Kheradmand Fatemeh, Yasaman Rahimzadeh Seyedeh Fatemeh, Esmaeili Seyed-Alireza, Negah Sajad Sahab, Farkhad Najmeh Kaffash, Nazari Seyedeh Elnaz, Hajinejad Mehrdad, Khodadoust Mohammad Ali, Fadaee Afsane, Afshari Jalil Tavakol, Khazaei Majid
Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Stem Cell Res Ther. 2025 Jan 7;16(1):5. doi: 10.1186/s13287-024-04062-y.
Inflammatory bowel disease (IBD) is a persistent inflammation of the digestive system, and Mesenchymal Stem Cells (MSCs) and their exosomes have demonstrated potential as treatments for this condition. The objective of this research was to examine the possible effectiveness of intraperitoneal injection of umbilical cord-MSCs (UC-MSCs) and their exosomes through a two-time injection regimen in a mouse model.
In this study, an animal model of a specific type of IBD in C57BL/6 mice, induced by dextran sulfate sodium (DSS), was utilized. The mice were treated with MSCs, exosomes, Mesalazine, and a combination of them. Upon sacrificing the mice, colon and spleen tissues were isolated to assess the changes in the mice's weight, colon length, spleen weight, and colitis' pathological symptoms. IL-10 and IL-17 levels were measured, and Treg and Th17 cell percentages were determined as well. Furthermore, colon tissue was stained to investigate histopathological changes.
In the groups that received MSCs, there was a significant reduction in the disease activity index and their combinations with exosomes and Mesalazine compared to the colitis group. Colon length increased in all groups except the exosome group. Histological measures were notably reduced in the MSC groups and their combinations. Significant increases in the IL-10 level of colon tissue and the proportion of Treg present in the spleen were observed in the groups receiving MSC and combination treatment. Furthermore, these groups showed a notable reduction in the percentage of spleen Th17 cells. However, IL17A decreased non-significantly in all groups.
The results showed that intraperitoneal injection of UC-MSCs and their combination with exosome and Mesalazine in a murine colitis model improved the disease's symptoms. Therefore, MSCs and their combination with exosomes can be a promising therapeutic approach along with other common drugs for IBD, but exosomes alone could not significantly reduce the symptoms of colitis.
炎症性肠病(IBD)是消化系统的一种持续性炎症,间充质干细胞(MSCs)及其外泌体已显示出作为该病症治疗方法的潜力。本研究的目的是通过在小鼠模型中进行两次注射方案,研究腹腔注射脐带间充质干细胞(UC-MSCs)及其外泌体的可能有效性。
在本研究中,利用硫酸葡聚糖钠(DSS)诱导的C57BL/6小鼠特定类型IBD的动物模型。用间充质干细胞、外泌体、美沙拉嗪及其组合对小鼠进行治疗。在处死小鼠后,分离结肠和脾脏组织以评估小鼠体重、结肠长度、脾脏重量和结肠炎病理症状的变化。测量白细胞介素-10(IL-10)和白细胞介素-17(IL-17)水平,并确定调节性T细胞(Treg)和辅助性T细胞17(Th17)的百分比。此外,对结肠组织进行染色以研究组织病理学变化。
与结肠炎组相比,接受间充质干细胞治疗的组及其与外泌体和美沙拉嗪的组合,疾病活动指数显著降低。除了外泌体组外,所有组的结肠长度均增加。间充质干细胞组及其组合的组织学指标显著降低。在接受间充质干细胞和联合治疗的组中,观察到结肠组织中IL-10水平和脾脏中Treg比例显著增加。此外,这些组的脾脏Th17细胞百分比显著降低。然而,所有组中IL17A的降低均无统计学意义。
结果表明,在小鼠结肠炎模型中腹腔注射脐带间充质干细胞及其与外泌体和美沙拉嗪的组合可改善疾病症状。因此,间充质干细胞及其与外泌体的组合与其他常用药物一起可能是治疗炎症性肠病的一种有前景的治疗方法,但单独使用外泌体不能显著减轻结肠炎症状。