title: Therapeutic angiogenesis using genetically engineered human endothelial cells.
abstract: Cell therapy holds promise as a method for the treatment of ischemic disease. However, one significant challenge to the efficacy of cell therapy is poor cell survival in vivo. Here we describe a non-viral, gene therapy approach to improve the survival and engraftment of cells transplanted into ischemic tissue. We have developed biodegradable poly(β-amino esters) (PBAE) nanoparticles as vehicles to genetically modify human umbilical vein endothelial cells (HUVECs) with vascular endothelial growth factor (VEGF). VEGF transfection using these nanoparticles significantly enhanced VEGF expression in HUVECs, compared with a commercially-available transfection reagent. Transfection resulted in the upregulation of survival factors, and improved viability under simulated ischemic conditions. In a mouse model of hindlimb ischemia, VEGF nanoparticle transfection promoted engraftment of HUVECs into mouse vasculature as well as survival of transplanted HUVECs in ischemic tissues, leading to improved angiogenesis and ischemic limb salvage. This study demonstrates that biodegradable polymer nanoparticles may provide a safe and effective method for genetic engineering of endothelial cells to enhance therapeutic angiogenesis.
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Son
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Park
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Green
authors.forename: Said
authors.initials: S
authors.lastname: Bogatyrev
authors.forename: Ying
authors.initials: Y
authors.lastname: Mei
authors.forename: Sohyun
authors.initials: S
authors.lastname: Park
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D000818:Animals; D005260:Female; D006614:Hindlimb; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000473:pathology; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D018919:Neovascularization, Physiologic; D010957:Plasmids; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D014162:Transfection / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000737:chemistry / Q000502:physiology*
chemical_list: D011108:Polymers; D042461:Vascular Endothelial Growth Factor A; C507253:poly(beta-amino ester)