Editors' ChoiceStem Cells

Antimicrobial Effects of Stem Cells

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Science Translational Medicine  16 Jan 2013:
Vol. 5, Issue 168, pp. 168ec13
DOI: 10.1126/scitranslmed.3005667

Although mesenchymal stem cells (MSCs) have shown therapeutic promise for a wide range of conditions, excitement over their therapeutic potential has been tempered in some settings by concerns that they may be immunosuppressive and thus increase susceptibility to serious infections. Immunosuppressive effects of MSCs would be of particular concern if MSCs were used to treat conditions such as severe sepsis or infection-related acute respiratory distress syndrome (ARDS), two conditions for which preclinical studies have suggested that MSCs may be beneficial. To address this concern, Lee and colleagues studied the effects of MSCs on lung injury, inflammation, and bacterial growth in an ex vivo perfused human lung model of infection-related ARDS.

The experimental model in this study consisted of human lungs that were rejected for organ transplantation and kept perfused and ventilated to mimic normal lung physiologic function. Lung injury was induced with direct intralobar instillation of live bacteria. One to two hours later, MSCs (or normal human lung fibroblasts as controls) were instilled in the same manner or intravenously. As in the authors’ prior work in noninfectious models, MSCs improved the ability of the alveolar epithelium (lining of the lung) to clear fluid and reduced the neutrophil count in the lung airspaces. Furthermore, MSCs decreased the bacterial counts in the lung airspaces in a dose-dependent manner. Interestingly, MSCs were more effective than were intravenous antibiotics in improving the function of the lung epithelium and reducing bacterial counts in the airspaces and in the fluid perfusing the lung. Many of these effects appeared to be mediated in part by the effects of keratinocyte growth factor (which was secreted by MSCs) on monocytes.

This paper uses a unique translational model to further allay concerns that MSCs may have untoward immunosuppressive effects when used to treat sequelae of severe infection. The direct comparison with antibiotic administration, always used clinically but less commonly used as an experimental control in lab-based studies, further enhances the clinical relevance, although how MSCs will compare with antibiotics in vivo in the setting of a functional immune system remains to be seen. Likewise, it remains unclear whether immunosuppressive effects of MSCs could enhance susceptibility to secondary infection, a common problem in hospitalized patients. Nevertheless, this study takes another step toward early-phase clinical trials of cell-based therapies for infectious and infection-related diseases, so that we may soon know whether the preclinical promise of MSC treatment has real clinical potential.

J. W. Lee et al., Therapeutic effects of human mesenchymal stem cells in ex vivo human lungs injured with live bacteria. Am. J. Respir. Crit. Care Med., published online 4 January 2013 (10.1164/rccm.201206-0990OC). [PubMed]

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