Development of in vitro endothelialized drug-eluting stent using human peripheral blood-derived endothelial progenitor cells

Jitsuro Tsukada, Frederic Wolf, Felix Vogt, Nicole Schaaps, Sven Thoröe-Boveleth, Hans Keijdener, Joachim Jankowski, Hiroko Tsukada, Stefan Jockenhövel, Masahiro Jinzaki, Thomas Schmitz-Rode, Petra Mela

研究成果: Article査読

抄録

We propose in vitro endothelialization of drug-eluting stents (DES) to overcome late stent thrombosis by directly introducing late-outgrowth human endothelial progenitor cells (EPCs) at the target site utilizing abluminal DES. Isolated EPCs were confirmed as late-outgrowth EPCs by flow cytometric analysis. Abluminally paclitaxel-loaded stents were seeded with different cell concentrations and durations to determine optimal seeding conditions, in both uncrimped and crimped configurations. The seeding yield was determined by evaluating the percent coverage of the stent struts' area. The EPC-seeded DES were exposed to arterial shear stress to evaluate the effect of high shear stress on EPCs. To investigate how much paclitaxel elutes during the seeding procedure, a pharmacokinetic analysis was performed. Finally, to validate the proof of concept, EPC-seeded DES were placed on a fibrin matrix with and without smooth muscle cells (SMCs) and cultured for 3 days under perfusion. The seeding procedure resulted in 47% and 26% coverage of the stent surface in uncrimped and crimped conditions, respectively. After the optimal seeding, almost 99% of drug was still available. When EPC-seeded DES were placed on a fibrin matrix and cultured for 3 days, the EPCs confluently covered the stent surface and spread to the surrounding fibrin gel. When EPC-seeded DES were placed on SMC-containing fibrin layers, cells in contact with the struts died. EPCs can be successfully seeded onto DES without losing drug-eluting capability, and EPCs exhibit sufficient proliferative ability. EPC-seeded DES may combine early re-endothelialization ability with the antirestenotic effectiveness of DES.

本文言語English
ページ(範囲)1415-1427
ページ数13
ジャーナルJournal of Tissue Engineering and Regenerative Medicine
14
10
DOI
出版ステータスPublished - 2020 10 1

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

フィンガープリント 「Development of in vitro endothelialized drug-eluting stent using human peripheral blood-derived endothelial progenitor cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル