Stem cell – based therapies for central nervous system disorders are intensely pursued. Such approaches can be
divided into two categories: Transplantation-based, and those that aim to pharmacologically target the endogenous stem
cell population in the tissue. Endogenous stem cell – based strategies avoid the problem of immune incompatibility
between the host and the grafted cells. They also avoid the placement of a large amount of cells in confined areas, a
manipulation which alters the characteristics of the neurovascular microenvironment. We show here that massive
pharmacological activation (increase in cell numbers) of the endogenous neural stem cell population in the adult rodent
brain maintains the cytoarchitecture of the neurovascular niche. Distances between adjacent stem cells (identified by
expression of Hes3) are maintained above a minimum. Hes3+ cells maintain their physical association with blood vessels.
These results also suggest a mechanism by which the activation signal from the lateral ventricle can be propagated to
areas a long distance away from the lateral ventricles, through autocrine/paracrine actions between adjacent Hes3+ cells,
along blood vessels. Finally, powerful effects of angiopoietin 2 on Hes3+ cells help explain the prevalence of proliferating
endogenous neural stem cells close to the subventricular zone (an area of high angiopoietin 2 concentration) and the
quiescent state of stem cells away from the ventricles and their tight physical association with blood vessels (which
express high levels of angiopoietin 1, a cytokine that opposes angiopoietin 2 functions).
Keywords: Endogenous, neural stem cells, brain, degenerative disease, endogenous stem cell population, immune, Hes3+ cells, subventricular zone, angiopoietin 2, cytokine
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