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Radially symmetric endothelial cell replacement and lentiviral targeting in vessels by the use of magnetic nanoparticles (MNPs)
Author(s) -
Wenzel Daniela,
Vosen Sarah,
Rieck Sarah,
Zimmermann Katrin,
Heidsieck Alexandra,
Neidler Sarah,
Mykhaylyk Olga,
Gleich Bernhard,
Plank Christian,
Pfeifer Alexander,
Fleischmann Bernd K
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1127.1
Subject(s) - endothelial stem cell , microbiology and biotechnology , endothelium , transduction (biophysics) , ex vivo , chemistry , vasculogenesis , in vivo , biology , in vitro , biochemistry , endocrinology
Endothelial cell damage often occurs in vascular disease such as atherosclerosis resulting in loss of vasoregulation and/or thrombosis. To restore endothelial function we have established novel methods to either combine site‐specific endothelial cell positioning with lentiviral transduction in arteries or directly transduce the vascular endothelium in situ. Therefore, we have designed a special magnetic device to obtain a radially symmetric endothelial cell or lentivirus deposition on the vascular wall. Lentivirus is coupled to magnetic nanoparticles (MNPs) enabling the efficient transduction of endothelial cells by application of magnetic force. As a proof of concept we show that bovine pulmonary arterial endothelial cells (bPAECs) and human umbilical vein endothelial cells (HUVECs) are efficiently transduced with complexes of MNPs and lentiviral vectors carrying a GFP expression cassette. These cells can be positioned in a radially symmetric manner in an ex vivo flow‐loop system. Moreover, this technique also allows for the direct lentiviral transduction of the murine endothelium in situ, which is proven by GFP expression in the vessel after 4–6 days in culture. We plan to use this approach in combination with the application of therapeutic genes e.g. the endothelial nitric oxide synthase (eNOS) to restore vascular endothelial function ex vivo and in vivo.