A preview of selected articles

Chronic obstructive pulmonary disease (COPD), one of the most significant causes of morbidity and mortality across the globe, refers to a group of diseases characterized by obstruction to the airway, inflammation, and lung damage. Severely affected COPD patients can face problems with everyday activities, including simple tasks such as walking or dressing. Tobacco smoking represents the primary causative factor in COPD, with additional risk factors including indoor/outdoor pollution and genetics. While removal of the risk factor (if possible) and the administration of current gold-standard treatment approaches can ameliorate certain aspects of the disease, the persistence of associated chronic inflammation and oxidative stress has driven the development of novel anti-inflammatory/immunomodulatory strategies, including the administration of mesenchymal stem cells (MSCs). Initial preclinical studies have provided evidence that MSCs can alleviate inflammation and reduce emphysema (the progressive loss of functional parenchymal lung tissue and alveolar gas exchange area) following either systemic or intratracheal administration; however, MSC therapy in human COPD patients has so-far failed to induce significant clinical improvements, even though results suggest that this therapeutic strategy does alter systemic inflammation. These findings provide support for ongoing research into the consequences of MSC therapy and the molecular events underpinning COPD development, with the final aim of developing novel therapeutic strategies and improving patient outcomes. In the first of our Featured Articles published this month in STEM CELLS Translational Medicine, Armitage et al describe how phase I clinical study results support the use of MSC therapy to modulate pathological inflammatory pathways in patients suffering from chronic airway diseases such as COPD. In a Related Article published recently in STEM CELLS, Hu et al investigated the role of Wnt/β-catenin signaling in epithelial progenitor cells during lung organoid formation and demonstrated the impaired function of progenitors in a mouse model of COPD. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptor proteins that function as transcription factors to regulate metabolic control and, in particular, whole-body lipid homeostasis. The three different PPAR isoforms (PPARα, PPARβ/δ, and PPARγ) become activated by the binding of various endogenous metabolic ligands, display different tissue expression patterns, and induce differing downstream effects. PPAR functions include the regulation of the oxidative breakdown of fats (PPARα and PPARδ) and fat cell differentiation and lipid storage (PPARγ), with additional roles including cholesterol flux regulation (PPARγ and PPARδ). Importantly, the PPARs also represent therapeutic targets for conditions such as diabetes, cancer, atherosclerosis, inflammation, and hypertension while also playing critical roles in immune responses. Interestingly, the modulation of PPAR function in various stem cell populations has the potential to significantly improve their associated therapeutic output; for example, Luz-Crawford et al demonstrated that PPARδ inhibition improved the immunosuppressive/anti-inflammatory function of MSCs after administration in a mouse model of arthritis; however, the role of PPARδ in human MSCs and related cell types remains uncertain. Meanwhile, a study by Guo et al reported that PPARγ inhibition improved the expansion of rare hematopoietic stem and progenitor cells (HSPCs) isolated from human cord blood by enhancing glycolysis, thereby increasing the relevance of cord blood to hematopoietic cell transplantation. In the second of our Featured Articles published this month in STEM CELLS Translational Medicine, Carty et al report that the inhibition of PPARδ enhances the efficacy of human multipotent adult progenitor cells (MAPCs) in a preclinical model of acute graft vs host disease (GvHD). In a Related Article published recently in STEM CELLS, Ma et al demonstrated the importance of PPARγ in supporting the function of transcriptional repressor Hes1 (hes family bHLH transcription factor 1) during stress hematopoiesis.