title: Gene expression profile of mouse fibroblasts exposed to a biodegradable iron alloy for stents.
abstract: Iron-based materials could constitute an interesting option for cardiovascular biodegradable stent applications due to their superior ductility compared to their counterparts - magnesium alloys. Since the predicted degradation rate of pure iron is considered slow, manganese (35% w/w), an alloying element for iron, was explored to counteract this problem through the powder metallurgy process (Fe-35 Mn). However, manganese presents a high cytotoxic potential; thus its effect on cells must first be established. Here, we established the gene expression profile of mouse 3T3 fibroblasts exposed to Fe-35 Mn degradation products in order to better understand cell response to potentially cytotoxic degradable metallic material (DMM). Mouse 3T3 cells were exposed to degradation products eluting through tissue culture insert filter (3 μm pore size) containing cytostatic amounts of 3.25 mg ml(-1) of Fe-35 Mn powder, 0.25 mg ml(-1) of pure Mn powder or 5 mg ml(-1) of pure iron powder for 24 h. We then conducted a gene expression profiling study from these cells. Exposure of 3T3 cells to Fe-35 Mn was associated with the up-regulation of 75 genes and down-regulation of 59 genes, while 126 were up-regulated and 76 down-regulated genes in the presence of manganese. No genes were found regulated for the iron powder. When comparing the GEP of 3T3 fibroblasts in the presence of Fe-35 Mn and Mn, 68 up-regulated and 54 down-regulated genes were common. These results were confirmed by quantitative RT-PCR for a subset of these genes. This GEP study could provide clues about the mechanism behind degradation products effects on cells of the Fe-35 Mn alloy and may help in the appraisal of its potential for DMM applications.
authors.affiliation: Laboratory for Biomaterials and Bioengineering, Department of Mining, Metallurgy and Materials Engineering, Pav. Adrien-Pouliot, 1745-E, Laval University, 1065 Ave de la Médicine, Québec City, QC, Canada G1V 0A6; Laval Hospital Research Center/Institut Universitaire de Cardiologie et de Pneumologie de Québec, Department of Medicine, Laval University, 2725 Chemin Ste-Foy, Québec City, QC, Canada G1V 4G5.
authors.forename: Agung
authors.initials: A
authors.lastname: Purnama
authors.forename: Hendra
authors.initials: H
authors.lastname: Hermawan
authors.forename: Serge
authors.initials: S
authors.lastname: Champetier
authors.forename: Diego
authors.initials: D
authors.lastname: Mantovani
authors.forename: Jacques
authors.initials: J
authors.lastname: Couet
mesh_terms: D016475:3T3 Cells; D020341:Absorbable Implants; D000497:Alloys / Q000494:pharmacology*; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D002452:Cell Count; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D063990:Gene Ontology; D007501:Iron / Q000494:pharmacology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D015607:Stents; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000497:Alloys; D001672:Biocompatible Materials; D007501:Iron
keywords: Degradable metals; Fibroblasts; Gene expression profiles; Stents