Genetically modified CD34(+) cells as cellular vehicles for gene delivery into areas of angiogenesis in a rhesus model

To develop a cellular vehicle able to reach systemically disseminated areas of angiogenesis, we sought to exploit the natural tropism of circulating e ndothelial progenitor cells (EPCs). Primate CD34(+) EPCs were genetically m odified with high efficiency and minimal toxicity using a non-replicative h erpes virus vector These EPCs localized in a skin autograft model of angiog enesis in rhesus monkeys, and sustained the expression of a reporter gene f or several weeks while circulating in the blood. In animals infused with au tologous CD34(+) EPCs transduced with a thymidine kinase-encoding herpes vi rus, skin autografts and subcutaneous Matrigel pel lets impregnated with va scular growth factors underwent necrosis or accelerated regression after ad ministration of ganciclovir. Importantly, the whole intervention was perfec tly well tolerated. The accessibility, easy manipulation, lack of immunogen icity of the autologous CD34+ cell vehicles, and tropism for areas of angio genesis render autologous CD34+ circulating endothelial progenitors as idea l candidates for exploration of their use as cellular vehicles when systemi c gene delivery to those areas is required.