骨髓间充质干细胞对高转移肝癌模型的干预

Bone marrow-derived mesenchymal stem cells for high-metastatic potential hepatocellular carcinoma

背景:骨髓间充质干细胞具备化学趋向性和归巢作用,对于促进患者免疫系统的重建、消除残留病灶及防止复发转移具有良好的效果。目的:观察人骨髓间充质干细胞移植入动物模型对肝癌组织的影响情况及对肝癌转移潜能影响。方法:制作高转移潜能动物模型,实验组在接种肿瘤后第7日开始尾静脉注射骨髓间充质干细胞,5×105/次,2次/周;对照组尾静脉注射骨髓间充质干细胞培养液,0.2 mL/次,实验开始后每4 d用测量肿瘤体积,肿瘤接种后14 d(2周),21 d(3周),28 d(4周),35 d(5周),42 d(6周)处死动物,称质量,取瘤块,称瘤质量,计算肿瘤质量抑制率。PCR检测动物模型标本转移相关因子骨桥蛋白、骨唾液蛋白、整合素αⅤ基因的表达,及肿瘤标本凋亡相关因子bcl-2、bax、caspase3基因的表达。结果与结论:第3周时肿瘤的质量抑制率效果最好,随着时间的延长,肿瘤的抑制率逐渐下降。肝癌转移相关的生物学指标均呈逐渐下降趋势,代表肿瘤凋亡指标的因子呈两极分化表现,抗凋亡bcl-2因子呈逐渐下降的趋势,凋亡因子bax、caspase3呈逐渐升高的趋势。骨髓间充质干细胞对肝癌动物模型肿瘤抑制效能随时间而变化,骨髓间充质干细胞移植后第3周对肝癌抑制效果最显著,随着时间的延长,抑制效能减弱。骨髓间充质干细胞对肝癌的转移潜能具有抑制作用。

BACKGROUND：Bone marrow mesenchymal stem cells have the chemotaxis and homing role that promotes immune system reconstruction, eliminate residual lesions and prevent recurrence in patients. OBJECTIVE：To observe therapeutic effect of human bone marrow mesenchymal stem cells transplantation into high-metastatic potential hepatocellular carcinoma animal models on metastatic potential of high-metastatic potential hepatocellular carcinoma. METHODS：Nude mouse models of high-metastatic potential hepatocellular carcinoma were established in vivo. In the experimental group, 5×105 cells were injected via the tail vein on day 7 after tumor inoculation, twice a week. In the control group, cellculture medium, 0.2 mL per mouse, was injected by the tail vein. After the start of the experiment, tumor volume was measured every 4 days. After tumor inoculation for 14 days, 21 days, 28 days, 35 days, 42 days, animal models were sacrificed, and then tumor mass and body mass were recorded to calculate the inhibition rate. PCR was employed to detect osteopontin, bone sialoprotein, and integrinα Ⅴ mRNA expression, as wel as bcl-2, bax, caspase3 mRNA expression. RESULTS AND CONCLUSION：The inhibition rate of tumor mass showed the best results in week 3. As time went on, the tumor inhibition rate was gradual y decreased. Metastasis-related biological factors showed a gradual down-regulated trend, indicating the polarization of tumor apoptotic indexes, that is, anti-apoptotic factor, bcl-2, showed a decreasing trend, while apoptotic factors, bax and caspase3, appeared to have a gradual y increased trend. These findings suggest that human bone marrow mesenchymal stem cells effects to inhibit high-metastatic potential hepatocellular carcinoma animal models appear to vary with time. After human bone marrow mesenchymal stem cells transplantation for 3 weeks, the inhibition performance on high-metastatic potential hepatocellular carcinoma is the best, and then it weakens with time. Human bone marrow mesenchymal stem cells are found to inhibit the metastatic potential of hepatocellular carcinoma.