Isolation and transduction of monocytes: promising vehicles for therapeutic arteriogenesis.
OBJECTIVE
Augmentation of collateral vessel growth (arteriogenesis) is of particular clinical interest for the treatment of vascular occlusive disease. Monocytes play a key role for arteriogenesis. They localize to areas of collateral development and create a highly arteriogenic environment. "Homing" of ex vivo genetically engineered monocytes could therapeutically be exploited for augmentation of arteriogenesis. However, isolation and ex vivo transduction of monocytes is problematic.


METHODS
In this study, we established a valid method of monocyte isolation from peripheral blood and evaluated different in vitro transduction methods.


RESULTS
Our results revealed that liposomes and electroporation were unsuccessful for monocyte transduction. However, high-efficiency gene transfer (almost 95%) was achieved by adenoviral infection. Subsequent homing of virally transduced monocytes to sites of arteriogenesis could be demonstrated.


CONCLUSIONS
Our study may offer a new method for the augmentation of arteriogenesis, all of which makes the ultimate goal of applying this strategy to humans for therapy of vascular disease eminently attractive.
Department of Internal Medicine II/Cardiology, University of Technology, Fetscherstrasse 76, Dresden, 01307, Germany. joerg_herold@hotmail.com
Joerg
J
Herold
Harald
H
Tillmanns
Zhou
Z
Xing
Ruth H
RH
Strasser
Ruediger C
RC
Braun-Dullaeus
D000256:Adenoviridae; D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D002469:Cell Separation / Q000379:methods*; D003097:Collateral Circulation / Q000502:physiology; D015870:Gene Expression; D005818:Genetic Engineering; D009000:Monocytes / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D011817:Rabbits; D014161:Transduction, Genetic / Q000379:methods*