【摘要】：目的研究人臍帶間充質(zhì)干細(xì)胞(hUCMSCs)對(duì)動(dòng)物是否具有促瘤性,以及不同代次是否有致瘤性,為其臨床應(yīng)用提供安全性依據(jù)。方法分別用人淋巴瘤細(xì)胞Raji接種于CB-17 SCID小鼠皮下、用人結(jié)腸癌細(xì)胞WiDr接種于BALB/c裸鼠皮下,建立皮下移植瘤模型,WiDr成模動(dòng)物用完全隨機(jī)法分為4組(n=8):模型對(duì)照組、hUCMSCs低、中、高劑量組;Raji成模動(dòng)物用完全隨機(jī)法分為5組(n=7):空白對(duì)照組、模型對(duì)照組、hUCMSCs低、中、高劑量組。hUCMSCs均靜脈注射給藥,觀察hUCMSCs對(duì)皮下移植瘤的增殖是否有影響。另外,觀察不同代次的hUCMSCs是否有致瘤性,NOD/SCID小鼠分別皮下接種hUCMSCs的第2、6、10代的細(xì)胞,注射后3周,16周對(duì)動(dòng)物剖檢,觀察hUCMSCs皮下結(jié)節(jié)的形成及是否有腫瘤轉(zhuǎn)化的傾向。對(duì)照組和hUCMSCs組的瘤體積及瘤重采用成組t檢驗(yàn)進(jìn)行統(tǒng)計(jì)分析,并計(jì)算hUCMSCs組相比對(duì)照組的相對(duì)腫瘤抑制率T/C%。結(jié)果 WiDr腫瘤模型中,第43天hUCMSCs中、高劑量組的瘤體積均顯著低于模型對(duì)照組,分別為(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、中高劑量組瘤體積均顯著低于模型對(duì)照組,分別為(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個(gè)劑量下均未對(duì)WiDr腫瘤的生長(zhǎng)有影響,無(wú)顯著促進(jìn)或抑制作用。Raji腫瘤模型中,hUCMSCs治療組瘤體積與對(duì)照組相比在所有時(shí)間點(diǎn)差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),顯示hUCMSCs在本實(shí)驗(yàn)條件下對(duì)腫瘤生長(zhǎng)沒(méi)有明顯的抑制和促進(jìn)作用。兩個(gè)模型的病理檢測(cè)均未見(jiàn)對(duì)腫瘤增殖有明顯影響。3個(gè)不同代次的hUCMSCs注射到NOD/SCID后16周對(duì)動(dòng)物剖檢,也沒(méi)有觀察到腫瘤轉(zhuǎn)化的傾向。結(jié)論 hUCMSCs對(duì)裸鼠WiDr和Raji移植瘤模型的腫瘤增殖無(wú)促進(jìn)作用,不同代次的hUCMSCs在NOD/SCID裸鼠體內(nèi)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 鹵274.4) mm~3, (689.5 鹵114.8) mm~3 vs (945.9 鹵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 鹵346.7) mm~3, (793.1 鹵358.6) mm~3, (800.7 鹵116.5) mm~3 vs (1300.0 鹵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.
【作者單位】： 北科生物科技有限公司;昭衍新藥研究中心股份有限公司;
【基金】：深圳市科技計(jì)劃項(xiàng)目(JSGG20130917151830203)
【分類號(hào)】：R329.2

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