Department of Pathogenic Biology and Immunology, Medical School, Zhongda Hospital, Southeast University, Nanjing, People's Republic of China.
Biotechnol Appl Biochem. 2011 Nov-Dec;58(6):397-404. doi: 10.1002/bab.63. Epub 2011 Dec 2.
Ovarian cancer causes more deaths than any other cancer of the female reproductive system, and its overall cure rate remains low. The present study investigated human umbilical blood mononuclear cell (UBMC)-derived mesenchymal stem cells (UBMC-MSCs) as interleukin-21 (IL-21) gene delivery vehicles for ovarian cancer therapy in nude mice. MSCs were isolated from UBMCs and the expanded cells were phenotyped by flow cytometry. Cultured UBMCs were differentiated into osteocytes and adipocytes using appropriate media and then the UBMC-MSCs were transfected with recombinant pIRES2-IL-21-enhancement green fluorescent protein. UBMC-MSCs expressing IL-21 were named as UBMC-MSC-IL-21. Mice with A2780 ovarian cancer were treated with UBMC-MSC-IL-21 intravenously, and the therapeutic efficacy was evaluated by the tumor volume and mouse survival. To address the mechanism of UBMC-MSC-IL-21 against ovarian cancer, the expression of IL-21, natural killer glucoprotein 2 domain and major histocompatibility complex class I chain-related molecules A/B were detected in UBMC-MSC-IL-21 and in the tumor sites. Interferon-γ-secreting splenocyte numbers and natural killer cytotoxicity were significantly increased in the UBMC-MSC-IL-21-treated mice as compared with the UBMC-MSCs or the UBMC-MSC-mock plasmid-treated mice. Most notably, tumor growth was delayed and survival was prolonged in ovarian-cancer-bearing mice treated with UBMC-MSC-IL-21. Our data provide important evidence that UBMC-MSCs can serve as vehicles for IL-21 gene delivery and inhibit the established tumor.
卵巢癌导致的死亡人数超过女性生殖系统任何其他癌症，其总体治愈率仍然较低。本研究探讨了人脐血单核细胞（UBMC）衍生间充质干细胞（UBMC-MSCs）作为白细胞介素-21（IL-21）基因传递载体，用于裸鼠卵巢癌治疗。从 UBMC 中分离出 MSC，并通过流式细胞术对扩增后的细胞进行表型鉴定。使用合适的培养基将培养的 UBMC 分化为成骨细胞和脂肪细胞，然后用重组 pIRES2-IL-21-增强型绿色荧光蛋白转染 UBMC-MSCs。表达 IL-21 的 UBMC-MSCs 被命名为 UBMC-MSC-IL-21。用 A2780 卵巢癌细胞处理接受 UBMC-MSC-IL-21 静脉注射的小鼠，并通过肿瘤体积和小鼠存活来评估治疗效果。为了研究 UBMC-MSC-IL-21 对卵巢癌的作用机制，检测了 UBMC-MSC-IL-21 及肿瘤部位的 IL-21、自然杀伤糖蛋白 2 结构域和主要组织相容性复合体 I 链相关分子 A/B 的表达。与 UBMC-MSCs 或 UBMC-MSC-空载质粒处理的小鼠相比，UBMC-MSC-IL-21 处理的小鼠脾细胞分泌干扰素-γ的数量和自然杀伤细胞的细胞毒性明显增加。值得注意的是，用 UBMC-MSC-IL-21 治疗的卵巢癌荷瘤小鼠肿瘤生长延迟，存活时间延长。我们的数据提供了重要证据，表明 UBMC-MSCs 可作为 IL-21 基因传递载体，并抑制已建立的肿瘤。
