人脐带间充质干细胞对裸鼠的促瘤和致瘤性研究

发布时间：2018-10-20 11:49

【摘要】：目的研究人脐带间充质干细胞(hUCMSCs)对动物是否具有促瘤性,以及不同代次是否有致瘤性,为其临床应用提供安全性依据。方法分别用人淋巴瘤细胞Raji接种于CB-17 SCID小鼠皮下、用人结肠癌细胞WiDr接种于BALB/c裸鼠皮下,建立皮下移植瘤模型,WiDr成模动物用完全随机法分为4组(n=8):模型对照组、hUCMSCs低、中、高剂量组;Raji成模动物用完全随机法分为5组(n=7):空白对照组、模型对照组、hUCMSCs低、中、高剂量组。hUCMSCs均静脉注射给药,观察hUCMSCs对皮下移植瘤的增殖是否有影响。另外,观察不同代次的hUCMSCs是否有致瘤性,NOD/SCID小鼠分别皮下接种hUCMSCs的第2、6、10代的细胞,注射后3周,16周对动物剖检,观察hUCMSCs皮下结节的形成及是否有肿瘤转化的倾向。对照组和hUCMSCs组的瘤体积及瘤重采用成组t检验进行统计分析,并计算hUCMSCs组相比对照组的相对肿瘤抑制率T/C%。结果 WiDr肿瘤模型中,第43天hUCMSCs中、高剂量组的瘤体积均显著低于模型对照组,分别为(586.7±274.4)mm~3、(689.5±114.8)mm~3 vs(945.9±234.0)mm~3,P0.05,但T/C%值40%;第51天hUCMSCs低、中高剂量组瘤体积均显著低于模型对照组,分别为(777.8±346.7)mm~3、(793.1±358.6)mm~3、(800.7±116.5)mm~3 vs(1300.0±356.8)mm~3,P均0.05,但T/C%值均40%;表明hUCMSCs在3个剂量下均未对WiDr肿瘤的生长有影响,无显著促进或抑制作用。Raji肿瘤模型中,hUCMSCs治疗组瘤体积与对照组相比在所有时间点差异均无统计学意义(P0.05),显示hUCMSCs在本实验条件下对肿瘤生长没有明显的抑制和促进作用。两个模型的病理检测均未见对肿瘤增殖有明显影响。3个不同代次的hUCMSCs注射到NOD/SCID后16周对动物剖检,也没有观察到肿瘤转化的倾向。结论 hUCMSCs对裸鼠WiDr和Raji移植瘤模型的肿瘤增殖无促进作用,不同代次的hUCMSCs在NOD/SCID裸鼠体内移植也不具有致瘤性。
[Abstract]:Objective to study whether human umbilical cord mesenchymal stem cell (hUCMSCs) is tumor-promoting in animals and whether different generations have tumorigenicity, so as to provide a safe basis for clinical application of human umbilical cord mesenchymal stem cell (hUCMSCs). Methods Human lymphoma cell line Raji was inoculated subcutaneously into CB-17 SCID mice and human colon cancer cell WiDr was inoculated into BALB/c nude mice to establish subcutaneous transplanted tumor model. WiDr model animals were randomly divided into 4 groups (nun8): model control group, low and middle hUCMSCs. The model animals of Raji were randomly divided into 5 groups: blank control group, model control group, hUCMSCs low, middle and high dose groups. HUCMSCs was injected intravenously to observe the effect of hUCMSCs on the proliferation of subcutaneous transplanted tumor. In addition, we observed whether hUCMSCs of different generations had tumorigenicity or not. NOD/SCID mice were inoculated subcutaneously with the cells of hUCMSCs 2 ~ 6 ~ (6) ~ (10). The animals were dissected 3 weeks and 16 weeks after injection, and the formation of hUCMSCs subcutaneous nodules and the tendency of tumor transformation were observed. The tumor volume and tumor weight in the control group and the hUCMSCs group were statistically analyzed by group t test, and the relative tumor inhibition rate (T / C) of the hUCMSCs group was calculated compared with that of the control group. Results in the WiDr tumor model, the tumor volume of the high dose group was significantly lower than that of the model control group on the 43rd day of hUCMSCs, which was (586.7 卤274.4) mm~3, (689.5 卤114.8) mm~3 vs (945.9 卤234.0) mm~3,P0.05, but 40% T / C%, and on the 51st day, the tumor volume in the low and middle dose group was significantly lower than that in the model control group. The values of (777.8 卤346.7) mm~3, (793.1 卤358.6) mm~3, (800.7 卤116.5) mm~3 vs (1300.0 卤356.8) mm~3,P were 0.05, but the values of T / C% were 40, indicating that hUCMSCs had no effect on the growth of WiDr tumor at three doses. In the Raji tumor model, there was no significant difference in tumor volume between the hUCMSCs group and the control group at all time points (P0.05), indicating that hUCMSCs had no obvious inhibition and promotion on tumor growth under this experimental condition. The pathological examination of the two models showed no significant effect on the proliferation of the tumor, and no tendency of tumor transformation was observed 16 weeks after the injection of three generations of hUCMSCs into NOD/SCID. Conclusion hUCMSCs has no effect on tumor proliferation of WiDr and Raji transplanted tumor models in nude mice, nor does hUCMSCs transplantation in NOD/SCID nude mice.
【作者单位】： 北科生物科技有限公司;昭衍新药研究中心股份有限公司;
【基金】：深圳市科技计划项目(JSGG20130917151830203)
【分类号】：R329.2

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