[Flk1+ mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice].

ABSTRACT

Fibrosis is the common end stage of most liver diseases. Unfortunately, there is no effective treatment available currently. This study was designed to evaluate the effect of Flk1+ mesenchymal stem cells (MSC) from murine bone marrow (Flk1 + MSC) on fibrosis formation induced by carbon tetrachloride (CCl4). In this study Flk1+ MSC were isolated from bone marrow of male BALB/c mice. A CCl4 induced hepatic fibrosis model was used. Flk1+ MSC were systemically infused immediately or one week after the female mice were challenged with CCl4. Fibrosis index and donor cell engraftment were assessed two or five weeks after CCl4 challenge. We found that Flk1+ MSC transplantation immediately, but not one week after exposure to CCl4, significantly reduced CCl4-induced liver damage and collagen deposition. In addition, levels of hepatic hydroxyproline and serum fibrosis markers (HA, P-III-P) in mice receiving immediate Flk1+ MSC transplantation after CCl4 challenge were significantly lower compared to those of control mice. More importantly, histological examination suggested that hepatic damage recovery was much better in these immediately Flk1+ MSC-treated mice. Immunofluorescence, PCR, and fluorescence in situ hybridization (FISH) analysis revealed that donor cells engrafted into host liver, had epithelium-like morphology and expressed albumin (ALB), although at low frequency. In conclusion Flk1+ MSC might initiate endogenous hepatic tissue regeneration, engraft into host liver in response to CCl4 injury, and ameliorate its fibrogenic effects.