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目的:研究人脐带间质干细胞(UCMSC)对Wistar大鼠的免疫毒性作用。方法:SPF级Wistar大鼠112只分为4组:溶媒组(给予溶媒5 ml/kg)、低剂量组(给予人UCMSC 1×107个/kg)、高剂量组(给予人UCMSC 5×107个/kg)和对照组(给予大鼠UCMSC 1×107个/kg)。每组28只大鼠,雌雄各14只。大鼠尾静脉注射给药,2周1次,共注射4次。给UCMSC后每周进行受体鼠临床移植物抗宿主病(GVHD)评分,末次注射UCMSC后1、13周检测血IgG、IgM含量,CD3+、CD4+、CD8+T细胞数量,并对大鼠淋巴结、胸腺、脾脏进行脏器系数计算和组织病理学检查。结果:给予UCMSC后,各组大鼠的GVHD评分值均为0。末次给予UCMSC后1周,低、高剂量组雌性大鼠IgG[(0.65±0.12)、(0.63±0.14)g/L]和IgM含量[(0.06±0.01)、(0.06±0.01)g/L]明显高于溶媒组雄性大鼠[(0.41±0.17)g/L、(0.04±0.01)g/L,P<0.01或P<0.05];高剂量组雄性大鼠IgM含量[(0.05±0.01)g/L]明显高于溶媒组雄性大鼠[(0.03±0.01)g/L,P<0.01];对照组雌性、雄性大鼠IgM[(0.06±0.02)、(0.05±0.02)g/L]也明显高于溶媒组(P<0.01或P<0.05)。末次给予UCMSC后13周,各剂量组雌、雄性大鼠IgG、IgM与溶媒组相比差异均无统计学意义(均P>0.05)。末次给予UCMSC后1周,低、高剂量组雌性大鼠的脾脏系数[分别为(0.274±0.016)%、(0.294±0.019)%]明显高于溶媒组[(0.232±0.012)%,P<0.01];高剂量组雄性大鼠的脾脏系数[(0.242±0.027)%]明显高于溶媒组[(0.202±0.012)%,P<0.01];对照组雌、雄性大鼠脾脏系数[分别为(0.261±0.019)%、(0.236±0.014)%]也明显高于溶媒组(P<0.05或P<0.01)。末次给予UCMSC后13周各组大鼠的脾脏和胸腺系数差异均无统计学意义(均P>0.05)。各组大鼠CD3+、CD4+、CD8+T细胞百分比及CD4+/CD8+比值均在正常范围内。各组大鼠胸腺、脾脏和肠系膜淋巴结组织病理学检查均未见明显异常。结论:人脐带间质干细胞可引起正常Wistar大鼠免疫球蛋白含量和脾脏系数的升高,该作用具有一过性和可逆性。
Objective: To study the immunotoxicity of human umbilical cord mesenchymal stem cells (UCMSC) on Wistar rats. Methods: One hundred and twelve SPF Wistar rats were divided into four groups: vehicle group (given 5 ml / kg vehicle), low dose group (given human UCMSC 1 × 107 cells / kg), high dose group (given human UCMSC 5 × 107 Kg / kg) and a control group (1 × 107 rats / kg for UCMSCs administered to rats). Each group of 28 rats, 14 male and one female. Rats intravenous injection, 1 week 2 times, a total of 4 times. The clinical graft-versus-host disease (GVHD) scores of recipient mice were evaluated weekly after UCMSC. The levels of serum IgG, IgM, CD3 +, CD4 + and CD8 + T cells were measured at 1 and 13 weeks after the last injection of UCMSC. , Thymus, spleen organ coefficient calculation and histopathological examination. Results: After administration of UCMSC, the GVHD scores of all the rats in each group were 0. At 1 week after the last administration of UCMSC, the levels of IgG [(0.65 ± 0.12) and (0.63 ± 0.14) g / L] and IgM in low and high dose groups [(0.06 ± 0.01) and (0.06 ± 0.01) g / ] Was significantly higher than that of the male rats in the vehicle group [(0.41 ± 0.17) g / L, (0.04 ± 0.01) g / L, P <0.01 or P < (0.06 ± 0.02), (0.05 ± 0.02) g / L] in the male and female rats in the control group [(0.03 ± 0.01) g / L, L] was also significantly higher than the vehicle group (P <0.01 or P <0.05). At the 13th week after the last administration of UCMSC, there was no significant difference in the IgG and IgM levels between the female and male rats in each dose group and the vehicle group (all P> 0.05). One week after the last administration of UCMSC, the spleen coefficient [(0.274 ± 0.016)% and (0.294 ± 0.019)%] in the low and high dose groups were significantly higher than those in the vehicle group [(0.232 ± 0.012)%, P < 0.01). The spleen coefficient (0.242 ± 0.027)% in the high dose group was significantly higher than that in the vehicle group (0.202 ± 0.012)%, P <0.01. The spleen coefficient in the male and female rats in the control group were (0.261 ± 0.019)%, (0.236 ± 0.014)%] were also significantly higher than those in the vehicle group (P <0.05 or P <0.01). There was no significant difference in the coefficient of spleen and thymus between the rats of the 13th week after the last administration of UCMSC (all P> 0.05). The percentage of CD3 +, CD4 +, CD8 + T cells and CD4 + / CD8 + ratio in each group were within the normal range. The thymus, spleen and mesenteric lymph node histopathological examination showed no obvious abnormalities in all groups. Conclusion: Human umbilical cord mesenchymal stem cells can cause normal Wistar rats immunoglobulin content and spleen coefficient increased, the role of a transient and reversible.