人脾原发性恶性淋巴瘤裸小鼠原位移植模型的建立及生物学特性的研究

Establishment and characteristics of orthotopically transplanted model of human primary malignant spleen lymphoma in nude mice

目的 建立人脾原发性恶性淋巴瘤裸小鼠原位移植模型 ,为探讨其发病机理和实验治疗提供工具。方法 将 11例人脾原发性恶性淋巴瘤新鲜组织植入裸鼠脾实质内 ,观察原位移植的成瘤、移植瘤的侵袭和转移及其形态学特征 (光镜、电镜、免疫组织化学 )。结果 筛选出 1株人脾原发性 (非霍奇金B细胞性裂核细胞型 )恶性淋巴瘤裸鼠原位移植模型 (BFNHL HMN 1) ,已传至 41代 ;1株人脾原发性 (非霍奇金B细胞性裂核细胞型 )恶性淋巴瘤裸鼠原位移植肝转移模型 (LM BFNHL HMN 2 ) ,已传至 47代 ;1株人脾原发性 (非霍奇金T免疫母细胞 )恶性淋巴瘤裸鼠原位移植模型 (TINHL HMN 3) ,已传至 37代。共移植裸鼠 6 11只 ,其肿瘤移植生长率、肝转移率和液氮冻存复苏成活率均为10 0 %。BFNHL HMN 1和TINHL HMN 3肿瘤完全限于脾内 ,呈结节状生长 ,或伴有脾门淋巴结累及 ,无腹腔淋巴结和器官转移。LM BFNHL HMN 2肿瘤不仅限于脾脏 ,并有脾门淋巴结及肝转移。原位移植瘤组织经病理学、超微结构观察、流式细胞仪DNA含量测定及染色体核型的分析 ,表明与人脾原发性恶性淋巴瘤细胞相一致。结论 所建立的 3株人脾原发性恶性淋巴瘤裸鼠原位移植模型 ,完整地模拟了人脾原发性恶性淋巴瘤患者的临床过程 。

Objective To establish three orthotopically transplanted model of human primary malignant spleen lymphoma in the nude mice. Methods Orthotopic transplantation of histologically intact human primary malignant splenic lymphoma tissue obtained from patients was introduced into the splenic parenchyma of nude mice. Tumorigenicity, invasion, metastasis and morphological characteristics of the transplanted tumor were studied by light microscopy, electron microscopy and immunohistochemical methods. Results The first kind, a strain of human primary malignant spleen lymphoma (non-Hodgkin′s, cleaved B cell, BFNHL-HMN-1) screened from 11 patients which had been passaged in vivo for 41 generations, a second kind, a liver metastasis model of human primary malignant spleen lymphoma (non-Hodgkin′s, cleaved B cell, LM-BFNHL-HMN-2) which had been passaged for 47 generations and a third kind of human primary malignant spleen lymphoma (non-Hodgkin′s, T-immunoblastic cell, TINHL-HMN-3) having passaged for 37 generations were all successfully tiansplanted in 611 nude mice. Models of BFNHL-HMN-1 and TINHL-HMN-3 tumor gave nodular growth and lymphnode metastasis in the spleen hilum but without any metastasis in the abdominal lymphnodes or organs. In the LM-BFNHL-HMN-2 model, not only did the tumor cells grow in the spleen, but in spleen hilum, lymphnodes and liver also. The orthotopically transplanted tumor cells were similar to the original human tumor in light histopathology, ultrastructure features, DNA content and chromosomal karyotype. Conclusion These three models are able to serve as useful tools for the study of biologic characteristics and experimental treatment of human primary malignant lymphoma.