[Immune intervention of human umbilical cord mesenchymal stem cells on sepsis rats].

OBJECTIVE: To investigate the effect of human umbilical cord mesenchymal stem cells (UC-MSCs) on immune cells and inflammatory factors in septic rats.

METHODS: 184 male Sprague-Dawley (SD) rats were divided into normal control group (n = 8), sham operation group (n = 48), sepsis model group (n = 64), and UC-MSCs treatment group (n = 64). An animal model of sepsis was produced by cecal ligation and puncture (CLP). In the UC-MSCs treatment group 1 mL UC-MSCs (2×10(6)/mL) were injected intraperitoneally at 1 hour after the model establishment; the sham operation group and the sepsis model group were given the same amount of saline. Sixteen animals in each group of the sham operation group, sepsis model group, and UC-MSCs treatment group were observed for 72-hour survival rate. The percentages of CD4(+) T cells and the ratio of helper T cells 1/2 (Th1/Th2) in whole blood cells were measured by flow cytometry at 12, 24, 48 and 72 hours after operation. The levels of tumor necrosis factor-α (TNF-α), high mobility group box 1 (HMGB1), interleukin-10 (IL-10) were measured by enzyme linked immunoabsorbent assay (ELISA).

RESULTS: The 72-hour survival rate of the UC-MSCs treatment group was slightly higher than that of the sepsis model group [62.5% (10/16) vs. 50.0% (8/16), χ (2) = 0.509, P > 0.05]. The percentage of CD4(+) T cells and Th1/Th2 ratio in the sepsis model group were significantly higher than those in the sham operation group at 12 hours after operation, and decreased as the time prolonged to 48 hours. The levels of plasma inflammatory factors were significantly higher than those of sham operation group at 12 hours after operation, TNF-α and IL-10 were decreased at 48 hours after operation, while HMGB1 continued to increase until 72 hours after operation. Compared with those in the sepsis model group, the percentages of CD4(+) T cells at 12 hours and 24 hours after operation [(49.66±0.91)% vs. (59.11±1.17)%, (41.80±0.89)% vs. (49.84±0.99)%], the levels of Th1/Th2 ratio at 12, 24, 48 hours after operation (0.745±0.065 vs. 1.254±0.115, 0.407±0.077 vs. 0.806±0.061, 0.280±0.057 vs. 0.454±0.049), and the levels of TNF-α and HMGB1 were significantly reduced at 12, 24, 48 and 72 hours after operation in the UC-MSCs treatment group [TNF-α (ng/L): 52.60±6.60 vs. 58.03±6.53, 71.77±8.48 vs. 147.39±11.37, 111.83±10.76 vs. 271.36±19.04, 83.09±7.43 vs. 171.04±14.06; HMGB1 (ng/L): 149.12±9.89 vs. 187.33±12.79, 192.94±14.92 vs. 442.35±52.72, 1 393.67±88.86 vs. 1 950.90±126.66, 1 875.84±111.67 vs. 2 557.12±186.01], all with statistically significant differences (all P < 0.05). The level of IL-10 was significantly higher at 12, 24, 48 and 72 hours after operation (ng/L: 65.46±5.51 vs. 33.32±4.17, 86.49±5.78 vs. 63.11±5.53, 142.73±9.94 vs. 106.81±6.36, 123.74±10.90 vs. 89.90±7.71, all P < 0.01).

CONCLUSIONS: UC-MSCs can make CD4(+) T cells in early sepsis, and Th1/Th2 ratio to normal, by reducing the levels of proinflammatory factors, and increasing the level of anti-inflammatory factor, and improve sepsis immune function status, but cannot improve the survival rate of animals.