摘要
目的通过阻断正常干细胞的分化过程,探讨肿瘤发生机制。方法利用贴壁培养法获得大鼠骨髓间充质干细胞(BMSCs),通过地塞米松、胰岛素和吲哚美辛联合诱导大鼠BMSCs,使其分化为脂肪细胞。在细胞分化过程中利用3-甲基胆蒽(3-MC)阻断大鼠BMSCs的分化过程。结果大鼠BMSCs分化实验结果显示,诱导30d后,经油红O染色,细胞内可见脂肪细胞特有的红色脂滴沉淀,且随着诱导时间的延长,油红O阳性细胞比例增加,脂滴增大,表明大鼠BMScs已成功分化为脂肪细胞。大鼠BMSCs分化阻断实验结果显示,诱导30d后,经油红O染色,细胞内红色脂滴沉淀明显下降,表明阻断后的细胞具有脂肪细胞的特性,但分化不完全;形态学鉴定表现为细胞接触抑制消失、细胞核异常、微核畸变率高和核型异常,表明阻断后的干细胞发生恶性转变。结论大鼠BMSCs分化过程受到阻断,细胞停止在分化的中间阶段,有转化为肿瘤细胞的趋势。
Objective To explore the pathogenesis of tumors by blocking the normal differentiation process of stem cells. Methods Bone marrow mesenehymal stem cells (BMSCs) from rats were isolated, cultured and purified by whole bone marrow adherence method. The rat BMSCs were induced to differentiate into adipecytes with dexamethasone, insulin and indomethacin. Blockage of the differentiation process was induced by 3-methylcholanthrene (3-MC). Results The differentiation experiment showed that at 30 days after the induction, oil red O staining-positive cells occurred with increased intracytolasmie lipid droplets, characteristic for adipocytes. The differentiation blockage experiment showed that at 30 days after induction, the deposits of oil red O staining-cytoplasmic lipid droplets was significantly reduced, indicating that the blocked eells were adipecytes, but not fully differentiated. Morphological identification showed that cell contact inhibition disappeared, abnormal cell nuclei, increased number of micronucleus aberration and karyotype abnormalities, indicating that malignant transformation of the stem cells occurred after the differentiation blockage. Conclusions The results of this study show a blockage of the differentiation of that stem cells at the intermediate phase, and a tendency of malignant transformation of the stem cells. The results of our study provide new evidence that cancer stem cells may be originated by suppression of stem cell differentiation.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2012年第11期826-830,共5页
Chinese Journal of Oncology
关键词
骨髓间充质干细胞
脂细胞
诱导
细胞分化
大鼠
Bone marrow mesenchymal stem cells
Adipocytes
Induction
Celldifferentiation
Rat