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Producing an adequate number of muscle stem cells (MuSCs) with robust regenerative potential is essential for the successful cell therapy of muscle-wasting disorders. We have recently developed a method to produce skeletal myogenic cells with exceptional engraftability and expandability through an in vivo pluripotent stem cell (PSC) differentiation approach. We have subsequently mapped engraftment and gene expression and found that leukemia inhibitory factor receptor (Lifr) expression is positively correlated with engraftability. We therefore investigated the effect of LIF, the endogenous ligand of LIFR, on cultured MuSCs and examined their engraftment potential. We found that LIF-treated MuSCs exhibited elevated expression of PAX7, formed larger colonies from single cells, and favored the retention of PAX7+ “reserve cells” upon myogenic differentiation. This suggested that LIF promoted the maintenance of cultured MuSCs at a stem cell stage. Moreover, LIF enhanced the engraftment capability of MuSCs that had been expanded in vitro for 12 days by 5-fold and increased the number of MuSCs that repopulated the stem cell pool post-transplantation. These results thereby demonstrated the effectiveness of our in vivo PSC differentiation platform to identify positive regulators of the engraftability of cultured MuSCs.

BackgroundThe United States faces a nursing shortage driven by a burnout epidemic among nurses and nursing students. Nursing students are an integral population to fuel the nursing workforce at high risk of burnout and increased rates of perceived stress. ObjectiveThe aim of this paper is to describe WellNurse, a holistic, interdisciplinary, multidimensional longitudinal research study that examines evidence-based interventions intended to reduce burnout and increase resilience among graduate and undergraduate nursing students. MethodsGraduate and undergraduate nursing students matriculated at a large public university in the northeastern United States are eligible to enroll in this ongoing, longitudinal cohort study beginning in March 2021. Participants complete a battery of health measurements twice each semester during the fourth week and the week before final examinations. The measures include the Perceived Stress Scale, the Satisfaction with Life Scale, the Oldenburg Burnout Inventory, the Brief Resilience Scale, and the Pittsburgh Sleep Quality Index. Participants are eligible to enroll in a variety of interventions, including mindfulness-based stress reduction, mindful eating, fitness training, and massage therapy. Those who enroll in specific, targeted interventions complete additional measures designed to target the aim of the intervention. All participants receive a free Fitbit device. Additional environmental changes are being implemented to further promote a culture that supports academic well-being, including recruiting a diverse student population through evidence-based holistic admissions, inclusive teaching design, targeted resilience and stress reduction workshops, and cultural shifts within classrooms and curricula. The study design protocol is registered at Open Science Framework (DOI 10.17605/OSF.IO/NCBPE). ResultsThe project was funded on January 1, 2022. Data collection started in March 2022. A total of 267 participants have been recruited. Results will be published after each semester starting in December 2023. WellNurse evaluation follows the Rapid Cycle Quality Improvement framework to continuously monitor ongoing project processes, activity outcomes, and progress toward reducing burnout and increasing resilience. Rapid Cycle Quality Improvement promotes the ability to alter WellNurse interventions, examine multiple interventions, and test their effectiveness among the nursing education population to identify the most effective interventions. ConclusionsAcademic nursing organizations must address student burnout risk and increase resilience to produce a future workforce that provides high-quality patient care to a diverse population. Findings from WellNurse will support evidence-based implementations for public baccalaureate and master’s nursing programs in the United States. International Registered Report Identifier (IRRID)DERR1-10.2196/49020