The secretome of induced pluripotent stem cells reduces lung fibrosis in part by hepatocyte growth factor.

Gazdhar, Amiq Ur Rahman; Grad, I; Tamò, Luca; Gugger, Mathias; Feki, Anis; Geiser, Thomas (2014). The secretome of induced pluripotent stem cells reduces lung fibrosis in part by hepatocyte growth factor. Stem cell research & therapy, 5(6), p. 123. BioMed Central 10.1186/scrt513

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INTRODUCTION Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrotic lung disease, resulting in respiratory insufficiency and reduced survival. Pulmonary fibrosis is a result of repeated alveolar epithelial microinjuries, followed by abnormal regeneration and repair processes in the lung. Recently, stem cells and their secretome have been investigated as a novel therapeutic approach in pulmonary fibrosis. We evaluated the potential of induced pluripotent stem cells (iPSC) conditioned media (iPSC-cm) to regenerate and repair the alveolar epithelium in vitro and improve bleomycin induced lung injury in vivo. METHODS IPSC-cm was collected from cultured iPSC derived from human foreskin fibroblasts and its biological effects on alveolar epithelial wound repair was studied in an alveolar wound healing assay in vitro. Furthermore, iPSC-cm was intratracheally instilled 7 days after bleomycin induced injury in the rat lungs and histologically and biochemically assessed 7 days after instillation. RESULTS iPSC-cm increased alveolar epithelial wound repair in vitro compared with medium control. Intratracheal instillation of iPSC-cm in bleomycin-injured lungs reduced the collagen content and improved lung fibrosis in the rat lung in vivo. Profibrotic TGFbeta1 and alpha-smooth muscle actin (alpha-sma) expression were markedly reduced in the iPSC-cm treated group compared with control. Antifibrotic hepatocyte growth factor (HGF) was detected in iPSC-cm in biologically relevant levels, and specific inhibition of HGF in iPSC-cm attenuated the antifibrotic effect of iPSC-cm, indicating a central role of HGF in iPSC-cm. CONCLUSION iPSC-cm increased alveolar epithelial wound repair in vitro and attenuated bleomycin induced fibrosis in vivo, partially due to the presence of HGF and may represent a promising novel, cell free therapeutic option against lung injury and fibrosis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Gazdhar, Amiq Ur Rahman; Tamò, Luca and Geiser, Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1757-6512

Publisher:

BioMed Central

Language:

English

Submitter:

Rahel Holderegger

Date Deposited:

10 Mar 2015 09:37

Last Modified:

26 Jun 2016 01:59

Publisher DOI:

10.1186/scrt513

PubMed ID:

25384638

BORIS DOI:

10.7892/boris.64350

URI:

https://boris.unibe.ch/id/eprint/64350

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