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首页> 外文期刊>Journal of Ovarian Research >Gene therapy of ovarian cancer using IL-21-secreting human umbilical cord mesenchymal stem cells in nude mice
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Gene therapy of ovarian cancer using IL-21-secreting human umbilical cord mesenchymal stem cells in nude mice

机译：分泌IL-21的人脐带间充质干细胞在裸鼠中的卵巢癌基因治疗

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Background The human umbilical cord mesenchymal stem cells (hUCMSCs) have the ability to migrate into tumors and therefore have been considered as an alternative source of mesenchymal progenitors for the therapy of malignant diseases. The present study was aimed to investigate effect of hUCMSCs as vehicles for a constant source of transgenic interleukin-21 (IL-21) on ovarian cancer in vivo. Methods The hUCMSCs were engineered to express IL-21 via lentiviral vector- designated ‘hUCMSCs-LV-IL-21’, and then were transplanted into SKOV3 ovarian cancer xenograft-bearing nude mice. The therapeutic efficacy and mechanisms of this procedure on ovarian cancer was evaluated. Results The isolated hUCMSCs were induced to differentiate efficiently into osteoblast and adipocyte lineages in vitro. The expressed IL-21 in the supernatant from hUCMSCs-LV-IL-21 obviously stimulated splenocyte’s proliferation. The hUCMSCs-LV-IL-21 significantly reduced SKOV3 ovarian cancer burden in mice indicated by tumor sizes compared with control mice. The expressed IL-21 not only regulated the levels of IFN-γ and TNF-α in the mouse serum but also increased the expression of NKG2D and MIC A molecules in the tumor tissues. The down regulation of β-catenin and cyclin-D1 in the tumor tissues may refer to the inhibition of SKOV3 ovarian cancer growth in mice. In addition, hUCMSCs did not form gross or histological teratomas up to 60 days posttransplantation in murine lung, liver, stomach and spleen. Conclusion These results clearly indicate a safety and usability of hUCMSCs-LV- IL-21 in ovarian cancer gene therapy, suggesting the strategy may be a promising new method for clinical treatment of ovarian cancer.
机译：背景技术人脐带间充质干细胞（hUCMSC）具有迁移到肿瘤中的能力，因此被认为是用于治疗恶性疾病的间充质祖细胞的替代来源。本研究旨在调查hUCMSCs作为体内恒定来源转基因白介素21（IL-21）的载体在卵巢癌中的作用。方法将hUCMSCs通过慢病毒载体“ hUCMSCs-LV-IL-21”表达IL-21，然后移植入SKOV3卵巢癌异种裸鼠中。评价了该方法对卵巢癌的治疗效果和机理。结果体外诱导的分离的hUCMSCs能有效分化为成骨细胞和脂肪细胞谱系。 hUCMSCs-LV-IL-21上清中表达的IL-21明显刺激了脾细胞的增殖。与对照小鼠相比，hUCMSCs-LV-IL-21显着降低了肿瘤大小指示的小鼠SKOV3卵巢癌负担。表达的IL-21不仅调节小鼠血清中IFN-γ和TNF-α的水平，而且还增加了肿瘤组织中NKG2D和MICA分子的表达。肿瘤组织中β-catenin和cyclin-D1的下调可能是抑制SKOV3卵巢癌小鼠的生长。此外，hUCMSCs移植后60天在鼠肺，肝，胃和脾脏中均未形成肉眼或组织学畸胎瘤。结论这些结果清楚地表明了hUCMSCs-LV-IL-21在卵巢癌基因治疗中的安全性和可用性，表明该策略可能是一种有前景的卵巢癌临床治疗新方法。

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