A Preview of Selected Articles

unwanted interactions between blood and the cell population employed can induce significant levels of clotting. Increased clotting has the potential to reduce the regenerative output of stem cell therapies, but more importantly, this process may also increase the risk of deleterious side effects. Both in vitro [1] and in vivo [2] assessments of interactions between human mesenchymal stem cells (MSCs) and blood have demonstrated that the expression of tissue factor (TF), a proclotting component, accelerates clot formation and reduces therapeutic efficacy, although we lack a fuller understanding of the clotting potential of other therapeutically relevant stem cell populations. Our first Featured Article from George et al. [3] now establishes that a wide range of stem cell types differentially promote clot formation via varying levels of TF expression, thereby advocating for the implementation of clotting activator analysis in safety assessments for stem cell therapies. In a Related Article, Gleeson et al. [4] demonstrate how the proclotting characteristics of MSCs can impede treatment of myocardial infarction (MI), but also describe how an anticlotting strategy can nullify these deleterious effects and promote regenerative function. The application of MSCs also extends to the treatment of multiple sclerosis (MS), a neurodegenerative disease of the central nervous system characterized by inflammatory demyelination and the development of severe neurological disability. The anti-inflammatory, immunomodulatory, and antioxidant activities of MSCs combined with their favorable safety profile have brought hope of an effective stem cell therapy for MS patients; however, we lack a full understanding of how MS and the associated proinflammatory environment affect MSC function. Unfortunately, very recent studies have provided evidence that MSCs derived from MS patients suffer from an early aging-like phenotype [5] with diminished paracrine neuroprotective abilities [6]. Our second Featured Article from Redondo et al. [7] describes how an increased susceptibility to nitrosative stress in combination with the reduced expression, activity, and secretion of antioxidants can contribute to the functional deficits observed in MSCs derived from MS patients. In a Related Article, Strong et al. [8] report that obesity imposes proinflammatory characteristics on adipose-derived stem cells (ASCs), impairs their ability to modulate the immune system, and negatively affects their therapeutic effect in MS patients.