The Effects of Mesenchymal Stem Cells Loaded with Oncolytic Coxsackievirus A21 on Mouse Models of Colorectal Cancer.

IF 2.3 4区 医学 Q3 ONCOLOGY
Reza Karbalaee, Saber Mehdizadeh, Hadi Esmaeili Gouvarchin Ghaleh, Morteza Izadi, Bahman Jalali Kondori, Ruhollah Dorostkar, Seyed Morteza Hosseini
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Abstract

Background: Cancer is a major cause of death worldwide. Colorectal cancer is the second most common type. Additional treatments like chemotherapy and radiation therapy may be recommended. Developing new techniques is vital due to drug resistance and a lack of targeted therapies.

Objective: In this study, the effects of mesenchymal stem cells (MSCs) loaded with oncolytic Coxsackievirus A21 (CVA21) on a mouse model of CRC were investigated.

Methods: The therapeutic potency of MSCs loaded with oncolytic CVA21 were evaluated in an experimental mouse model of colorectal cancer which received an injection CT26 cells per mouse subcutaneously. Splenocyte proliferation index, lactate dehydrogenase (LDH) assay, nitric oxide (NO) production assessment, and cytokine assay (IFN-γ, IL-4, IL-10, and TGF-β) in the splenocyte supernatant were all used to evaluate the impact of MSCs loaded with CVA21.

Results: The results of this study showed that the treatment of a mouse model of colorectal cancer with MSCs loaded with oncolytic CVA21 could significantly suppress the tumor growth, which was accompanied by stimulation of splenocytes proliferation index, an increase of NO and LDH. Also, MSCs loaded with oncolytic CVA21 increased the secretion of IFN-γ and decreased the secretion of IL-4, IL-10, and TGF-β.

Conclusion: The results of the current study suggest that MSCs loaded with oncolytic CVA21 therapy for the CRC mouse model may have some potential advantages. On the other hand, the results of the study showed that, in addition to activating the acquired immune system, the use of MSCs loaded with oncolytic CVA21 also stimulates the innate immune system by increasing level of nitric oxide.

间充质干细胞负载溶瘤柯萨奇病毒 A21 对结肠直肠癌小鼠模型的影响
背景:癌症是全球死亡的主要原因。大肠癌是第二大常见癌症。患者可能需要接受化疗和放疗等其他治疗。由于耐药性和靶向疗法的缺乏,开发新技术至关重要:本研究探讨了间充质干细胞(MSCs)负载溶瘤柯萨奇病毒 A21(CVA21)对小鼠 CRC 模型的影响:方法:在结直肠癌实验小鼠模型中,每只小鼠皮下注射CT26细胞,评估间充质干细胞负载溶瘤CVA21的治疗效力。脾细胞增殖指数、乳酸脱氢酶(LDH)检测、一氧化氮(NO)生成评估和脾细胞上清液中细胞因子(IFN-γ、IL-4、IL-10和TGF-β)检测均用于评估负载CVA21的间充质干细胞的影响:结果:研究结果表明,间充质干细胞负载溶瘤 CVA21 治疗小鼠结直肠癌模型可显著抑制肿瘤生长,同时刺激脾细胞增殖指数、NO 和 LDH 的增加。同时,间充质干细胞负载溶瘤 CVA21 增加了 IFN-γ 的分泌,减少了 IL-4、IL-10 和 TGF-β 的分泌:本研究结果表明,间充质干细胞负载溶瘤 CVA21 治疗 CRC 小鼠模型可能具有一些潜在的优势。另一方面,研究结果表明,除了激活获得性免疫系统外,使用含有溶瘤 CVA21 的间充质干细胞还能通过增加一氧化氮水平来刺激先天性免疫系统。
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来源期刊
Current cancer drug targets
Current cancer drug targets 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
105
审稿时长
1 months
期刊介绍: Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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