Effect of human umbilical cord versus placenta mesenchymal stem cells in prevention of mouse acute graft versus host disease / 中国组织工程研究

ABSTRACT

BACKGROUND:Recently, the effects of human umbilical cord mesenchymal stem cel s (hUCMSCs) and placenta-derived mesenchymal stem cel s (PDMSCs) on treatment of acute graft versus host disease (aGVHD) have been confirmed in some in vitro studies or animal models. But there are stil no reports comparing the therapeutic effects of these two cel types. OBJECTIVE:To compare the immunosuppressive function of hUCMSCs and PDMSCs in vitro or in a mouse aGVHD model. METHODS:(1) In vitro experiment. Human peripheral blood mononuclear cel s (PBMCs) were isolated and divided into four groupsPBMCs cultured alone, PBMCs stimulated with phytohaemagglutinin (PHA), PHA stimulated-PBMCs cocultured with hUCMSCs, PHA stimulated-PBMCs cocultured with PDMSCs. After 5 days, PBMCs proliferation and interferon-γlevel in cel supernatant were measured. (2) In vivo experiment. Fifty-seven BABL/C(H-2d) mice exposed to 8.5 Gy irradiation were randomly divided into five groupsonly saline injection group, syngeneic bone marrow transplantation group, al ogeneic bone marrow transplantation group, aGVHD group, hUCMSCs treatment group, PDMSCs treatment group. The clinical aGVHD score, histopathology of skin, liver, and smal intestine, and survival time were analyzed at days 11, 14, 21 after transplantation. RESULTS AND CONCLUSION:(1) In vitro testcompared with the hUCMSCs, PDMSCs had stronger anti-inflammatory function. (2) In vivo testThe clinical scores on acute graft versus host disease were significantly lower in the hUCMSCs and PDMSCs treatment groups than that in the aGVHD group (P<0.05). The survival rates of mice were significantly increased in the hUCMSCs and PDMSCs treatment groups compared to the aGVHD group (P<0.05). Evident skin lesions were not found in al groups. Although smal intestine mucosal lesions were found in al groups, the damage level seemed similar. Notably, significant difference was found in the liver that multifocal necrosis and a large number of inflammatory cel s were seen in the aGVHD group, but less necrosis and inflammatory cel s in the hUCMSC and PDMSC treatment groups. In conclusion, hUCMSC and PDMSC are comparably effective in the treatment of aGVHD in mice.