Search: onr:"swepub:oai:lup.lub.lu.se:282c4a21-2944-49cc-b147-0761344fab3a" >
Modeling fibrotic a...
Modeling fibrotic alveolar transitional cells with pluripotent stem cell-derived alveolar organoids
-
- Ptasinski, Victoria (author)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Lungbioengineering och regeneration,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Lung Bioengineering and Regeneration,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas,AstraZeneca, Sweden
-
- Monkley, Susan J. (author)
- AstraZeneca, Sweden
-
- Öst, Karolina (author)
- AstraZeneca, Sweden
-
show more...
-
- Tammia, Markus (author)
- AstraZeneca, Sweden
-
- Alsafadi, Hani N. (author)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Lungbioengineering och regeneration,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Lung Bioengineering and Regeneration,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas
-
- Overed-Sayer, Catherine (author)
- AstraZeneca, UK
-
- Hazon, Petra (author)
- AstraZeneca, Sweden
-
- Wagner, Darcy E. (author)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Lungbioengineering och regeneration,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LTH profilområde: Teknik för hälsa,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Lung Bioengineering and Regeneration,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LTH Profile Area: Engineering Health,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas
-
- Murray, Lynne A. (author)
- AstraZeneca, UK
-
show less...
-
(creator_code:org_t)
- 2023
- 2023
- English.
-
In: Life Science Alliance. - 2575-1077. ; 6:8
- Related links:
-
http://dx.doi.org/10... (free)
-
show more...
-
https://lup.lub.lu.s...
-
https://doi.org/10.2...
-
show less...
Abstract
Subject headings
Close
- Repeated injury of the lung epithelium is proposed to be the main driver of idiopathic pulmonary fibrosis (IPF). However, available therapies do not specifically target the epithelium and human models of fibrotic epithelial damage with suitability for drug discovery are lacking. We developed a model of the aberrant epithelial reprogramming observed in IPF using alveolar organoids derived from human-induced pluripotent stem cells stimulated with a cocktail of pro-fibrotic and inflammatory cytokines. Deconvolution of RNA-seq data of alveolar organoids indicated that the fibrosis cocktail rapidly increased the proportion of transitional cell types including the KRT5-/KRT17+ aberrant basaloid phenotype recently identified in the lungs of IPF patients. We found that epithelial reprogramming and extracellular matrix (ECM) production persisted after removal of the fibrosis cocktail. We evaluated the effect of the two clinically approved compounds for IPF, nintedanib and pirfenidone, and found that they reduced the expression of ECM and pro-fibrotic mediators but did not completely reverse epithelial reprogramming. Thus, our system recapitulates key aspects of IPF and is a promising system for drug discovery.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database