Recently we have developed a methodology for isolation and purification of adult vascular progenitor cells, from several species including humans, that are clonogenic, self renewing and multipotent. These vascular progenitor cells are, to our knowledge, one of the few adult vascular stem cells ever described in humans, other than the multipotent adult progenitor cells (MAPCs), that have multilineage vascular differentiation capacity and unlimited growth potential ex vivo (growing to excess of 120 population doublings). These cells can expanded in culture to form engineered micro and macro-vascular structures or can be implanted in vivo to reconstitute multiple cellular components within injured and repairing arteries.

These findings provide fundamental new insights into the biology of the adult vasculature. Multifaceted opportunities exist to exploit the biology of these cells in terms of novel diagnostics, medical and surgical therapeutics and development of a range of new technologies ranging from tissue engineered vascular conduits and microvascular networks to novel endovascular cell seeded devices. Exploitation of this biology may allow new and innovative approaches to vascular regeneration, post -myocardial infarct repair and revascularization of the peripheral circulation.

Our group was the first to describe the presence of putative smooth muscle progenitor cells in the circulation of humans. Around this time we also published the first definitive evidence of human bone marrow derived smooth muscle precursors participating in atherosclerotic plaque biology. Together these findings prompted in our lab a fundamental re-evaluation of the contribution of circulating cells to smooth muscle biology in vascular disease.

n collaboration with transplant surgery colleagues at Mayo Clinic we showed that recipient cells contribute significantly to intimal smooth muscle in the plaque of transplant vasculopathy. Moreover our finding that~10% of plaque smooth muscle cells are bone marrow derived within 4 years of transplant suggest an active and functionally significant biology that can be exploited to gain new insights into the genesis of atherosclerosis. For instance we have recently used smooth muscle progenitor cells as a cellular assay for predicting the therapeutic efficacy of a number of vascular cytostatic and cytotoxic drugs used on drug eluting stents. We have been able to use these cells as a means of rapidly screening drugs used by the device industry with good predictive success. This assay is currently under patent development and will ultimately be licensed to industry to aid rapid screening of drugs suitable for vascular device interfacing. Moreover we have developed real-time arterial flow assays of in situ adhesion and rolling of putative progenitor cells to activated endothelium and candidate vascular adhesion molecules. This has provided a fertile field for small molecule discovery.

Following the initial discovery of human endothelial outgrowth cells our lab became interested in determining the relationship between these endothelial outgrowth cells and human vascular disease. We have shown that endothelial progenitors have a unique surface integrin profile which allow these cells to attach to specific extracellular matrix proteins and that these cells are phenotypically distinct from smooth muscle progenitor.s Moreover we have demonstrated that EOC are reduced in the presence of vascular disease and that recipient endothelial cells are intimately involved in the biology of transplant vasculopathy in human subjects.

We use state of the art murine, chimeric, vascular injury and molecular models to test hypotheses relating to vascular progenitor homing, engraftment, and differentiation. Moreover we use regulatable transgenesis to address questions relating to lineage, promoter activation, and morphogenesis of vascular progenitor cells.