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间质干细胞支持递送并提高溶瘤呼肠孤病毒在 TC-1 肿瘤细胞中的疗效。

Mesenchymal stem cells support delivery and boost the efficacy of oncolytic reoviruses in TC-1 tumor cells.

机构信息

Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

J Cell Biochem. 2021 Oct;122(10):1360-1375. doi: 10.1002/jcb.29955. Epub 2021 May 30.

Abstract

Cancer has remained a major health problem around the world. Mesenchymal stem cells (MSCs)-based therapy exhibits a therapeutic effect via different mechanisms. By using MSCs as carrier cells, the major problem of clearance of oncolytic viruses is resolved by neutralizing antibodies before they react with cancer cells. The aim of this study was to characterize the effect of infected MSCs by reovirus type-3 Dearing (T3D) for in vitro cancer therapy. Adipose-derived MSCs (AD-MSCs) were infected with reovirus T3D and its biological properties were evaluated. Then, the effects of reovirus-infected AD-MSCs on cytokine profile, nitric oxide (NO) production, and apoptosis induction in TC-1 cells were assessed. Our results indicated that the differentiation potential of AD-MSCs was affected by reovirus. However, phenotypes were not affected after infection. Then, the effects of reovirus-infected AD-MSCs in TC-1 cells showed an increased amount of tumor necrosis factor-alpha (TNF-α) and NO production and a decreased amount of transforming growth factor-beta 1 (TGF-β1) and interleukin-10 (IL-10). Moreover, apoptosis significantly increased via coculturing of TC-1 cells with infected AD-MSCs, compared with control, and both internal and external apoptosis pathways are activated in experimental groups. In conclusion, the data showed that with increasing TNF-α and NO production and reducing IL-10 and TGF-β production, AD-MSCs can enhance the oncolytic effect of reovirus in cancer cells. Furthermore, the results suggested that AD-MSCs can be used as effective carrier cells candidate for reovirus T3D to maximize their anticancer cell activity.

摘要

癌症仍然是全球主要的健康问题。间充质干细胞(MSCs)为基础的治疗通过不同的机制显示出治疗效果。通过使用 MSCs 作为载体细胞,中和抗体在与癌细胞反应之前解决了溶瘤病毒的清除主要问题。本研究的目的是表征感染呼肠孤病毒 3 型迪林(T3D)的 MSCs 对体外癌症治疗的影响。脂肪源性间充质干细胞(AD-MSCs)被感染呼肠孤病毒 T3D,并评估其生物学特性。然后,评估感染呼肠孤病毒的 AD-MSCs 对 TC-1 细胞细胞因子谱、一氧化氮(NO)产生和凋亡诱导的影响。我们的结果表明,AD-MSCs 的分化潜能受呼肠孤病毒影响。然而,感染后表型不受影响。然后,感染呼肠孤病毒的 AD-MSCs 在 TC-1 细胞中显示肿瘤坏死因子-α(TNF-α)和 NO 产生增加,转化生长因子-β1(TGF-β1)和白细胞介素-10(IL-10)减少。此外,与对照组相比,通过共培养 TC-1 细胞与感染 AD-MSCs,凋亡明显增加,并且实验组中同时激活了内源性和外源性凋亡途径。总之,数据表明,随着 TNF-α和 NO 产生的增加以及 IL-10 和 TGF-β产生的减少,AD-MSCs 可以增强呼肠孤病毒在癌细胞中的溶瘤作用。此外,结果表明 AD-MSCs 可以作为呼肠孤病毒 T3D 的有效载体细胞候选物,以最大限度地提高其抗癌细胞活性。

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