Chemical warfare agent and biological toxin-induced pulmonary toxicity: Could stem cells provide potential therapies?

US Army, Research, Development and Engineering Command, Edgewood Chemical Biological Center , Aberdeen Proving Ground, MD , USA.
Inhalation Toxicology (Impact Factor: 2.26). 01/2013; 25(1):37-62. DOI: 10.3109/08958378.2012.750406
Source: PubMed


Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

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    • "For instance, stem cells administered as an aerosol have been demonstrated to be successfully used in healing skin burns and scars (Gravante et al. 2007, Gerlach et al, 2011). Great expectations are related to the regenerative medicine of the lungs -the vital organ which can be easily damaged due to inhalation of hot or aggressive gases and vapours (Angelini et al, 2013). The natural way of delivery of therapeutic agents to the lungs is their conversion to aerosol which may be naturally inhaled and deposited inside the respiratory system. "
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    ABSTRACT: Aerosols are conveniently used for delivery of medicines to the human body. The most common application is inhalation of anti-asthmatic or anti-inflammatory drugs, nevertheless the spectrum of therapeutic agents that may be administered via the respiratory system is continuously expanding. Aerosols are also used topically (on skin) as a method of speeding up the healing. In this context, biocolloids (e.g., cell suspensions) are considered as the material for which the proper atomization method must be established to assure that local hydrodynamic stresses related to droplet formation will not destroy the living cells. In this work we test the influence of selected spraying techniques on the integrity and survival of different types of cells after the atomization process using medical atomizers. Medical nebulizers and spray devices were characterized in respect of emitted droplet size distribution and used to aerosolize model bio-colloids (suspensions of yeast, bacteria and mouse fibroblasts). Cell viability after spraying was determined via direct microscopic observations and specific microbiological assays. Commonly used medical inhalers produce droplets which are too small (Dv50 ≈ 4-5.5 μm) to contain whole living cells. As generation of such fine droplets is related to high local hydrodynamic stresses, cell viability in the suspension is strongly reduced even for small and mechanically resistant cells. Nasal atomizer (spray pump) and mechnical Microsprayer produce larger droplets (Dv50 ≈ 50-80 μm) which are capable of carrying intact fibroblast cells. Due to a lower shear during atomization process in these devices, the cells remain viable and active. Based on the results of experimental study, only selected techniques can be proposed for bio-colloid atomization in medical applications. Copyright © 2013, AIDIC Servizi S.r.l.
    06/2013; 32:2257-2262. DOI:10.3303/CET1332377