Telomerized human microvasculature is functional in vivo

Previously we showed the superior in vitro survival of human telomerase rev erse transcriptase (hTERT)transduced human endothelial cells (EC). Here we show that retroviral-mediated transduction of hTERT in human dermal microva scular EC (HDMEC) results in cell lines that form microvascular structures when subcutaneously implanted in severe combined immunodeficiency (SCID) mi ce. Anti-human type IV collagen basement membrane immunoreactivity and visu alization of enhanced green fluorescent protein (eGFP)labeled microvessels confirmed the human origin of these capillaries. No human vasculature was o bserved after implantation of HT1080 fibrosarcoma cells, 293 human embryoni c kidney cells, or human skin fibroblasts. Intravascular red fluorescent mi crospheres injected into host circulation were found within green "telomeri zed" microvessels, indicating functional murine-human vessel anastamoses. W hereas primary HDMEC-derived vessel density decreased with time, telomerize d HDMEC maintained durable vessels six weeks after xenografting. Modulation of implant vessel density by exposure to different angiogenic and angiosta tic factors demonstrated the utility of this system for the study of human microvascular remodeling in vivo.