Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran.
Int Immunopharmacol. 2024 Aug 20;137:112407. doi: 10.1016/j.intimp.2024.112407. Epub 2024 Jun 13.
Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. Broad-spectrum antibiotics are used to treat it. However, due to antibiotic resistance, alternative treatments are needed. Mesenchymal stem cells (MSCs) have become a promising therapeutic tool for sepsis due to their immunomodulatory properties. The limitations of MSC therapy have led to increased attention to cell derivatives such as conditioned medium (CM). This study investigates the immunomodulatory effects of young and old MSC-CM during the inflammatory phase of sepsis.
The cecal ligation and puncture (CLP) model was used to induce sepsis in mice. The mice were divided into four groups: sham, CLP, CLP treated with young MSC-CM, and CLP treated with old MSC-CM. The CM was injected intraperitoneally at 2-, 12-, and 24-hours post-surgery. After 72 h, blood was collected and white blood cells (WBCs) were counted. In addition, serum and tissue were isolated, and the levels of alanine transaminase (ALT) and aspartate transaminase (AST) in serum, bacterial load in the spleen, concentration of pro- and anti-inflammatory cytokines, and histopathology of liver and lung were investigated.
MSC-CM decreased serum AST and ALT levels, bacterial load in the spleen, and pro-inflammatory cytokines in serum. In addition, tissue damage was reduced, and the survival rate and WBC count increased. There was no significant difference between the young and old MSC-CM.
MSC-CM effectively reduced inflammation-induced tissue damage in the liver and lungs during sepsis. Although young MSC-CM had better immunomodulatory effects than old MSC-CM, the difference was not significant.
脓毒症是一种由感染引起的免疫反应失调导致的危及生命的疾病。广谱抗生素用于治疗它。然而,由于抗生素耐药性,需要替代治疗方法。间充质干细胞(MSCs)由于其免疫调节特性,已成为脓毒症治疗的有前途的治疗工具。MSC 治疗的局限性导致人们越来越关注细胞衍生物,如条件培养基(CM)。本研究探讨了年轻和老年 MSC-CM 在脓毒症炎症期的免疫调节作用。
使用盲肠结扎和穿刺(CLP)模型在小鼠中诱导脓毒症。将小鼠分为四组:假手术组、CLP 组、CLP 用年轻 MSC-CM 治疗组和 CLP 用老年 MSC-CM 治疗组。CM 在手术后 2、12 和 24 小时通过腹腔内注射。72 小时后,采集血液并计数白细胞(WBC)。此外,还分离血清和组织,检测血清中天冬氨酸转氨酶(ALT)和丙氨酸转氨酶(AST)水平、脾脏细菌负荷、促炎和抗炎细胞因子浓度以及肝和肺的组织病理学。
MSC-CM 降低了血清 AST 和 ALT 水平、脾脏细菌负荷和血清中促炎细胞因子。此外,还减少了组织损伤,提高了存活率和白细胞计数。年轻和老年 MSC-CM 之间没有显著差异。
MSC-CM 有效减轻了脓毒症期间肝脏和肺部炎症引起的组织损伤。虽然年轻 MSC-CM 比老年 MSC-CM 具有更好的免疫调节作用,但差异不显著。