Rationale: Recent reports have demonstrated that signals from vascular
endothelial cells are necessary for
organogenesis that may precede
vasculogenesis. However, the origin of these neovascular cells in regenerating tissue has not been clarified. Objective: Here we tested the hypothesis that adult
neural stem cells (NSCs) can differentiate into vascular lineage, as well as
neural lineage, in the process of collaborative
organogenesis. Methods and Results: NSCs, clonally isolated from
mouse brain, were shown to develop
endothelial and
smooth muscle phenotypes in vitro. To elucidate whether NSCs can simultaneously differentiate into vascular and
neural cells in vivo,
genetically labeled NSCs were administered to
mice with unilateral
sciatic nerve crush
injury or operatively induced
brain and
myocardial ischemia. Two weeks later,
necropsy examination disclosed recruitment of the labeled NSCs to sites of
injury differentiating into
vascular cells (
endothelial cells and
vascular smooth muscle cells) and
Schwann cells in regenerating
nerve. Similarly, NSC-derived
vascular cells/
astrocytes and
endothelial cells were identified in
ischemic brain tissue and
capillaries in
myocardium 2 weeks following transplantation, respectively. Conclusions: These findings, concurrent
vasculogenesis and
neurogenesis from a common
stem cell, suggest that certain
somatic stem cells are capable of differentiating into not only
somatic cells of identity but also into
vascular cells for tissue regeneration.
