[关键词]
[摘要]
目的:探讨间充质干细胞来源的外泌体(MSC-Exo)对人结肠癌CT26 细胞体外增殖、迁移的影响及对放射性肠炎(RE)荷瘤小鼠模型的治疗效果及其安全性。方法:利用商品化含MSC-Exo 的液体敷料产品(MSC-Exo 产品),通过纳米颗粒追踪分析、透射电镜、WB法对其中的MSC-Exo 进行鉴定。采用CCK-8法和Transwell 小室法检测MSC-Exo 产品对结肠癌CT26 细胞增殖、迁移的影响。构建CT26细胞荷瘤小鼠模型,连续7 d分别给予400 μL MSC-Exo 产品、MSC培养基或生理盐水灌胃,评估MSC-Exo 产品在体内对肿瘤生长和小鼠生存的影响。构建RE荷瘤小鼠模型,连续7 d分别给予400 μL MSC-Exo 产品、MSC培养基、生理盐水灌胃治疗,通过小肠组织H-E 染色法评估MSC-Exo 产品治疗RE的有效性与安全性。结果:纳米颗粒追踪分析、透射电镜、WB法的鉴定结果确证了商品化的液体敷料中含有MSC-Exo 有效成分。体外研究表明,MSC-Exo 产品成分不会促进结肠癌CT26细胞的增殖和迁移,具有安全性。体内研究结果发现,MSC-Exo 产品的灌胃给药并不影响荷瘤小鼠的肿瘤生长和生存期,但RE荷瘤小鼠模型接受MSC-Exo 产品灌胃治疗后,荷瘤小鼠血便、黏液便症状得到缓解,H-E染色结果显示小鼠肠壁组织的组织形态完整性相较于对照组有所改善,提示MSC-Exo 产品对荷瘤小鼠的RE具有疗效,并且在致瘤性及肿瘤转移方面具有安全性。结论:商品化含MSC-Exo的液体敷料并不促进体外结肠癌细胞的增殖、迁移,对CT26细胞荷瘤小鼠肿瘤生长和生存期无明显影响,但对荷瘤小鼠模型的RE具有治疗作用,改善了肠道组织的损伤。
[Key word]
[Abstract]
Objective: To explore the effects of mesenchymal stem cell-derived exosomes (MSC-Exo) on the in vitro proliferation and migration of human colorectal cancer cells (CT26), and assess the effects and safety of MSC-Exo treatment for tumor-bearing mouse model with radiation enteritis (RE). Methods: Commercially available liquid dressing products containing MSC-Exo (MSC-Exo product) were utilized for this study. Exosome components were identified through Nanoparticle Tracking Analysis (NTA), transmission electron microscopy (TEM), and WB analysis. The effects of MSC-Exo product on CT26 cell proliferation and migration were detected using the CCK-8 and Transwell assays. A CT26 tumor-bearing mouse model was established, and the mice were intragastrically administered with 400 μL MSC-Exo product, MSC culture medium, or saline for 7 consecutive days to evaluate the effects of MSC-Exo product on tumor growth and mouse survival in vivo. A radiation enteritis tumor-bearing mouse model was also established, and administered similar treatments. The efficacy and safety of MSC-Exo product treatment for RE were evaluated through H-E staining of small intestine tissues. Results: NTA, TEM, and WB analyses confirmed the presence of MSC-Exo in the commercial liquid dressing products. In vitro studies showed that MSC-Exo product did not promote tumor proliferation or migration. In vitro studies revealed that MSC-Exo product did not promote the proliferation and migration of colon cancer CT26 cells and was thus safe. In vivo studies revealed that gavage administration of MSC-Exo product did not affect tumor growth and the survival period of tumor-bearing mice. However, after treating radiation enteritis tumor-bearing mouse model with MSC-Exo product via gavage, the symptoms of bloody and mucous stool were relieved. H-E staining results demonstrated improved tissue morphology integrity in the intestinal tissues of the mice compared with that of the mice in the control group, suggesting that MSC-Exo product was effective in treating RE in tumor-bearing mice and was safe in terms of oncogenicity and tumor metastasis. Conclusion: Commercial liquid dressing products containing MSC-Exo do not promote the proliferation and migration of colon cancer cells in vitro, and have no obvious effects on tumor growth and survival period of CT26 cell tumor-bearing mice, but are effective in treating RE in the tumor-bearing mouse model and improve intestinal tissue damage.
[中图分类号]
[基金项目]
国家自然科学基金项目(No. 82071796)