RGD Reference Report - Therapeutic potential of hepatocyte-like-cells converted from stem cells from human exfoliated deciduous teeth in fulminant Wilson's disease. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Therapeutic potential of hepatocyte-like-cells converted from stem cells from human exfoliated deciduous teeth in fulminant Wilson's disease.

Authors: Fujiyoshi, Junko  Yamaza, Haruyoshi  Sonoda, Soichiro  Yuniartha, Ratih  Ihara, Kenji  Nonaka, Kazuaki  Taguchi, Tomoaki  Ohga, Shouichi  Yamaza, Takayoshi 
Citation: Fujiyoshi J, etal., Sci Rep. 2019 Feb 7;9(1):1535. doi: 10.1038/s41598-018-38275-y.
RGD ID: 25823141
Pubmed: PMID:30733544   (View Abstract at PubMed)
PMCID: PMC6367569   (View Article at PubMed Central)
DOI: DOI:10.1038/s41598-018-38275-y   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ATP7BHumanWilson disease  ISOAtp7b (Rattus norvegicus)compared to LEA/HokRGD 
Atp7bRatWilson disease  IAGP compared to LEA/HokRGD 
Atp7bMouseWilson disease  ISOAtp7b (Rattus norvegicus)compared to LEA/HokRGD 
Atp7bhtsRatWilson disease  IAGP compared to LEA/HokRGD 
LEC/HokRatWilson disease MODELIAGPcontrolled copper content dietcompared to LEA/HokRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Atp7bRatdecreased ceruloplasmin level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bhtsRatdecreased ceruloplasmin level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
LEC/HokRatdecreased ceruloplasmin level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bRatincreased circulating alanine transaminase level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bhtsRatincreased circulating alanine transaminase level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
LEC/HokRatincreased circulating alanine transaminase level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bRatincreased circulating aspartate transaminase level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bhtsRatincreased circulating aspartate transaminase level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
LEC/HokRatincreased circulating aspartate transaminase level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bRatincreased circulating bilirubin level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bhtsRatincreased circulating bilirubin level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
LEC/HokRatincreased circulating bilirubin level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bRatincreased liver copper level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bhtsRatincreased liver copper level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
LEC/HokRatincreased liver copper level  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bRatjaundice  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bhtsRatjaundice  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
LEC/HokRatjaundice  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bRatoxidative stress  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bhtsRatoxidative stress  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
LEC/HokRatoxidative stress  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bRatpremature death  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bhtsRatpremature death  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
LEC/HokRatpremature death  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bRatweight loss  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Atp7bhtsRatweight loss  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
LEC/HokRatweight loss  IAGPcontrolled copper content dietcompared to LEA/HokRGD 
Objects Annotated

Genes (Rattus norvegicus)
Atp7b  (ATPase copper transporting beta)
Atp7bhts  (ATPase copper transporting beta; hepatitis)

Genes (Mus musculus)
Atp7b  (ATPase, Cu++ transporting, beta polypeptide)

Genes (Homo sapiens)
ATP7B  (ATPase copper transporting beta)

Strains
LEC/Hok  (Long Evans Cinnamon)


Additional Information