Induced pluripotent stem cell-derived lung alveolar epithelial type II cells reduce damage in bleomycin-induced lung fibrosis
Alvarez-Palomo, Belén (Banc de Sang i Teixits)
Sanchez-Lopez, Luis Ignacio (Institut d'Investigacions Biomèdiques de Barcelona)
Moodley, Yuben (University of Western Australia)
Edel, Michael J (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Serrano-Mollar, Anna (Institut d'Investigacions Biomèdiques de Barcelona)

Data:	2020
Resum:	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. 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 × 10 6 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. 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. 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.
Ajuts:	Ministerio de Ciencia e Innovación RYC-2010-06512 Ministerio de Ciencia e Innovación BFU2011-26596 Ministerio de Economía y Competitividad BFU2014-54467-P
Nota:	Altres ajuts: Fundació La Marató de TV3 (FBG309768)
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Induced pluripotent stem cells ; Alveolar type II cells ; Cell differentiation ; Idiopathic pulmonary fibrosis ; Cell therapy
Publicat a:	Stem cell research & therapy, Vol. 11 (june 2020) , ISSN 1757-6512

DOI: 10.1186/s13287-020-01726-3
PMID: 32493487

12 p, 6.7 MB

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