Evaluation of a near-senescent human dermal fibroblast cell line and effect of amelogenin.

BACKGROUND: Fibroblast senescence may delay healing of chronic wounds. OBJECTIVES: To characterize a chronic human dermal fibroblast cell line (CRL-7815) with near-senescent properties, cell proliferation and production of wound-healing modulating cytokines, and biosynthesis and remodelling of collagen were compared with normal human dermal fibroblasts. Also, the response of CRL-7815 fibroblasts to the extracellular matrix protein amelogenin that is beneficial in the treatment of stalled chronic wounds was studied. METHODS: Fibroblast proliferation was monitored by time-resolved growth curves and factors secreted into the culture medium containing 10% fetal bovine serum were measured by enzyme-linked immunosorbent assays. Fibroblast-mediated reorganization was examined in three-dimensional type I collagen matrices. RESULTS: Cell proliferation over 9 days was significantly (P < 0.01) slower for CRL-7815 than for normal fibroblasts. Amelogenin at 1 mg mL(-1) increased (P < 0.01) CRL-7815 proliferation to the level of the normal fibroblasts. The neutrophil chemoattractant interleukin (IL)-8 was low while the constitutive production of monocyte chemoattractant protein (MCP)-1 was highly elevated in medium from cultured CRL-7815 fibroblasts. Amelogenin augmented IL-8 but attenuated MCP-1 secretion in CRL-7815 fibroblasts. The elevated vascular endothelial growth factor production in CRL-7815 fibroblasts was further increased with amelogenin while increased type I collagen synthesis by CRL-7815 was reduced with 0.1 mg mL(-1) amelogenin. The dramatically impaired collagen matrix remodelling with CRL-7815 fibroblasts (P < 0.001) was slightly improved with amelogenin (P = 0.0011). CONCLUSIONS: The near-senescent cell line CRL-7815 shares functional anomalies with fibroblasts isolated from nonhealing chronic cutaneous wounds. Amelogenin has the capacity to switch chronic fibroblasts into an acute-like phenotype.

Long-term psychosocial adjustment following pediatric liver transplantation.

This study assessed long-term psychosocial adjustment to pediatric liver transplantation in 146 patients aged 4-25 yr, who had received a transplant 2-12 yr previously. Evaluations of psychosocial adjustment and related variables were based on the Harter Self-Perception Profiles for children, Child Behavior Checklist (CBCL), and children's academic level. Up to the age of 8 yr, transplant children as a group did not perceive themselves as less competent than healthy peers. Gender effects were characterized by older girls perceiving significantly less scholastic cognitive competence than their healthy peers. Adolescent and young adult boys had significantly lower global self-worth and lower perceived athletic competence than their healthy peers. In comparison to normative data of healthy children, CBCL parent-reported scores revealed significant deficits in competences for all age groups. Only for the older boys, however, did these deficits reported by the parents reach a pathological level. The majority of transplant children also had significantly higher problem scores, but they remained within the normal range, except for the older boys whose internalizing problems reached a borderline level. Our results suggest that liver transplantation does not substantially affect schooling. Regardless of statistically significant differences in psychosocial adjustment, the majority of the transplant children functioned at a normal level. For adolescent and young adult boys, however, the presence of problems and the lack of competences observed by parents and by the youngsters themselves reached borderline to pathological levels. Our findings stress the importance of psychological post-transplant follow-up with increased attention of caregivers to child and parental concerns about their long-term psychosocial adjustment process.