Chinese Journal of Tissue Engineering Research ›› 2020, Vol. 24 ›› Issue (13): 2068-2073.doi: 10.3969/j.issn.2095-4344.2061

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Immunoregulation of allograft rejection: a role played by human CD200+ sub-population from human placenta-derived mesenchymal stem cells

Liu Ting, Yang Tingting, Ma Xiaona, Ma Haibin, Jin Yiran, Liang Xueyun   

  1. Ningxia Human Stem Cell Institute, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Received:2019-09-03 Revised:2019-09-05 Accepted:2019-10-21 Online:2020-05-08 Published:2020-03-10
  • Contact: Liang Xueyun, Associate researcher, Master’s supervisor, Ningxia Human Stem Cell Institute, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • About author:Liu Ting, Master, Assistant researcher, Ningxia Human Stem Cell Institute, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Supported by:
    the National Natural Science Foundation of China, No. 81460186

Abstract:

BACKGROUND: Immune rejection of skin allograft is a clinical problem to be solved. Our previous study has shown that human placenta-derived CD200+ mesenchymal stem cells may have a strong capability of immunoregulation.

OBJECTIVE: To investigate the effects of human placenta-derived CD200+ mesenchymal stem cells on rejection of skin allograft.

METHODS: Skin allograft models of c57/BL6 mice were established and divided into three groups as control group, human placenta-derived mesenchymal stem cells group (PMSCs group), and CD200+ mesenchymal stem cells group (CD200+-PMSCs group). PBS (control group), normal PMSCs and CD200+-PMSCs were injected into the mice through the tail vein, respectively. The necrotic time, survival time and situation of grafted skin were observed. The number of peripheral white blood cells was counted after 7 days of treatment. The expression levels of interleukin-10, interferon-γ and tumor necrosis factor-α were detected by Q-PCR and ELISA.

RESULTS AND CONCLUSION: (1) Compared with the control group, in the PMSCs and CD200+-PMSCs groups, the condition of skin allograft was better, and the survival time was significantly prolonged (P < 0.001). The condition and survival time of skin allograft in the CD200+-PMSCs group were significantly superior to those in the PMSCs group (P < 0.01). (2) After 7 days of treatment, the number of peripheral white blood cells in the PMSCs and CD200+-PMSCs groups was significantly less than that in the control group (P < 0.01). (3) Compared with the control group, the mRNA expression level of interleukin-10 in the spleen was significantly increased in the CD200+-PMSCs group (P < 0.05), and the mRNA expression levels of interferon-γ and tumor necrosis factor-α in the spleen were significantly down-regulated in the PMSCs and CD200+-PMSCs groups (P < 0.05, P < 0.01). The mRNA expression levels of interferon-γ and tumor necrosis factor-α in the spleen in the CD200+-PMSCs group were significantly lower than those in the PMSCs group (P < 0.01, P < 0.05). (4) Compared with the control group, the expression level of interleukin-10 in the blood was significantly increased (P < 0.05, P < 0.001), and the expression levels of interferon-γ and tumor necrosis factor-α in the blood were significantly down-regulated in the CD200+-PMSCs and PMSCs groups (P < 0.05, P < 0.001; P < 0.01, P < 0.001). The expression levels of interferon-γ and tumor necrosis factor-α in the blood in the CD200+-PMSCs group were significantly lower than those in the PMSCs group (P < 0.05). These results indicate that human placenta-derived mesenchymal stem cells have immunosuppressive effect on the rejection of skin allograft, and CD200+ cells may have better immunoregulatory effects by regulating the expressions of interleukin-10, interferon-γ and tumor necrosis factor-α.

Key words:  mesenchymal stem cells, placenta, CD200, cell sub-population, skin allograft, allograft rejection, immunosuppression, immunoregulation, cytokines

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