To investigate the protective effect of human umbilical cord mesenchymal stem cell (MSC) on liver transplant rats with moderate or severe donor fatty livers.

Lewis rats were given high fat diets to established models of moderate or severe fatty livers, and orthotopic liver transplantation (LT) was performed on rats using modified Kamada′s two-cuff technique. The donors were Lewis rats with moderate or severe fatty liver and the recipients were inbred strain Brown Norway rats. Thirty-two LT rats were randomly divided into two groups according to the random number table: MSC group (n=16) and control group (n=16). The rats in MSC group were injected with 1.5 ml normal saline containing 2×10⁶ MSCs through penile dorsal veins immediately after LT, while the rats in control group were only injected with 1.5 ml normal saline through penile dorsal veins. Four rats from each group were put to death respectively on day 1 and day 3 after operation, and the samples of serum and grafted liver tissues were collected. The levels of serum alanine aminotransferase (ALT), total bilirubin (TB) and the contents of malondialdehyde (MDA), tumor necrosis factor (TNF)- α in grafted liver tissues of two groups were observed. The damage of grafted liver tissues was observed through pathological examination. The postoperative survival of the other rats was also observed. Experimental data between two groups were compared by t test. Survival analysis and comparision of rats between two groups were performed by Kaplan-Meier method and Log-rank test.

The level of serum ALT on day 1 after operation was (501±42)U/L in MSC group, and was (619±73)U/L in control group, there was significant difference between them (t=-2.890, P<0.05). The level of serum ALT on day 3 after operation was (385±65)U/L in MSC group, and was (1190±118)U/L in control group, there was significant difference between them (t=-11.980, P<0.05). The level of TB on day 1 after operation was (31±8)μmol/L in MSC group, and was (32±6)μmol/L in control group, there was no significant difference between them (t=-2.410, P>0.05). The level of TB on day 3 after operation was (51±9)μmol/L in MSC group, and was (91±14)μmol/L in control group, there was significant difference between them (t=-4.807, P<0.05). The content of MDA in grafted liver tissues on day 1 after operation was (4.9±0.8)mmol/mg in MSC group, and was (7.4±0.8)mmol/mg in control group, there was significant difference between them (t=-4.415, P<0.05). The content of MDA in grafted liver tissues on day 3 after operation was (3.8±0.6)mmol/mg in MSC group, and was (7.9±0.9)mmol/mg in control group, there was significant difference between them (t=-7.597, P<0.05). The content of TNF-α in grafted liver tissues on day 1 after operation was (1.04±0.18)ng/L in MSC group, and was (1.61±0.21)ng/L in control group, there was significant difference between them (t=-4.203, P<0.05). The content of TNF-α in grafted liver tissues on day 3 after operation was (0.87±0.06)ng/L in MSC group, and was (1.92±0.22)ng/L in control group, there was significant difference between them (t=-9.561, P<0.05). On day 1, 3 after operation, a large number of leukocyte infiltration, disorder of hepatic lobule structure, hepatic sinusoid congestion were observed in grafted liver tissues of control group, while milder local response was observed in MSC group. The histologic changes in MSC group was evidently milder than that in control group. There were 6 rats (6/8) survived for over 1 week in MSC group while only 1 rat (1/8) in control group. There was significant difference in the cumulative survival rates after operation between rats of two groups (χ²=6.703, P<0.05).

Human umbilical cord MSC plays a role in the protection of liver transplant rats with moderate or severe donor fatty livers.