CAJ | 학술논문

背景：骨髓间充质干细胞输注有望成为临床治疗炎症性肠病的新的有效生物治疗手段，但其肿瘤学安全性问题令人担忧，是决定间充质干细胞能否广泛用于炎症性肠病治疗的关键，亟待研究。目的：利用小鼠模型观察骨髓间充质干细胞输注对炎症性肠病结肠炎的疗效，并明确间充质干细胞对炎症性肠病炎症癌变的影响。方法：应用葡聚糖硫酸钠构建 Balb/c(H-2d)小鼠的实验性结肠炎模型，经尾静脉输注分离培养的同系基因型骨髓间充质干细胞，对比观察间充质干细胞的疗效并评价结肠炎的组织病理学改善情况；应用葡聚糖硫酸钠联合偶氮氧甲烷构建 Balb/c(H-2d)小鼠的结肠炎癌变模型，对比观察间充质干细胞输注后小鼠肠道肿瘤的形成情况。结果与结论：在葡聚糖硫酸钠结肠炎模型，骨髓间充质干细胞组在实验结束时体质量丧失、大便潜血较PBS组均有减轻；间充质干细胞组中结肠组织炎症损伤严重度评分更低，镜下小鼠远端结肠黏膜结构基本完整，有小范围上皮缺损或隐窝缺损，黏膜层和黏膜下层较多炎症细胞浸润，可见毛细血管和小血管增生；体内示踪可见输注的间充质干细胞向结肠炎症病灶处黏膜下层归巢定殖。在葡聚糖硫酸钠/偶氮氧甲烷结肠炎癌变模型，间充质干细胞组小鼠肠道肿瘤数量及肿瘤负荷均明显小于对照组。结果提示输注骨髓间充质干细胞能明显改善炎症性肠病小鼠的结肠炎症病变，并抑制结肠炎向肿瘤的恶性转化，为间充质干细胞治疗炎症性肠病的生物安全性提供了客观的理论依据。
배경：골수간충질간세포수주유망성위림상치료염증성장병적신적유효생물치료수단，단기종류학안전성문제령인담우，시결정간충질간세포능부엄범용우염증성장병치료적관건，극대연구。목적：이용소서모형관찰골수간충질간세포수주대염증성장병결장염적료효，병명학간충질간세포대염증성장병염증암변적영향。방법：응용포취당류산납구건 Balb/c(H-2d)소서적실험성결장염모형，경미정맥수주분리배양적동계기인형골수간충질간세포，대비관찰간충질간세포적료효병평개결장염적조직병이학개선정황；응용포취당류산납연합우담양갑완구건 Balb/c(H-2d)소서적결장염암변모형，대비관찰간충질간세포수주후소서장도종류적형성정황。결과여결론：재포취당류산납결장염모형，골수간충질간세포조재실험결속시체질량상실、대편잠혈교PBS조균유감경；간충질간세포조중결장조직염증손상엄중도평분경저，경하소서원단결장점막결구기본완정，유소범위상피결손혹은와결손，점막층화점막하층교다염증세포침윤，가견모세혈관화소혈관증생；체내시종가견수주적간충질간세포향결장염증병조처점막하층귀소정식。재포취당류산납/우담양갑완결장염암변모형，간충질간세포조소서장도종류수량급종류부하균명현소우대조조。결과제시수주골수간충질간세포능명현개선염증성장병소서적결장염증병변，병억제결장염향종류적악성전화，위간충질간세포치료염증성장병적생물안전성제공료객관적이론의거。
BACKGROUND:Transfusion of bone marrow mesenchymal stem cells may become a novel and effective biological therapy for inflammatory bowel disease in clinical practice. Nevertheless, the oncological safety of the treatment is worrisome, and is a key to determine whether mesenchymal stem cells can be widely used in treatment of inflammatory bowel disease, and deserves further investigation. OBJECTIVE:To evaluate the therapeutic effect of bone marrow mesenchymal stem celltransfusion against inflammatory bowel disease in mouse models, and to clarify the effects of mesenchymal stem cells on tumorigenesis of inflammatory bowel disease. METHODS:Mouse model of colitis was established using Balb/c (H-2d) mice exposed to dextran sulfate sodium. Syngeneic bone marrow mesenchymal stem cells were transfused into mouse model through caudal vein. The therapeutic effect of mesenchymal stem cells was compared and observed, and pathological remission of colitis was evaluated. Mouse model of colitis-driven colon carcinogenesis was established using Balb/c (H-2d) mice exposed to dextran sulfate sodium and azoxymethane. Tumor formation within the murine colon was compared and observed after transfusion of mesenchymal stem cells. RESULTS AND CONCLUSION:In models of dextran sulfate sodium-induced colitis, weight loss and fecal occult blood were lessened in the bone marrow mesenchymal stem cellgroup compared with the phosphate buffered saline group. Histological damage score of colitis was less in the bone marrow mesenchymal stem cellgroup:mucosal structure of distal colon was almost intact under microscope, and there was smal area of epithelial defects and cryptal defects. Inflammatory cellinfiltration, proliferation of capil ary and smal vessels could be observed in mucosa and submucosa. Homing and colonization of mesenchymal stem cells in submucosa of inflamed colon could also be observed by in vivo tracing. In the dextran sulfate sodium/azoxymethane model of colitis-driven colon carcinogenesis, the number of intestinal tumors and tumor load were obviously less in the bone marrow mesenchymal stem cellgroup than in the control group. Results indicated that transfusion of bone marrow mesenchymal stem cells can apparently improve colitis lesions of mice with inflammatory bowel disease and inhibit carcinogenesis of colitis, which may provide theoretical support for the biological safety of mesenchymal stem cells transplantation for inflammatory bowel disease.