A preview of selected articles

A wide range of experimental and clinical studies have underlined the immunomodulatory, anti-inflammatory, and wound healing capabilities of mesenchymal stem cells (MSCs), leading to their application in a range of reparative and regenerative approaches. However, these multifunctional cells also possess another less appreciated ability, with multiple in vitro studies providing evidence for the potent and direct bactericidal activity of MSCs. Given the unfortunate rise of antibioticresistant bacteria and the devastating effects observed following infections in debilitated patients, many have sought to explore cotreatment with MSCs as a means to potentiate conventional antibiotic therapy. Previous research efforts have demonstrated that MSCs directly influence the immunological properties of macrophages and neutrophils via secreted factors, while they also produce antimicrobial peptides that directly kill bacteria either by disrupting the integrity of the microbial membrane or by recruiting immune cells following the induced release of proinflammatory cytokines. Overall, the full delineation of the molecular mechanisms that underlie the antimicrobial activity of MSCs in vitro and in vivo may allow for the development of exciting new means to prevent devastating infections by antibiotic-resistant bacteria. In our first Featured Article from STEM CELLS Translational Medicine, Chow et al explore the mechanisms by which MSCs augment the antimicrobial activity of various classes of conventional antibiotics, including the generation of enhanced activity against drug-resistant strains of Staphylococcus aureus (S. aureus). In a Related Article published in STEM CELLS, Qian et al demonstrated that adipose-derived MSCs can attenuate S. aureus-induced lung injury and improve survival of infected mice by reducing the bacterial load and alleviating inflammatory responses through paracrine-acting secreted factors. Asthma, a chronic inflammatory disease characterized by CD4+ T helper 2 lymphocyte-controlled immune responses against allergens that result in lung remodeling, deregulated inflammation, airway hyperresponsiveness, and airflow obstruction, affects a significant and everrising number of people worldwide. The common house dust mite (HDM) represents the most common allergen implicated in human asthma, affecting approximately 85% of asthmatic patients globally. Conventional therapeutics efficiently relieve asthmatic symptoms in most patients; however, said approaches fail to reverse established lung remodeling and bring little relief to those cohorts of patients with more severe pathologies. As MSCs display pro-regenerative, immunomodulatory, and anti-inflammatory capabilities, they may serve as a potentially exciting treatment option for patients with severe asthma; however, important questions remain concerning the dosing regimens required to optimize therapeutic effects and the exact mechanisms involved in the anti-asthmatic response following MSC administration. In our second Featured Article from STEM CELLS Translational Medicine, Castro et al. report that while multiple doses of MSCs can reduce lung inflammation and remodeling and improve lung mechanics in a mouse model of allergic asthma, this approach also results in immunosuppressive side-effects. In a Related Article published in STEM CELLS, Braza et al demonstrated that lung macrophages phagocytose MSCs following administration to a mouse model of asthma, with macrophages then becoming polarized into an immunosuppressive phenotype to induce the anti-inflammatory effects observed.