ABSTRACT
Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR(+) precursors of human foreskin can be ascribed to the Schwann (CD56(+)) and perivascular (CD56(-)) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR(+)CD56(+) Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread.
Subject(s)
Cell Lineage , Dermis/cytology , Neural Stem Cells/cytology , Schwann Cells/cytology , Adolescent , Adult , Aged , Animals , CD56 Antigen/genetics , CD56 Antigen/metabolism , Cell Differentiation/genetics , Cells, Cultured , Child , Child, Preschool , Dermis/metabolism , Foreskin/cytology , Gene Expression Profiling , Humans , Infant , Male , Mice , Microscopy, Confocal , Middle Aged , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neural Stem Cells/metabolism , Neurons/cytology , Neurons/metabolism , Receptors, Nerve Growth Factor/genetics , Receptors, Nerve Growth Factor/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Schwann Cells/metabolism , Young AdultABSTRACT
BACKGROUND: Hypoalbuminemia is associated with poor prognosis in patients with certain chronic diseases, such as end-stage renal disease and cancer. Although low serum albumin is common in patients with heart failure (HF), the relationship between albumin and HF prognosis has not been well characterized. This study investigated the effect of serum albumin level on survival in patients with advanced HF. METHODS: We analyzed 1726 systolic HF patients (age 52 +/- 13 years, ejection fraction [EF] 23% +/- 7%) followed at a university HF center. Albumin level was determined at initial referral. Patients were divided by into groups based on presence of hypoalbuminemia (< or = 3.4 g/dL). Mean albumin was 3.8 +/- 0.6 g/dL, and 25% of patients had hypoalbuminemia. RESULTS: Patients with and without low albumin levels were similar in age, HF etiology, and EF. Hypoalbuminemia was associated with higher New York Heart Association (NYHA) class, higher serum urea nitrogen, creatinine level, C-reactive protein, and B-type natriuretic peptide but lower levels of sodium, hemoglobin, and cholesterol. In patients with BMI < 25 kg/m(2), 27% had albumin < or = 3.4 g/dL, compared to 22% of those with BMI > or = 25 kg/m(2) (P < .01). One-year survival was 66% in patients with and 83% in those without hypoalbuminemia (P < .0001). Risk-adjusted hazard ratios for 1- and 5-year mortality were 2.2 (1.4-3.3) and 2.2 (1.4-3.2), respectively. CONCLUSIONS: Hypoalbuminemia is common in HF and is independently associated with increased risk of death in HF. Further investigation of pathophysiologic mechanisms underlying hypoalbuminemia in HF is warranted.
