The role of HO-1/BMMSCs in rat reduced-size liver transplantation

Abstract

Objective To explore the effect and mechanism of heme oxygenase-1 (HO-1) gene modified bone marrow mesenchymal stem cells (BMMSCs) on rat reduced-size liver transplantation. Methods 50 male Brown Norway (BN) rats were used to prepare BMMSCs. Male Lewis and BN rats were 75, respectively. BN rats were randomly divided into model group (n=25), stem cell group (n=25) and combined group (n=25). Acute rejection models following 50% reduced-size transplantaton were established in rats using two-cuff technique, 1 ml of normal saline, BMMSCs suspension, or HO-1/BMMSCs suspension were injected immediately after surgery. Rats were executed at an instant, 3rd, 7th and 14th day after surgery to identify BMMSCs and HO-1/adenovirus infection efficiency. Evaluated hepatic pathology by HE staining. Liver function indexes were detected. Portal vein pressure on 7th day after surgery was detected. The levels of endothelin-1 (ET-1) and nitric oxide (NO) in serum were detected using ELISA. The expressions of ET-1 in liver were detected by immunohistochemistry staining and Western blotting. Results High purity BMMSCs were obtained and HO-1/BMMSCs were successfully infected. Compared with model group, liver tissue injury and rejection were alleviated in stem cell group and combined group, liver function was improved, and the combined group was superior to stem cell group. The portal vein pressure in model group, stem cell group, and combined group were 21.3±0.2 mmHg, 11.2±0.2 mmHg, and 10.1±0.1 mmHg, respectively. The portal vein pressure in three groups showed a decreasing trend, difference was statistically significant (P<0.05). On the 3rd, 7th and 14th day after surgery, compared with model group, the expression levels of ET-1 and NO in the stem cell group and the combined group were decreased, and the combined group was significantly lower than stem cell group (P<0.05). Conclusion HO-1/BMMSCs improved liver function and portal vein pressure after reduced-size liver transplantation in rats, and may play a protective role by regulating ET-1/NO expression. Key words: Heme oxygenase-1; Mesenchymal stromal cells; Liver transplantation; Rat; Portal pressure