Isolation and transduction of monocytes: promising vehicles for therapeutic arteriogenesis
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BACKGROUND AND AIMS: 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. CONCLUSION: 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.
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