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.
Bibliographical noteFunding Information:
This work was supported by grants ( R01-EB000244-27 and R01-DE016516-03 ) from the National Institutes of Health . This work was also supported by the Basic Science Research Program ( 2010–0022037 ) through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology and Yonsei University Research Fund ( 2010-7-0089 ), Republic of Korea.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science