced pluripotent stem cells differentiated to alveolar type II-like cells at a dose of 3 × 106 cells/animal 15 days after endotracheal bleomycin instillation when the animal lungs were already fibrotic. Animals were sacrificed 21 days after the induction of lung fibrosis. Lung fibrosis was assessed by hydroxiprolin content, histologic studies, and the expression of transforming growth factor-β and α-smooth muscle actin. Results Cell transplantation of alveolar type II-like cells differentiated from induced pluripotent stem cells can significantly reduce pulmonary fibrosis and improve lung alveolar structure, once fibrosis has already formed. This is associated with the inhibition of transforming growth factor-β and α-smooth muscle actin in the damaged rat lung tissue. Conclusion To our knowledge, this is the first data to demonstrate that at the fibrotic stage of the disease, intratracheal transplantation of human induced pluripotent differentiated to alveolar type II-like cells halts and reverses fibrosis.
URIhttps://doi.org/10.1186/s13287-020-01726-3
http://hdl.handle.net/10261/213624
Appears in Collections:Colección Biomed Central-Chemistry Central-Springer Open
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