[Immunomodulatory effects of human placental-derived mesenchymal stem cells on immune rejection in mouse allogeneic skin transplantation].
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).


CONCLUSIONS
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.
Department of Medical Laboratory, Ningxia Medical University, Yinchuan Ningxia, 750004, P.R. China.
Qiong
Q
Wang
Ting
T
Liu
Yaolin
Y
Zhang
Dongmei
D
Chen
Libin
L
Wang
Yukui
Y
Li
Jun
J
Wei
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D056747:Immunomodulation; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000293:injuries; D016038:Skin Transplantation; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D020381:Interleukin-17; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma