背景:目前脐带、胎盘间充质干细胞在一些急性移植物抗宿主病(graft versus host disease,GVHD)临床实验及动物模型中展现了良好的预防效果,但两种干细胞哪一个对GVHD的治疗更为有效尚无文献报道。目的:观察比较人脐带和胎盘间充质干细胞的免疫调节功能,以及对小鼠急性GVHD的预防作用。方法:(1)体外实验:取人外周血单个核细胞,分4组培养,单独培养组、植物凝集素组、植物凝集素联合脐带间充质干细胞组、植物凝集素联合胎盘间充质干细胞组。5 d后,检测外周血单个核细胞增殖及培养上清干扰素γ分泌水平;(2)动物体内实验:取BABL/c(H-2d)小鼠57只,8.5 Gy全身照射后分6组,单纯照射组尾静脉注射生理盐水0.5 mL;同基因脊髓移植组尾静脉注射同种异体骨髓有核细胞悬液0.5 mL;异基因骨髓移植组尾静脉注射异种骨髓有核细胞悬液0.5 mL;急性GVHD组尾静脉注射异种骨髓有核细胞与脾脏单个核细胞混合液0.5 mL;脐带干细胞组尾静脉注射异种骨髓有核细胞、脾脏单个核细胞与人脐带间充质干细胞混合液0.5 mL;胎盘干细胞组尾静脉注射异种骨髓有核细胞、脾脏单个核细胞与人胎盘间充质干细胞混合液0.5 mL。移植后11 d,进行GVHD临床症状评分;移植后3周,进行生存时间分析;移植后2周,进行皮肤、肝脏及小肠病理组织学分析。结果与结论:(1)体外实验:与脐带间充质干细胞相比,胎盘间充质干细胞具有更强的抗炎功能;(2)动物体内实验:脐带干细胞组、胎盘干细胞组GVHD临床症状评分低于急性GVHD组(P〈0.05),小鼠存活率高于急性GVHD组(P〈0.05)。急性GVHD组、胎盘间充质干细胞组和脐带间充质干细胞组均未发生皮肤组织病变,各组均可见小肠组织黏膜脱落病变,组间差异不明显;急性GVHD组小鼠肝脏组织可见多发性灶性坏死和大量炎症细胞浸润,胎盘干细胞组?
BACKGROUND: Recently, the effects of human umbilical cord mesenchymal stem cells(h UCMSCs) and placenta-derived mesenchymal stem cells(PDMSCs) on treatment of acute graft versus host disease(a GVHD) have been confirmed in some in vitro studies or animal models. But there are still no reports comparing the therapeutic effects of these two cell types.OBJECTIVE: To compare the immunosuppressive function of h UCMSCs and PDMSCs in vitro or in a mouse a GVHD model. METHODS:(1) In vitro experiment. Human peripheral blood mononuclear cells(PBMCs) were isolated and divided into four groups: PBMCs cultured alone, PBMCs stimulated with phytohaemagglutinin(PHA), PHA stimulated-PBMCs cocultured with h UCMSCs, PHA stimulated-PBMCs cocultured with PDMSCs. After 5 days, PBMCs proliferation and interferon-γ level in cell 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 groups: only saline injection group, syngeneic bone marrow transplantation group, allogeneic bone marrow transplantation group, a GVHD group, h UCMSCs treatment group, PDMSCs treatment group. The clinical a GVHD score, histopathology of skin, liver, and small intestine, and survival time were analyzed at days 11, 14, 21 after transplantation. RESULTS AND CONCLUSION:(1) In vitro test: compared with the h UCMSCs, PDMSCs had stronger anti-inflammatory function.(2) In vivo test: The clinical scores on acute graft versus host disease were significantly lower in the h UCMSCs and PDMSCs treatment groups than that in the a GVHD group(P〈0.05). The survival rates of mice were significantly increased in the h UCMSCs and PDMSCs treatment groups compared to the a GVHD group(P〈0.05). Evident skin lesions were not found in all groups. Although small intestine mucosal lesions were found in all groups, the damage level seemed similar. Notably, significant difference was found in the liver that multifocal necrosis and a lar