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ID 119341
Title Alternative
Dental Pulp Stem Cell Factors for Treating LF
Author
Hirata, Marina Nagoya University
Ishigami, Masatoshi Nagoya University
Matsushita, Yoshihiro Nagoya University
Ito, Takanori Nagoya University
Hattori, Hisashi Nagoya University
Hibi, Hideharu Nagoya University
Goto, Hidemi Nagoya University
Ueda, Minoru Nagoya University
Keywords
Liver fibrosis
Dental pulp stem cells
Conditioned media
Inflammation
Macrophages
Content Type
Journal Article
Description
Chronic liver injury from various causes often results in liver fibrosis (LF). Although the liver possesses endogenous tissue-repairing activities, these can be overcome by sustained inflammation and excessive fibrotic scar formation. Advanced LF leads to irreversible cirrhosis and subsequent liver failure and/or hepatic cancer. Here, using the mouse carbon tetrachloride (CCl4)-induced LF model, we showed that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED-derived serum-free conditioned medium (SHED-CM) resulted in fibrotic scar resolution. SHED-CM suppressed the gene expression of proinflammatory mediators, such as TNF-α, IL-1β, and iNOS, and eliminated activated hepatic stellate cells by inducing their apoptosis, but protected parenchymal hepatocytes from undergoing apoptosis. In addition, SHED-CM induced tissue-repairing macrophages that expressed high levels of the profibrinolytic factor, matrix metalloproteinase 13. Furthermore, SHED-CM suppressed the CCl4-induced apoptosis of primary cultured hepatocytes. SHED-CM contained a high level of hepatocyte growth factor (HGF). Notably, HGF-depleted SHED-CM (dHGF-CM) did not suppress the proinflammatory response or resolve fibrotic scarring. Furthermore, SHED-CM, but not dHGF-CM, inhibited CCl4-induced hepatocyte apoptosis. These results suggest that HGF plays a central role in the SHED-CM-mediated resolution of LF. Taken together, our findings suggest that SHED-CM provides multifaceted therapeutic benefits for the treatment of LF.
Journal Title
STEM CELLS Translational Medicine
ISSN
21576580
21576564
NCID
AA12597700
Publisher
AlphaMed Press|Oxford University Press
Volume
5
Issue
10
Start Page
1416
End Page
1424
Published Date
2016-06-08
Rights
STEM CELLS Translational Medicine® is a monthly, peer-reviewed, online only, open access journal.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Oral Sciences