Objective: To investigate the effect of human placental-derived mesenchymal stem cells (PMSCs) on immunological rejection in mouse allogeneic skin transplantation.
Methods: The placenta fetal tissues from voluntary donors were used to isolate and culture the PMSCs, and the 3rd passage PMSCs were used in the experiment. Thirty Vr: CD1 (ICR) mice at age of 1-2 days were used as skin donors for allogeneic skin transplantation. Thirty C57BL/6 mice at age of 6-8 weeks as recipients were made back skin defect of 12 mm in diameter and were randomly divided into 3 groups (n=10): group A, autograft; group B, allogeneic graft + PBS tail vein injection; and group C, allogeneic graft + human PMSCs (1 x 10(5) cells/mouse) tail vein injection. The flap survival was observed. At 7 days after skin transplantation, blood leukocyte counting, abdominal fluid macrophage activation, and the expression levels of interleukin 4 (IL-4), interleukin 17 (IL-17), and interferon gamma (INF-gamma) in blood and spleen were detected by ELISA and RT-PCR, respectively.
Results: The flap survival time was significantly longer in group A [(58.33 +/- 4.04) days] than in groups B and C [(3.80 +/- 0.92) days and (6.80 +/- 0.82) days] (P < 0.05), and in group C than in group B (P < 0.05). At 7 days after transplantation, the blood leukocyte number was (6.32 +/- 0.45) x 10(9)/L in group A, (7.45 +/- 0.52) x 10(9)/L in group B, and (6.35 +/- 0.39) x 10(9)/L in group C, and it was significantly more in group B than in groups A and C (P < 0.05). The macrophage activation rate of the abdominal fluid was 6.87% +/- 2.40% in group A, 7.84% +/- 0.44% in group B, and 15.98% +/- 2.87% in group C; group C was significantly higher than groups A and B (P < 0.01). ELISA results showed that there was no significant difference in the concentrations of IL-4 among 3 groups (P > 0.05). Compared with group B, the concentrations of IL-17 and IFN-gamma were significantly reduced in group C (P < 0.05), while the concentration of IFN-gamma was significantly increased in group B when compared with group A (P < 0.05). RT-PCR results showed that there were significant differences in the expressions of IL-4, IL-17, and IFN-gamma mRNA between groups B, C and group A (P < 0.05); the expressions of IL-4 and IFN-gamma mRNA were significantly lower in group C than in group B (P < 0.05).
Conclusion: Human PMSCs transplantation can suppress the acute immunological rejection in allogeneic skin transplantation. The possible mechanism may be partially related to the inhibitory effect on the secretion of IL-17 and IFN-gamma.