RRC ID 81811
Author Fujiyoshi J, Yamaza H, Sonoda S, Yuniartha R, Ihara K, Nonaka K, Taguchi T, Ohga S, Yamaza T.
Title Therapeutic potential of hepatocyte-like-cells converted from stem cells from human exfoliated deciduous teeth in fulminant Wilson's disease.
Journal Sci Rep
Abstract Wilson's disease (WD) is an inherited metabolic disease arising from ATPase copper transporting beta gene (ATP7B) mutation. Orthotoropic liver transplantation is the only radical treatment of fulminant WD, although appropriate donors are lacking at the onset of emergency. Given the hepatogenic capacity and tissue-integration/reconstruction ability in the liver of stem cells from human exfoliated deciduous teeth (SHED), SHED have been proposed as a source for curing liver diseases. We hypothesized the therapeutic potential of SHED and SHED-converted hepatocyte-like- cells (SHED-Heps) for fulminant WD. SHED and SHED-Heps were transplanted into WD model Atp7b-mutated Long-Evans Cinnamon (LEC) rats received copper overloading to induce a lethal fulminant liver failure. Due to the superior copper tolerance via ATP7B, SHED-Hep transplantation gave more prolonged life-span of fulminant LEC rats than SHED transplantation. The integrated ATP7B-expressing SHED-Heps showed more therapeutic effects on to restoring the hepatic dysfunction and tissue damages in the recipient liver than the integrated naïve SHED without ATP7B expression. Moreover, SHED-Heps could reduce copper-induced oxidative stress via ATP7B- independent stanniocalcin 1 secretion in the fulminant LEC rats, suggesting a possible role for paracrine effect of the integrated SHED-Heps. Taken together, SHED-Heps offer a potential of functional restoring, bridging, and preventive approaches for treating fulminant WD.
Volume 9(1)
Pages 1535
Published 2019-2-7
DOI 10.1038/s41598-018-38275-y
PII 10.1038/s41598-018-38275-y
PMID 30733544
PMC PMC6367569
MeSH Animals Cell Differentiation Copper / toxicity Copper-Transporting ATPases / antagonists & inhibitors Copper-Transporting ATPases / genetics Copper-Transporting ATPases / metabolism Disease Models, Animal Glycoproteins / metabolism Hepatocytes / cytology Hepatocytes / metabolism Hepatocytes / transplantation* Hepatolenticular Degeneration / mortality Hepatolenticular Degeneration / pathology Hepatolenticular Degeneration / therapy* Humans Intercellular Signaling Peptides and Proteins / pharmacology Oxidative Stress / drug effects Paracrine Communication RNA Interference RNA, Small Interfering / metabolism Rats Rats, Inbred LEC Stem Cells / cytology* Stem Cells / metabolism Survival Rate Tooth, Deciduous / cytology*
IF 3.998
Resource
Human and Animal Cells Hep G2(RCB1886)