Interrupted reprogramming of alveolar type II cells induces progenitor-like cells that ameliorate pulmonary fibrosis.

Autor:	Guo L; 1Division of Thoracic Surgery, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, ON Canada., Karoubi G; 1Division of Thoracic Surgery, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, ON Canada., Duchesneau P; 1Division of Thoracic Surgery, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, ON Canada., Aoki FG; 1Division of Thoracic Surgery, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, ON Canada., Shutova MV; Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, ON Canada., Rogers I; Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, ON Canada.; 3Department of Physiology, University of Toronto, Toronto, ON Canada.; 4Department of Obstetrics & Gynecology, University of Toronto, Toronto, ON Canada., Nagy A; Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, ON Canada.; 4Department of Obstetrics & Gynecology, University of Toronto, Toronto, ON Canada.; 5Institute of Medical Science, University of Toronto, Toronto, ON Canada.; 6Monash University, Melbourne, VIC Australia., Waddell TK; 1Division of Thoracic Surgery, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, ON Canada.; 5Institute of Medical Science, University of Toronto, Toronto, ON Canada.
Jazyk:	angličtina
Zdroj:	NPJ Regenerative medicine [NPJ Regen Med] 2018 Sep 04; Vol. 3, pp. 14. Date of Electronic Publication: 2018 Sep 04 (Print Publication: 2018).
DOI:	10.1038/s41536-018-0052-5
Abstrakt:	We describe here an interrupted reprogramming strategy to generate "induced progenitor-like (iPL) cells" from alveolar epithelial type II (AEC-II) cells. A carefully defined period of transient expression of reprogramming factors (Oct4, Sox2, Klf4, and c-Myc (OSKM)) is able to rescue the limited in vitro clonogenic capacity of AEC-II cells, potentially by activation of a bipotential progenitor-like state. Importantly, our results demonstrate that interrupted reprogramming results in controlled expansion of cell numbers yet preservation of the differentiation pathway to the alveolar epithelial lineage. When transplanted to the injured lungs, AEC-II-iPL cells are retained in the lung and ameliorate bleomycin-induced pulmonary fibrosis. Interrupted reprogramming can be used as an alternative approach to produce highly specified functional therapeutic cell populations and may lead to significant advances in regenerative medicine. Competing Interests: The authors declare no competing interests.
Databáze:	MEDLINE
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