OBJECTIVE: Wilson’s disease (WD) is an inherited metabolic disease arising from ATP7B mutation. Lifelong treatment with chelating agents and/or zinc stabilizes the patient for clinical remission. However, fulminant liver failure is challenging to control because of an urgent need of liver transplantation. We previously reported a 15-year-old girl who developed acute hemolysis and liver failure as an initial manifestation of WD during primary human parvovirus B19 infection. Given the hepatogenic capacity and tissue-integration/reconstruction ability in the liver, mesenchymal stem/stromal cells (MSC) have been proposed as a source for curing liver diseases. Stem cells from human exfoliated deciduous teeth (SHED) are the MSC having highly proliferative and hepatogenic capacity. We hypothesized the therapeutic potential of SHED and SHED-converted hepatocyte-like-cells (SHED-Heps) to be an alternative source for rescuing fulminant WD. 
METHOD: We transplanted SHED-Heps and SHED into LEC rats with fulminant hepatitis under copper overloading and investigated the life-span of the fulminant LEC rats and the efficacy to the fulminant hepatitis and damaged tissue in the recipient liver.
RESULT: Due to the superior copper tolerance via ATP7B, SHED-Hep-transplantation gave more prolonged life-span of fulminant WD model in Atp7b-mutated Long-Evans Cinnamon (LEC) rats with copper overloading, and showed more effective in restoring the deficient function and tissue damages in the recipient liver than SHED. Moreover, SHED-Heps, as well as SHED, could reduce copper-induced oxidative stress via ATP7B-independent stanniocalcin 1 secretion in the fulminant LEC rats, suggesting a possible role for paracrine effect. 
CONCLUSION: SHED-Heps offer a potentially source of functional restoring, bridging, and preventive approaches for treating fulminant WD.