Concurrent vasculogenesis and neurogenesis from adult neural stem cells.
BACKGROUND
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.


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.
Ii
Masaaki
M
Group of Vascular Regeneration Research, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Nishimura
Hiromi
H
Sekiguchi
Haruki
H
Kamei
Naosuke
N
Yokoyama
Ayumi
A
Horii
Miki
M
Asahara
Takayuki
T
D053687:Adult Stem Cells / Q000378:metabolism* / Q000637:transplantation; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D002450:Cell Communication; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000637:transplantation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000637:transplantation; D018919:Neovascularization, Physiologic; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism* / Q000637:transplantation; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D015398:Signal Transduction; D018874:Spheroids, Cellular; D033581:Stem Cell Transplantation; D013997:Time Factors
D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins