Kennelly, Helen and Mahon, Bernard P. and English, Karen
(2016)
Human mesenchymal stromal cells exert HGF dependent cytoprotective effects in a human relevant pre-clinical model of COPD.
Scientific Reports, 6 (38207).
ISSN 2045-2322
Abstract
Bone-marrow derived mesenchymal stromal cells (MSCs) have potent immunomodulatory and tissue
reparative properties, which may be beneficial in the treatment of inflammatory diseases such as
COPD. This study examined the mechanisms by which human MSCs protect against elastase induced
emphysema. Using a novel human relevant pre-clinical model of emphysema the efficacy of human
MSC therapy and optimal cell dose were investigated. Protective effects were examined in the lung
through histological examination. Further in vivo experiments examined the reparative abilities of
MSCs after tissue damage was established and the role played by soluble factors secreted by MSCs. The
mechanism of MSC action was determined in using shRNA gene knockdown. Human MSC therapy and
MSC conditioned media exerted significant cytoprotective effects when administered early at the onset
of the disease. These protective effects were due to significant anti-inflammatory, anti-fibrotic and antiapoptotic
mechanisms, mediated in part through MSC production of hepatocyte growth factor (HGF).
When MSC administration was delayed, significant protection of the lung architecture was observed
but this was less extensive. MSC cell therapy was more effective than MSC conditioned medium in this
emphysema model.
| Item Type: |
Article
|
| Keywords: |
Human mesenchymal stromal cells; HGF dependent cytoprotective; effects; human relevant pre-clinical model; COPD; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
10579 |
| Identification Number: |
https://doi.org/10.1038/srep38207 |
| Depositing User: |
Karen English
|
| Date Deposited: |
25 Feb 2019 12:02 |
| Journal or Publication Title: |
Scientific Reports |
| Publisher: |
Nature Publishing Group |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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