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

Mahtab  Tapak; Somaye  Sadeghi; Tooba  Ghazanfari; Nariman  Mosaffa; S. Zahra  Mirsanei; Seyed Mahmoud Masiha  Hashemi

doi:10.18502/ijaai.v23i5.16751

Mahtab Tapak Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Somaye Sadeghi Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
Tooba Ghazanfari Immunoregulation Research Center, Shahed University, Tehran, Iran
Nariman Mosaffa Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
S. Zahra Mirsanei Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Seyed Mahmoud Masiha Hashemi Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v23i5.16751

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

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 a 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 the 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.