Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China.
Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China.
Stem Cell Res Ther. 2021 Mar 6;12(1):164. doi: 10.1186/s13287-021-02218-8.
Mesenchymal stem cells (MSCs) are derived from multiple tissues, including amniotic fluid (AF-MSCs) and the umbilical cord (UC-MSCs). Although the therapeutic effect of MSCs on sepsis is already known, researchers have not determined whether the cells from different sources require different therapeutic schedules or exert different curative effects. We assessed the biofunction of the administration of AF-MSCs and UC-MSCs in rats with caecal ligation and puncture (CLP)-induced sepsis.
CLP was used to establish a disease model of sepsis in rats, and intravenous tail vein administration of AF-MSCs and UC-MSCs was performed to treat sepsis at 6 h after CLP. Two phases of animal experiments were implemented using MSCs harvested in saline with or without filtration. The curative effect was measured by determining the survival rate. Further effects were assessed by measuring proinflammatory cytokine levels, the plasma coagulation index, tissue histology and the pathology of the lung, liver and kidney.
We generated rats with medium-grade sepsis with a 30-40% survival rate to study the curative effects of AF-MSCs and UC-MSCs. MSCs reversed CLP-induced changes in proinflammatory cytokine levels and coagulation activation. MSCs ameliorated CLP-induced histological and pathological changes in the lung, liver and kidney. AF-MSCs and UC-MSCs functioned differently in different tissues; UC-MSCs performed well in reducing the upregulation of inflammatory cytokine levels in the lungs and inhibiting the inflammatory cell infiltration into the liver capsule, while AF-MSCs performed well in inhibiting cell death in the kidneys and reducing the plasma blood urea nitrogen (BUN) level, an indicator of renal function.
Our studies suggest the safety and efficacy of AF-MSCs and UC-MSCs in the treatment of CLP-induced sepsis in rats and show that the cells potentially exert different curative effects on the main sepsis-affected tissues.
间充质干细胞(MSCs)来源于多种组织,包括羊水(AF-MSCs)和脐带(UC-MSCs)。尽管已经知道 MSCs 对脓毒症的治疗效果,但研究人员尚未确定来自不同来源的细胞是否需要不同的治疗方案或产生不同的疗效。我们评估了 AF-MSCs 和 UC-MSCs 在盲肠结扎和穿刺(CLP)诱导的脓毒症大鼠中的给药生物功能。
CLP 用于建立大鼠脓毒症疾病模型,并在 CLP 后 6 小时通过静脉尾静脉给予 AF-MSCs 和 UC-MSCs 来治疗脓毒症。使用生理盐水采集 MSC 并进行或不进行过滤,分两个阶段进行动物实验。通过测定存活率来衡量疗效。通过测定促炎细胞因子水平、血浆凝血指数、组织学和肺、肝、肾的病理学来评估进一步的效果。
我们生成了中等程度脓毒症的大鼠,存活率为 30-40%,以研究 AF-MSCs 和 UC-MSCs 的疗效。MSCs 逆转了 CLP 诱导的促炎细胞因子水平和凝血激活的变化。MSCs 改善了 CLP 诱导的肺、肝和肾组织学和病理学变化。AF-MSCs 和 UC-MSCs 在不同组织中的作用不同;UC-MSCs 在降低肺部炎症细胞因子水平上调和抑制肝包膜炎症细胞浸润方面表现良好,而 AF-MSCs 在抑制肾脏细胞死亡和降低肾功能指标血浆血尿素氮(BUN)水平方面表现良好。
我们的研究表明 AF-MSCs 和 UC-MSCs 在治疗 CLP 诱导的大鼠脓毒症中的安全性和有效性,并表明细胞对主要受脓毒症影响的组织可能具有不同的疗效。