摘要
目的 探讨CIK细胞对肿瘤组织的靶向性及其在荷瘤鼠体内的运行轨迹和对主要脏器的影响。方法 分离制备人CIK细胞,采用体外Transwell迁移试验观察CIK细胞对人乳腺癌细胞MDA-MB-435的靶向迁移效应; 以该细胞系接种BALB/c裸鼠建立乳腺癌移植瘤模型,尾静脉注射DiI标记的CIK细胞,应用活体成像和病理学检查观察CIK细胞运行轨迹及对主要脏器的影响。结果 CIK细胞在体外培养14～20天时,细胞增殖达到高峰,CD3＋CD56＋ T细胞的比例也达到最高值。体外Transwell迁移实验显示,随着肿瘤细胞上清液浓度的增加,CIK细胞的迁移数量也随之增多。荷瘤裸鼠尾静脉注射DiI标记的CIK细胞后,活体成像显示肿瘤组织24 h开始出现荧光信号,48 h达到最强; HE和免疫组化染色结果显示,注射后6 h肿瘤周围开始聚集CIK细胞,48 h最多,第14天时肿瘤部位仍有CIK细胞存在,各脏器均未发现由CIK细胞导致的病理组织学损伤。结论 CIK细胞在体内外对肿瘤组织均具有靶向性,对正常组织有安全性,可作为一种有潜力的细胞载体应用于肿瘤的靶向治疗。
Purpose To evaluate the tumor tropism of cytokine-induced killer （CIK） cells, the movement track in nude mice bearing breast carcinoma and the influence on major organs of nude mice. Methods Separated and prepared CIK cells using human peripheral blood. The transwell migration assay was used to study the migratory response of CIK cells to human MDA-MB-435 breast carcinoma cells. A nude mouse xenograft model （BALB/c） was established by injection of human MDA-MB-435 breast carcinoma cells. CIK cells labelled with DiI were injected into caudal vein of the nude mice bearing transplantation tumor. Movement track of CIK cells in vi- vo and influence on major organs were observed by living imaging technology, histopathology and immunohistopathology. Results When cultured in vitro during 14 - 20 days, CIK cells reached the peak level in proliferating stage with the maximum proportion of CD3^＋ CD56^＋ T cells. Transwell migration assay showed that the migrating number of CIK cells was increasing along with the increasing concentration of tumor cell cultural supernatants. Living imaging technology showed that the fluorescence signal began to appear 24 hours after injection of CIK cells and was strongest at 48 hours. Immunohistochemical technique and hematoxylin-eosin stain showed CIK cells tended to gather around tumor tissue 6 hours after injection, the most at 48 hours, and with some of the remaining ceils on 14 day. In the meantime, no pathological damage caused by CIK cells was observed. Conclusion CIK cells have good tropism to the tumor tissue and safety to the normal tissue, and could be used as a promising cell vector for targeted therapy of cancer.
出处
《临床与实验病理学杂志》
CAS
CSCD
北大核心
2014年第4期360-365,共6页
Chinese Journal of Clinical and Experimental Pathology
基金
国家自然科学基金面上项目(30872994)
云南省应用基础研究计划重点项目(2013FA059)
