Aditya S Pandey1, James D San Antonio2, Sankar Addya3, Saul Surrey4, Paolo Fortina5, Elisabeth J Van Bockstaele6, Erol Veznedaroglu7. 1. Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: adityap@med.umich.edu. 2. Operations, Stryker Corporation, Malvern, Pennsylvania, USA. 3. Department of Cancer Biology, Cancer Genomics Laboratory, Kimmel Cancer Center, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania, USA. 4. Department of Medicine, Cardeza Foundation for Hematologic Research, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania, USA. 5. 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. 6. Department of Neurosurgery, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania, USA. 7. Stroke and Cerebrovascular Center of New Jersey, Capital Health System, Trenton, New Jersey, USA.
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.
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: Carmelo J Panetta; Katsumi Miyauchi; David Berry; Robert D Simari; David R Holmes; Robert S Schwartz; Noel M Caplice Journal: Hum Gene Ther Date: 2002-02-10 Impact factor: 5.695
Authors: Juhana Frösen; Anna Piippo; Anders Paetau; Marko Kangasniemi; Mika Niemelä; Juha Hernesniemi; Juha Jääskeläinen Journal: Stroke Date: 2004-08-19 Impact factor: 7.914
Authors: Asita Sarrafzadeh; Daniel Haux; Ingeborg Küchler; Wolfgang R Lanksch; Andreas W Unterberg Journal: J Neurosurg Date: 2004-03 Impact factor: 5.115