Abstract
BackgroundRecent studies have demonstrated that normal bone marrow (BM) cells transplantation can correct liver injury in a mouse model of Wilson disease (WD). However, it still remains unknown when BM cells transplantation should be administered. The aim of this study was to investigate the potential impact of normal BM cells transplantation at different stages of WD to correct liver injury in toxic milk (tx) mice.MethodsRecipient tx mice were sublethally irradiated (5 Gy) prior to transplantation. The congenic wild-type (DL) BM cells labeled with CM-DiI were transplanted via caudal vein injection into tx mice at the early (2 months of age) or late stage (5 months of age) of WD. The same volume of saline or tx BM cells were injected as controls. The DL donor cell population, copper concentration, serum ceruloplasmin oxidase activity and aspartate aminotransferase (AST) levels in the various groups were evaluated at 1, 4, 8 and 12 weeks post-transplant, respectively.ResultsThe DL BM cells population was observed from 1 to 12 weeks and peaked by the 4th week in the recipient liver after transplantation. DL BM cells transplantation during the early stage significantly corrected copper accumulation, AST across the observed time points and serum ceruloplasmin oxidase activity through 8 to 12 weeks in tx mice compared with those treated with saline or tx BM cells (all P < 0.05). In contrast, BM cells transplantation during the late stage only corrected AST levels from 4 to 12 weeks post-transplant and copper accumulation at 12 weeks post-transplant (all P < 0.05). No significant difference was found between the saline and tx BM cells transplantation groups across the observed time points (P > 0.05).ConclusionsEarly stage transplantation of normal BM cells is better than late stage transplantation in correcting liver function and copper metabolism in a mouse model of WD.
Highlights
Recent studies have demonstrated that normal bone marrow (BM) cells transplantation can correct liver injury in a mouse model of Wilson disease (WD)
BM cells transplanted into tx mice have been shown to engraft in the liver and produce partial metabolic disease correction via reducing liver copper and increasing ceruloplasmin oxidase activity, this effect may not be sustained over a 9-month period post-transplant [14]
Tx mice were allocated to one of the six groups as follows: 2-month-old mice treated with DL BM cells transplantation, 5-month-old mice treated with DL BM cells transplantation, 2- or 5-month-old mice treated with saline as a blank control and 2- or 5month-old mice treated with tx BM cells as a transplantation control (40 mice per group, female:male = 3:2)
Summary
Recent studies have demonstrated that normal bone marrow (BM) cells transplantation can correct liver injury in a mouse model of Wilson disease (WD). It still remains unknown when BM cells transplantation should be administered. BM cells transplanted into tx mice have been shown to engraft in the liver and produce partial metabolic disease correction via reducing liver copper and increasing ceruloplasmin oxidase activity, this effect may not be sustained over a 9-month period post-transplant [14].
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