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

Npj Regenerative Medicine
Li GuoThomas K Waddell

Abstract

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.

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Citations

May 24, 2019·Expert Review of Respiratory Medicine·Juan SnijderMary M Salvatore
Jul 9, 2020·American Journal of Respiratory Cell and Molecular Biology·Kamran AtabaiMichael J Podolsky
Jul 29, 2020·International Journal of Molecular Sciences·Pascal DuchesneauGolnaz Karoubi
Nov 20, 2020·European Respiratory Review : an Official Journal of the European Respiratory Society·Antoine FroidureArnaud Mailleux
Dec 2, 2021·Tissue Engineering. Part C, Methods·MohammadAli AhmadipourGolnaz Karoubi

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Methods Mentioned

BETA
PCR
lavage
fluorescence-activated cell sorting
chips

Clinical Trials Mentioned

NCT02013700
NCT02135380
NCT01919827
NCT01385644
NCT02277145

Software Mentioned

LightCycler 480
FlowJo
FlexiVent
FV10
- ASW
GraphPad Prism

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