Analysis of the effects of surface treatments on nickel release from nitinol wires and their impact on candidate gene expression in endothelial cells.

Nitinol has many applications in the medical device industry, however the large amount of nickel, a known allergen and carcinogen remains a serious concern. Studies have already shown that nickel ions induce the differential expression of a range of genes, including cell adhesion molecules. This study sought to determine the level of nickel ions released from nitinol wires that had been surface treated by etching and mechanically polishing or etching and pickling compared to untreated wires and determine the biological impact of the wires on human umbilical vein endothelial cells (HUVECs) at the transcriptional level by real-time PCR. The four different wire types were incubated in media and the amount of nickel eluted after 24, 48 and 72 h was determined. HUVECs were then cultured and incubated with the four different wire types for 24 h. Cells were harvested, RNA isolated and real-time PCR was carried out to measure the expression levels of ICAM-1, VCAM-1 and E-selectin, three known inflammatory mediators, compared to control cells. E-selectin, a marker of endothelial cell injury and activation was found to be significantly up-regulated in cells incubated with wires that released the highest amount of nickel ions. Nickel ions are released from nitinol wires with certain surface characteristics and these ions have a biological effect on HUVECs in vitro.

An investigation into the effect of surface roughness of stainless steel on human umbilical vein endothelial cell gene expression.

The surface properties of vascular devices dictate the initial postimplantation reactions that occur and thus the efficacy of the implantation procedure. Over the last number of years, a number of different stent designs have emerged and stents are generally polished to a mirror finish during the manufacturing procedure. This study sought to investigate the effect of stainless steel surface roughness on endothelial cell gene expression using an appropriate cell culture in vitro assay system. Stainless steel discs were roughened by shot blasting or polished by mechanical polishing. The surface roughness of the treated and untreated discs was determined by atomic force microscopy (AFM). Cells were seeded on collagen type 1 gels and left to attach for 24 h. Stainless steel discs of varying roughness were then placed in contact with the cells and incubated for 24 h. RNA extractions and quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was then performed to determine the expression levels of candidate genes in the treated cells compared to suitable control cells. E-selectin and vascular cellular adhesion molecule (VCAM-1) were found to be significantly up-regulated in cells incubated with polished and roughened samples, indicating endothelial cell activation and inflammation. This study indicates that the surface roughness of stainless steel is an important surface property in the development of vascular stents.

Global gene expression analysis of the effects of vinblastine on endothelial cells, when eluted from a thermo-responsive polymer.

In-stent restenosis remains a significant problem associated with bare metal stents. This drawback has prompted research into improving stent design and the development of novel coatings, including drug-eluting stents. A number of drug-eluting stents are currently on the market; however, the success rate of these stents in complex situations has been found to be quite low. Thus, there remains potential for the development of more suitable drug-eluting stents. The aims of this study were to use a thermoresponsive polymer to develop a system to locally deliver vinblastine, an antimitotic agent currently used as an anticancer drug, and in addition, assess the effects of this drug at the gene expression level in vitro. An N-isopropylacrylamide/N-tert-butylacrylamide (NiPAAm/NtBAAm) copolymer solution in the ratio 65:35 was prepared and appropriate volumes of vinblastine were added to generate two final drug concentrations of 22 nanomoles/film or 0.022 nanomoles/film. Stainless steel discs (316) were coated with the copolymer solution or this solution containing drug. Human endothelial cells were cultured on collagen type 1 gels and then incubated with the coated discs for 24 h. Gene expression studies using oligonucleotide microarray analysis and quantitative RT-PCR were then performed. Microarray analysis revealed that vinblastine causes the differential expression of a range of genes involved in a variety of different functions, including cell cycle and apoptosis. The changes in expression of some of these genes culminate in cell cycle arrest and apoptotic pathways.

Blast-like cells in the cerebrospinal fluid of young infants: further characterization of clinical setting, morphology and origin.

Blast-like cells in the cerebrospinal fluid (CSF) of neonates have been identified and previously suggested to be of germinal matrix origin. Twelve additional CSF specimens with blast-like cells collected at the University of Texas Medical Branch, Galveston, between 1985-1992 were analyzed. The cytological features of the blast-like cells as well as their associated clinical setting were further characterized by the authors. All patients in the study were young infants with hydrocephalus and nearly all underwent placement of a ventriculoperitoneal (VP) shunt at the time the CSF specimen was collected. In addition, a cytologic preparation of germinal matrix cells obtained from an autopsy specimen was analyzed, which closely resembled the blast-like cells. These data provide additional evidence that blast-like cells originate from the germinal matrix.