Mesenchymal Stem Cell Therapy Mitigates Acute and Chronic Lung Damages of Sulfur Mustard Analog Exposure
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Published on: April 30, 2019
Mahtab Tapak1, Somaye Sadeghi2, Tooba Ghazanfari3
1Department 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. mahtabtapak@sbmu.ac.ir.
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.
Insights
Adipose-derived mesenchymal stromal cells (AD-MSCs) show therapeutic potential against lung damage caused by sulfur mustard (SM) analogs. This study demonstrates AD-MSCs reduce inflammation and improve tissue healing in mouse models, offering a promising avenue for future treatments.
Area of Science:
- Toxicology
- Regenerative Medicine
- Immunology
Background:
- Sulfur mustard (SM) is a chemical warfare agent causing severe tissue damage with no current effective treatments.
- Adipose-derived mesenchymal stromal cells (AD-MSCs) and their conditioned medium (CM-MSCs) are being explored for therapeutic applications.
- Developing effective treatments for SM-induced injuries remains a critical unmet medical need.
Purpose of the Study:
- To investigate the therapeutic efficacy of AD-MSCs and CM-MSCs in mitigating acute and chronic pulmonary damage induced by 2-chloroethyl ethyl sulfide (CEES), an SM analog.
- To evaluate the impact of AD-MSC treatment on inflammatory responses and tissue repair mechanisms in a mouse model.
- To establish a robust mouse model for assessing potential cell-based therapies for chemical weapon injuries.
Main Methods:
- Establishment of acute (7-day) and chronic (6-month) pulmonary mouse models using CEES exposure.
- Intraperitoneal administration of AD-MSCs or CM-MSCs 24 hours post-CEES exposure.
- Assessment of therapeutic effects via histopathology, neutrophil counts, bronchoalveolar lavage fluid (BALF) protein levels, cytokine analysis (ELISA), and macrophage profiling (CD11b+F4/80+).
Main Results:
- AD-MSC treatment significantly reduced lung damage progression following CEES exposure.
- A notable decrease in peritoneal CD11b+F4/80+ macrophages was observed after AD-MSC administration.
- AD-MSC therapy led to reduced levels of pro-inflammatory cytokines, BALF protein, and nitric oxide in the peritoneal cavity.
Conclusions:
- AD-MSCs and CM-MSCs demonstrate significant potential in preventing and treating acute lung damage caused by CEES exposure.
- The observed reduction in inflammation and enhancement of tissue healing by AD-MSCs supports their therapeutic utility.
- This study provides a strong experimental foundation for the future clinical application of cell-based therapies against sulfur mustard-induced injuries.
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