The Extracellular Matrix Environment of Clear Cell Renal Cell Carcinoma Determines Cancer Associated Fibroblast Growth

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and is often caused by mutations in the oxygen-sensing machinery of kidney epithelial cells. Due to its pseudo-hypoxic state, ccRCC recruits extensive vasculature and other stromal components. Conventional cell culture methods provide poor representation of stromal cell types in primary cultures of ccRCC, and we hypothesized that mimicking the extracellular environment of the tumor would promote growth of both tumor and stromal cells. We employed proteomics to identify the components of ccRCC extracellular matrix (ECM) and found that in contrast to healthy kidney cortex, laminin, collagen IV, and entactin/nidogen are minor contributors. Instead, the ccRCC ECM is composed largely of collagen VI, fibronectin, and tenascin C. Analysis of single cell expression data indicates that cancer-associated fibroblasts are a major source of tumor ECM production. Tumor cells as well as stromal cells bind efficiently to a nine-component ECM blend characteristic of ccRCC. Primary patient-derived tumor cells bind the nine-component blend efficiently, allowing to us to establish mixed primary cultures of tumor cells and stromal cells. These miniature patient-specific replicas are conducive to microscopy and can be used to analyze interactions between cells in a model tumor microenvironment

Prevalence, risk factors, and cardiovascular disease outcomes associated with persistent blood pressure control: The Jackson Heart Study.

BackgroundMaintaining blood pressure (BP) control over time may contribute to lower risk for cardiovascular disease (CVD) among individuals who are taking antihypertensive medication.MethodsThe Jackson Heart Study (JHS) enrolled 5,306 African-American adults ≥21 years of age and was used to determine the proportion of African Americans that maintain persistent BP control, identify factors associated with persistent BP control, and determine the association of persistent BP control with CVD events. This analysis included 1,604 participants who were taking antihypertensive medication at Visit 1 and had BP data at Visits 1 (2000-2004), 2 (2005-2008), and 3 (2009-2013). Persistent BP control was defined as systolic BP ResultsAt Visit 1, 1,226 of 1,604 participants (76.4%) with hypertension had controlled BP. Overall, 48.9% of participants taking antihypertensive medication at Visit 1 had persistent BP control. After multivariable adjustment for demographic, socioeconomic, clinical, behavioral, and psychosocial factors, and access-to-care, participants were more likely to have persistent BP control if they were ConclusionLess than half of JHS participants taking antihypertensive medication had persistent BP control, putting them at increased risk for heart failure

A Renewable Source of Human Beige Adipocytes for Development of Therapies to Treat Metabolic Syndrome.

Molecular- and cellular-based therapies have the potential to reduce obesity-associated disease. In response to cold, beige adipocytes form in subcutaneous white adipose tissue and convert energy stored in metabolic substrates to heat, making them an attractive therapeutic target. We developed a robust method to generate a renewable source of human beige adipocytes from induced pluripotent stem cells (iPSCs). Developmentally, these cells are derived from FOXF

A Renewable Source of Human Beige Adipocytes for Development of Therapies to Treat Metabolic Syndrome

Summary: Molecular- and cellular-based therapies have the potential to reduce obesity-associated disease. In response to cold, beige adipocytes form in subcutaneous white adipose tissue and convert energy stored in metabolic substrates to heat, making them an attractive therapeutic target. We developed a robust method to generate a renewable source of human beige adipocytes from induced pluripotent stem cells (iPSCs). Developmentally, these cells are derived from FOXF1+ mesoderm and progress through an expandable mural-like mesenchymal stem cell (MSC) to form mature beige adipocytes that display a thermogenically active profile. This includes expression of uncoupling protein 1 (UCP1) concomitant with increased uncoupled respiration. With this method, dysfunctional adipogenic precursors can be reprogrammed and differentiated into beige adipocytes with increased thermogenic function and anti-diabetic secretion potential. This resource can be used to (1) elucidate mechanisms that underlie the control of beige adipogenesis and (2) generate material for cellular-based therapies that target metabolic syndrome in humans. : Su et al. demonstrate a method for producing beige adipocytes from human induced pluripotent stem cells in a stepwise manner through defined precursor lineages. This renewable resource provides a developmental framework to study human beige adipogenesis and can be used to develop treatments for obesity-related disorders. Keywords: adipogenesis, beige adipocytes, UCP1, metabolic syndrome, diabetes, mesoder