Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran AND Department of Laboratory, Alinasab Hospital, Iranian Social Security Organization (ISSO), Tehran, Iran.
Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
Iran J Allergy Asthma Immunol. 2024 Oct 6;23(5):563-577. doi: 10.18502/ijaai.v23i5.16751.
Sulfur mustard (SM) is an established chemical weapon that can result in severe damage to parts of the body. Currently, there are no effective treatments available for SM-caused damage. We aimed to investigate the therapeutic potential of adipose-derived mesenchymal stromal cells (AD-MSCs) and conditioned medium (CM-MSCs) in acute and chronic pulmonary mouse models caused by 2-chloroethyl ethyl sulfide (CEES), an SM analog. The mice were divided into 4 experimental groups:(1) CEES+AD-MSCs, (2) CEES+CM-MSCs, (3) CEES, and (4) control. The model observation time was divided into 7 days for the short and 6 months for the long term. AD-MSCs were injected into mice via intraperitoneal injection 24 hours after CEES exposure. The therapeutic effects of AD-MSCs on pulmonary tissue damage were assessed using histopathologic assay, measuring the neutrophil count, and bronchial alveolar lavage fluid (BALF) protein level. The levels of inflammatory and anti-inflammatory cytokines were evaluated using the enzyme-linked immunosorbent assay as the outcomes of interest. Lung damage progression was reduced by AD-MSC treatment in mice after CEES injection into the peritoneum. The proportion of CD11b+F4/80+ macrophages in peritoneum was significantly lowered by AD-MSC treatment following CEES exposure. AD-MSC administration also reduced the level of pro-inflammatory cytokines, BALF protein, and nitric oxide levels in the peritoneal cavity. By reducing inflammation and enhancing tissue healing, AD-MSCs and CM-MSC help prevent acute lung damage caused by CEES. The current study supports the use of a mouse model as a solid experimental foundation and indicates potential use for future cell treatment.
芥子气（SM）是一种已确立的化学武器，可对身体部位造成严重损害。目前，尚无针对 SM 损伤的有效治疗方法。我们旨在研究脂肪间充质基质细胞（AD-MSCs）和条件培养基（CM-MSCs）在 2-氯乙基乙基硫醚（CEES）引起的急性和慢性肺小鼠模型中的治疗潜力，CEES 是 SM 的类似物。将小鼠分为 4 个实验组：（1）CEES+AD-MSCs，（2）CEES+CM-MSCs，（3）CEES 和（4）对照。模型观察时间分为 7 天的短期和 6 个月的长期。CEES 暴露后 24 小时通过腹腔注射向小鼠注射 AD-MSCs。通过组织病理学检测、测量中性粒细胞计数和支气管肺泡灌洗液（BALF）蛋白水平，评估 AD-MSCs 对肺组织损伤的治疗作用。使用酶联免疫吸附试验评估炎症和抗炎细胞因子的水平作为感兴趣的结果。AD-MSC 治疗可减轻 CEES 注入腹膜后小鼠的肺损伤进展。与 CEES 暴露后接受 AD-MSC 治疗的小鼠相比，腹膜中 CD11b+F4/80+巨噬细胞的比例明显降低。AD-MSC 给药还降低了腹腔内促炎细胞因子、BALF 蛋白和一氧化氮水平。AD-MSCs 和 CM-MSCs 通过减轻炎症和增强组织愈合，有助于预防 CEES 引起的急性肺损伤。本研究支持使用小鼠模型作为坚实的实验基础，并表明未来细胞治疗的潜在用途。
