A Preview of Selected Articles

The term extracellular vesicles (EVs) describes 30–1,000 nm-sized lipid bilayer-delimited particles containing multiple proteins, RNAs, lipids, and metabolites that have been identified in various biological fluids [1, 2]. Evidence suggests that most, if not all, cells actively shed EVs for purposes including intercellular communication; however, recent studies have also highlighted their potential therapeutic value. The proposed therapeutic application of EVs stems both from the wish to avoid problems related to transplanting cells themselves, including the massive loss of transplanted cells, risk of malignant transformation, and immune rejection, and the simple, stable, and controllable nature of EVs that encourages large scale clinical manufacture [3]. Additionally, studies have established the therapeutic relevance of stem cell-EVs, with, for example, mesenchymal stem cell (MSC)-EVs able to pass through the mouse blood–brain barrier following intranasal administration to prevent abnormal neurogenesis and memory dysfunction [4] and neuroinflammation and cognitive impairments [5] in mouse models of brain disorders or following brain damage, respectively. Studies such as these provide evidence that stem cell-EV therapy may represent a potentially safe and efficient cell-free approach to the treatment of a wide range of conditions. In our First Featured Article from Stem Cells Translational Medicine, Narbute et al. report that the intranasal administration of EVs from stem cells derived from the dental pulp of human exfoliated deciduous teeth (SHEDs) can suppress disease symptoms in a rat model of Parkinson’s disease [6]. In a Related Article from Stem Cells, Schoefinius et al. establish that mouse bone marrow-derived MSC-EVs can target hematopoietic, long-term repopulating stem cells to rescue them from radiation-induced damage associated with the conditioning of patients before hematopoietic stem cell transplantation [7]. The corneal epithelium protects the eye, plays an essential role in preserving corneal clarity, and undergoes a highly coordinated stem cell-mediated regeneration process in response to severe injury or disease. However, this endogenous response does not suffice when faced with certain pathologic, highly inflammatory conditions that put the entire ocular surface at risk for permanent scarring and visual loss. The loss of or damage to the resident corneal epithelial stem/progenitor cells [8, 9] can significantly contribute to these outcomes. The management of corneal wounds consists mainly of supportive measures, including sutured lid closure or amniotic membrane grafting [10], although stem cell-based treatments are currently under assessment. A deeper understanding of the mechanisms that control corneal epithelial stem/progenitor cells under normal and pathogenic conditions may also shed light on the mechanisms underlying corneal physiology and contribute to the development of novel therapeutic strategies to restore vision. In our second Featured Article from Stem Cells Translational Medicine, Fernandes-Cunha et al. demonstrate how the reconstitution of the lyophilized MSC secretome within a viscoelastic gel can enhance corneal epithelial wound healing and mitigate the development of stromal scarring and neovascularization after corneal damage [11]. In a Related Article from Stem Cells, Bhattacharya et al. report that SOX2 regulates and interacts with P63 to control the corneal epithelial stem/progenitor cell state and that downregulation of SOX2/P63 by miR-450b induces cell differentiation, findings that may provide new targets for novel therapeutic approaches [12].