title: Mechanisms of endothelial cell attachment, proliferation, and differentiation on 4 types of platinum-based endovascular coils.
abstract: OBJECTIVE
  A subarachnoid hemorrhage is neurologically devastating, with 50% of patients becoming disabled or deceased. Advent of Guglielmi detachable coils in 1995 permitted endovascular treatment of cerebral aneurysms. Coiling is efficacious and safe, but durability needs improvement, as nearly 20% of patients require further invasive intervention secondary to aneurysm recurrence. The aim of this study is to develop an in vitro model of endothelial cell (EC) proliferation and differentiation on four types of platinum-based coils, using gene expression profiling to understand EC biology as they colonize and differentiate on coils.
  
  
  METHODS
  Human umbilical vein ECs were grown in vitro on platinum coil segments. Growth patterns were assessed as a function of coil type. Gene expression profiles for coil attached versus coil unattached ECs were determined using immunohistochemistry and gene array analysis.
  
  
  RESULTS
  ECs showed rapid, robust attachment to all coil types. Some detachment occurred within 24-48 hours. Significant growth of remaining attached cells occurred during the next week, creating a confluence on coils and within coil grooves. Similar growth curve results were obtained with human brain ECs on platinum-based coil surfaces. Differentiation markers in attached cells (α(1), α(2), β(1) integrins) were expressed on immunostaining, whereas microarray gene expression revealed 48 up-regulated and 68 down-regulated genes after 24-hour growth on coils. Major pathways affected as a function of time of colonization on coils and coil type included those involved in regulation of cell cycle and cell signaling.
  
  
  CONCLUSIONS
  We developed an in vitro model for evaluating endothelialization of platinum coils to optimize coil design to support robust EC colonization and differentiation.
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: adityap@med.umich.edu.
authors.forename: Aditya S
authors.initials: AS
authors.lastname: Pandey
authors.affiliation: Operations, Stryker Corporation, Malvern, Pennsylvania, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: San Antonio
authors.affiliation: Department of Cancer Biology, Cancer Genomics Laboratory, Kimmel Cancer Center, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
authors.forename: Sankar
authors.initials: S
authors.lastname: Addya
authors.affiliation: Department of Medicine, Cardeza Foundation for Hematologic Research, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
authors.forename: Saul
authors.initials: S
authors.lastname: Surrey
authors.affiliation: Department of Cancer Biology, Cancer Genomics Laboratory, Kimmel Cancer Center, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania, USA; Department of Molecular Medicine, University La Sapienza, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fortina
authors.affiliation: Department of Neurosurgery, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Van Bockstaele
authors.affiliation: Stroke and Cerebrovascular Center of New Jersey, Capital Health System, Trenton, New Jersey, USA.
authors.forename: Erol
authors.initials: E
authors.lastname: Veznedaroglu
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D004621:Embolization, Therapeutic / Q000295:instrumentation* / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D002532:Intracranial Aneurysm / Q000628:therapy; D010984:Platinum; D013345:Subarachnoid Hemorrhage / Q000628:therapy; D023822:Tissue Engineering / Q000379:methods; D059467:Transcriptome
chemical_list: D010984:Platinum
keywords: Cerebral aneurysms; Coils; Endothelial cells; Subarachnoid hemorrhage; Tissue engineering