Multi-germ layer lineage central nervous system repair: nerve and vascular cell generation by embryonic stem cells transplanted in the injured brain.
OBJECTIVE
To restore proper function to a damaged central nervous system (CNS) through transplantation, it is necessary to replace both neural and nonneural elements that arise from different germ layers in the embryo. Mounting evidence indicates the importance of signals related to vasculogenesis in governing neural proliferation and differentiation in early CNS development. Here, the authors examined whether embryonic stem cell (ESC)-derived progenitors can selectively generate both neural and endothelial cells after transplantation in the damaged CNS.


METHODS
Injections of 20 nmol N-methyl-D-aspartate created a unilateral striatal injury in 7-day-old rats. One week postinjury, murine ESCs, neural-induced with retinoic acid, were transplanted into the injured striatum. Histological staining, laser confocal microscopy, and transmission electron microscopy of grafted ESCs were performed 1 week posttransplantation.


CONCLUSIONS
Transplanted ESCs differentiated into neural cells, which segregated into multiple pools and formed neurons that conformed to host cytoarchitecture. The ESCs also generated endothelial cells, which integrated with host cells to form chimeric vasculature. The combination of ESC pluripotentiality and multiple germ layer differentiation provides a new conceptual framework for CNS repair.
Vadivelu
Sudhakar
S
Center for the Study of Nervous System Injury and the Restorative Treatment and Research Program, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Platik
Marina M
MM
Choi
Luke
L
Lacy
Molly L
ML
Shah
Aarti R
AR
Qu
Yun
Y
Holekamp
Terrence F
TF
Becker
Daniel
D
Gottlieb
David I
DI
Gidday
Jeffrey M
JM
McDonald
John W
JW
D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D003342:Corpus Striatum / Q000293:injuries* / Q000601:surgery* / Q000648:ultrastructure; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D008297:Male; D009474:Neurons / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation