Mesenchymal Stem Cell Therapy Mitigates Acute and Chronic Lung Damages of Sulfur Mustard Analog Exposure

Iran J Allergy Asthma Immunol. 2024 Oct 6;23(5):563-577. doi: 10.18502/ijaai.v23i5.16751.

Abstract

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.

Keywords: Bronchoalveolar lavage fluid; Conditioned medium; Mesenchymal stem cell; Peritoneal macrophage; Sulfur mustard.

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / pathology
  • Acute Lung Injury / therapy
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Chemical Warfare Agents / toxicity
  • Chronic Disease
  • Cytokines / metabolism
  • Disease Models, Animal*
  • Lung / drug effects
  • Lung / pathology
  • Male
  • Mesenchymal Stem Cell Transplantation* / methods
  • Mesenchymal Stem Cells*
  • Mice
  • Mustard Gas* / analogs & derivatives
  • Mustard Gas* / toxicity

Substances

  • Mustard Gas
  • Cytokines
  • 2-chloroethyl ethyl sulfide
  • Chemical Warfare Agents