Mesenchymal stem cells from human umbilical cords ameliorate mouse hepatic injury in vivo

Abstract

Aims: To investigate human umbilical cord-derived mesenchymal stem cells (hUCMSCs) for use in the reversal of mouse hepatic injury.

Methods: Human umbilical cord-derived mesenchymal stem cells, characterized by flow cytometry, were transplanted into carbon tetrachloride (CCl(4))-injured mice, and then followed for determination of localization and differentiation. Reverse transcriptase-polymerase chain reaction for the human 17alpha gene and fluorescence in situ hybridization analysis for the human X chromosome were used to locate exogenous hUCMSCs in mouse livers. Peripheral blood and liver specimens were collected at 7, 14 and 21 days after transplantation. For evaluating the recovery of injured liver tissues, serum aminotransferase was measured, and the pathological state of the hepatocytes was assessed.

Results: The hUCMSCs were positive for the human MSC-specific markers CD13, CD29, CD44, CD105 and nerve growth factor receptor, but negative for the haematopoietic lineage markers CD31, CD34, CD38, CD45 and HLA-DR. Under conditions favouring differentiation in vivo, the expression of tryptophan 2,3-dioxygenase, human alpha-fetoprotein, cytokeratin 18, fibroblast secretory protein 1 and alpha-smooth-muscle-actin was detectable after hUCMSCs administration to mice subjected to liver injury. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labelling and proliferating cell nuclear antigen staining showed that transplanted hUCMSCs could inhibit hepatocyte apoptosis and facilitate proliferation. Serum aminotransferases were decreased after transplantation of hUCMSCs into the injured mice, and hepatocyte denaturation was reduced.

Conclusions: Human umbilical cord-derived mesenchymal stem cells can enhance recovery of CCl(4)-injured mouse liver, providing evidence that such therapy could be useful for liver disorders or injury.