Vascular Development by a Non-Angiogenic Mechanism: Evidence for Neural Stem Cell Plasticity

2006 new Scholar Award in aging

Adult neural stem cells are brain-specific somatic stem cells that localize to interfaces with the vasculature within proliferative clusters comprised of neuronal, glial, endothelial and smooth muscle cells. This concentration of newly-formed cells and vascular structures define the extracellular environment or "niche" of the neural stem cell.

The traditional view suggests that new endothelial cells within the stem cell niche arise by angiogenesis, the process whereby blood vessel-associated endothelial cells proliferate to form new vascular branches directed at oxygen- and nutrient-deprived tissue. Believed to be the paradigm for vascularization in adult, angiogenesis has been proposed to be a key determinant underlying the growth of solid tumors, the metastasis of cancerous cells and the accumulation of amyloid beta peptide associated with Alzheimerís disease. Unexpectedly, we found that instructive, intercellular signals divert neural stem cells, which were originally proposed to differentiate to only neurons and glial cells, from the neural lineages to vascular endothelial and smooth muscle cells.

The mechanism by which neural stem cells convert to endothelial and smooth muscle cells is referred to as stem cell plasticity, a poorly understood phenomenon whereby tissue-specific stem cells broaden their developmental repertoires and differentiate to cells of another lineage. Thus, neural stem cell plasticity rather than angiogenesis may account for a significant proportion of blood vessel generation in brain, expanding the importance of the adult neural stem cell in maintaining the cellular composition and function of the central nervous system. Our goal is to determine whether the neural stem cell plays an important, non-angiogenic role in the physiological and pathological remodeling of the vasculature within the adult central nervous system.