Therapeutic effect of estradiol-pretreated human bone marrow mesenchymal stem cells on liver cirrhosis in mice

Objective To explore the effect of estradiol on human bone marrow mesenchymal stem cells( BMSCs) and the therapeutic effect of estradiol- pretreated BMSCs on liver cirrhosis in mice. Methods Third- passage BMSCs were divided into control( untreated with estradiol) and experimental groups( treated with different concentrations of estradiol); the effect of estradiol on the proliferative activity of BMSCs was measured by MTT assay. Apoptosis was induced by H2O2 in the control and experimental groups of BMSCs,with normal BMSCs as the blank group; the effect of estradiol on apoptosis in BMSCs was tested by trypan blue staining and quantitative real- time PCR of caspase- 3 mRNA. Forty- six normal male C57 BL mice were assigned to control,model,BMSC transplantation,and estradiol- pretreated BMSC transplantation groups. An animal model of liver cirrhosis was established by intraperitoneal injection of CCl4. At 12 weeks after CCl4 injection,estradiol- pretreated and untreated BMSCs were transplanted into mice through the tail vein. At 4 weeks after BMSC transplantation,blood samples were collected for serum alanine aminotransferase( ALT) and serum aspartate aminotransferase( AST) assays. The stage of liver fibrosis was determined by hematoxylin- eosin and Masson staining. Type I collagen( collagen I) expression was analyzed by RT- PCR. Normally distributed categorical data( with homogeneous variances) were analyzed using ANOVA,followed by pairwise comparisons using LSD test; non- normally distributed data( with heterogeneous variances) were analyzed using Mann- Whitney rank- sum test. Results All the experimental groups had higher proliferative activity than the control group( F = 730. 08,P = 0. 000). H2O2 promoted apoptosis in BMSCs,with lower apoptosis rate in the experimental groups than in the control group( F = 258. 34,P = 0. 000). Caspase- 3 mRNA expression was significantly different between the control and experimental groups( F = 50. 29,P = 0. 000). Additionally,there were significant differences in rats between the model,BMSC transplantation,and estradiol- pretreated BMSC transplantation groups in terms of ALT( P = 0. 000 for all),AST( P < 0. 05 for all),fiber ratio( P < 0. 05 for all),and collagen I mRNA expression( P < 0. 05 for all). Conclusion Estradiol promotes the proliferation and reduces H2O2- induced apoptosis in BMSCs. BMSCs can improve liver cirrhosis and their therapeutic effect is enhanced by estradiol pretreatment.