Objective       To determine the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) in the treatment of hepatotoxicity in hemophagocytic lymphohistocytosis (HLH)-like mouse model and investigate the possible mechanism. Methods      hUC-MSCs were stained with CM-Dil fluorescent carbocyanite in vitro. A total of 54 adult C57BL/6 mice were randomly assigned to the model injury group (PBS group)

stem cell transplantation group (MSC group) and normal control group (CON group). The HLH-like mouse model was induced by CPG oligodeoxynucleotide (CPG-ODN 1826) and interferon (IFN)-γ. Then the CM-Dil-labeled hUC-MSCs were transplanted into the mice of the MSC group via caudal vein. The general conditions were observed in all the mice in 1

3 and 7 d after transplantation. The blood samples in the above 3 time points were collected to measure the serum contents of aspartate transaminase (AST)

alanine transaminase (ALT)

albumin (ALB) and triglyceride (TG)

counts of platelets (PLT)

white blood cells (WBC) and red blood cells (RBC)

and level of hemoglobin (HGB). In 7 d after transplantation

liver weight was determined

the pathohistological changes were observed with hematoxylin-eosin staining

and the number of activated macrophages was tested by immunohistochemical assay. Fluorescent microscopy was used to observe the localization of labeled hUC-MSCs in the liver

and immunofluorescence assay was employed to count the cells positive to anti-human albumin antibody.      Results         When compared with the PBS group

the mice in the MSC group showed obviously better general condition

decreased ratio of liver weight to body weight (P0.05)

decreased contents of AST

ALT

and TG (P0.05)

no obvious change in the ALB content (P0.05)

and elevated counts of WBC

PLT

RBC and HGB (P0.05). There were less lymphocytes infiltration in the liver

  reduced activated macrophages (P0.05)

no expression of human ALB

and attenuated liver damage after hUC-MSCs transplantation. The CM-Dil labeled hUC-MSCs were found in the liver tissue of the MSC group after transplantation.   Conclusion       The CM-Dil labeled hUC-MSCs are implanted into the damaged liver tissue by caudal vein transplantation. The transplantation improves liver function

repairs injured liver tissue

and reduces activated macrophages

which are not through the MSCs-derived hepatocytelike cells.