Send to

Choose Destination
PLoS One. 2014 Nov 6;9(11):e111425. doi: 10.1371/journal.pone.0111425. eCollection 2014.

Transplantation of ATP7B-transduced bone marrow mesenchymal stem cells decreases copper overload in rats.

Author information

Department of Hepatobiliary Surgery Ward of General Surgery, The Affiliated Wuhu No. 2 People's Hospital of Wannan Medical College, Wuhu, Anhui Province, China.
Department of Hepatobiliary Surgery, Dongying People's Hospital, Dongying, Shandong Province, China.
Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province, China.



Recent studies have demonstrated that transplantation of ATP7B-transduced hepatocytes ameliorates disease progression in LEC (Long-Evans Cinnamon) rats, a model of Wilson's disease (WD). However, the inability of transplanted cells to proliferate in a normal liver hampers long-term treatment. In the current study, we investigated whether transplantation of ATP7B-transduced bone marrow mesenchymal stem cells (BM-MSCs) could decrease copper overload in LEC rats.


The livers of LEC rats were preconditioned with radiation (RT) and/or ischemia-reperfusion (IRP) before portal vein infusion of ATP7B-transduced MSCs (MSCsATP7B). The volumes of MSCsATP7B or saline injected as controls were identical. The expression of ATP7B was analyzed by real-time quantitative polymerase chain reaction (RT-PCR) at 4, 12 and 24 weeks post-transplantation. MSCATP7B repopulation, liver copper concentrations, serum ceruloplasmin levels, and alanine transaminase (ALT) and aspartate transaminase (AST) levels were also analyzed at each time-point post-transplantation.


IRP-plus-RT preconditioning was the most effective strategy for enhancing the engraftment and repopulation of transplanted MSCsATP7B. This strategy resulted in higher ATP7B expression and serum ceruloplasmin, and lower copper concentration in this doubly preconditioned group compared with the saline control group, the IRP group, and the RT group at all three time-points post-transplantation (p<0.05 for all). Moreover, 24 weeks post-transplantation, the levels of ALT and AST in the IRP group, the RT group, and the IRP-plus-RT group were all significantly decreased compared to those of the saline group (p<0.05 compared with the IRP group and RT group, p<0.01 compared with IRP-plus-RT group); ALT and AST levels were significantly lower in the IRP-plus-RT group compared to either the IRP group or the RT group (p<0.01 and p<0.05. respectively).


These results demonstrate that transplantation of MSCsATP7B into IRP-plus-RT preconditioned LEC rats decreased copper overload and was associated with an increase in MSC engraftment and repopulation.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center