Paper Title
Potential Of Autologous Circulating Cd34+45- Source Cells To Inhibit Smooth Muscle Cell Dedifferentiation For Intracranial And Vascular Stent Applications

Balloon angioplasty ± stenting is often complicated by restenosis, initiated in part by endothelial denudation, leading to smooth muscle cell dedifferentiation and proliferation. These complications could possibly be mitigated by reendothelialization of the stented vessel lumen including the stent surface using autologous cells. Circulating CD34+CD45- cells are the source cells of late-outgrowth endothelial progenitor cells and can be isolated by FDA-approved immunomagnetic selection. Our pilot studies tested the hypotheses that the CD34+45- source cells could adhere to (Ti), the bloodcontacting surface material of nitinolintracranial and vascular stents, and that the CD34+45- source cells on Ti would differentiate into endothelial cells with the potential to inhibit smooth muscle cell dedifferentiation. Our results show that the an average of 39.7± 6.0%, 19.7± 2.1%, 14.7± 6.8% ofsource cells remained adherent on Ti under laminal fluid flow shear stress of 10, 15, and 20dynes/cm2 (n=3 for each shear stress). The cells differentiated into endothelial cells on Ti, shown by EC-characteristic cobblestone morphology, Di-Ac-LDL uptake, PECAM-1 positive staining and thrombomodulin expression. Lining bare Ti surfaces with a confluent monolayer of the CD34+45- cellssignificantly reduced the ability of platelets to adhere to those surfaces, with only 149.4 ± 178.0 platelets/mm2 adhered to the cell-lined Ti surfaces, compared to 2372.9 ± 29.2 for the bare surfaces. Further, the CD34+45- source cells showed potential to inhibit SMC dedifferentiation as assessed by increased smooth muscle cell-specific differentiation marker 􀀀-SMA. Future in vivo studies are warranted to investigate the effect of CD34+45- source cells to regenerate damaged endothelium after angioplasty ± stenting by lining the blood-contacting surface of stents and potentially replacing endothelial cells that were sheared off from the vessel lumen. Keywords: Endothelial Progenitor Cell, Stent, Smooth-muscle cell, Immuno-magnetic selection, -SMA, Thrombomodulin