Engineered Cardiac Microtissue Biomanufacturing Using Human Induced Pluripotent Stem Cell Derived Epicardial Cells.

Epicardial cells are a crucial component in constructing in vitro 3D tissue models of the human heart, contributing to the ECM environment and the resident mesenchymal cell population. Studying the human epicardium and its development from the proepicardial organ is difficult, but induced pluripotent stem cells can provide a source of human epicardial cells for developmental modeling and for biomanufacturing heterotypic cardiac tissues. This study shows that a robust population of epicardial cells (approx. 87.7% WT1+) can be obtained by small molecule modulation of the Wnt signaling pathway. The population maintains WT1 expression and characteristic epithelial morphology over successive passaging, but increases in size and decreases in cell number, suggesting a limit to their expandability in vitro. Further, low passage number epicardial cells formed into more robust 3D microtissues compared to their higher passage counterparts, suggesting that the ideal time frame for use of these epicardial cells for tissue engineering and modeling purposes is early on in their differentiated state. Additionally, the differentiated epicardial cells displayed two distinct morphologic sub populations with a subset of larger, more migratory cells which led expansion of the epicardial cells across various extracellular matrix environments. When incorporated into a mixed 3D co-culture with cardiomyocytes, epicardial cells promoted greater remodeling and migration without impairing cardiomyocyte function. This study provides an important characterization of stem cell-derived epicardial cells, identifying key characteristics that influence their ability to fabricate consistent engineered cardiac tissues.

The effect of a workplace wellness program on disability, function and pain in healthcare providers workers with low back pain-outcomes of 3040 academic health center employees.

PURPOSE: (1) Identification of musculoskeletal risk factors for healthcare providers suffering low back pain (LBP) and the creation of risk profiles for those individuals and (2) analyze the impact of a workplace wellness program on healthcare providers who suffer from low back pain. METHODS: A total of 3040 employees at an academic healthcare center underwent a computer-adaptive survey of health-related quality of life (HRQOL), biometric tests, and a disability and functional movement assessment as part of the workplace wellness program (WWP). Clinical interventions with a rehabilitation specialist were offered to employees identified as at risk for low back pain. Data collected were analyzed using descriptive methods and multivariable regressions to address the study objectives. RESULTS: Of the 3040 healthcare providers enrolled in this study, 77% identified with non-specific LBP with greater weakness, numbness, reduced flexibility, and physical activity. The major predictive risk factors for LBP were Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference score, PROMIS fatigue, previous work injury, flexibility, numbness, PROMIS social function, level of education, and BMI. Healthcare providers with LBP who completed the WWP improved in most dimensions of HRQOL and disability and functional outcomes. CONCLUSIONS: A high proportion of healthcare providers suffer from LBP as a result of the nature of their work. Disability and functional outcomes measurements and PROMIS results quantitatively assess healthcare providers with LBP. Organizations can develop injury mitigation programs to target employees at high risk of LBP using the risk factors we identify. Completion of the WWP was associated with improvements in disability, HRQOL and functional measures.