Abstract
Object. 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 124-135 |
| Number of pages | 12 |
| Journal | Journal of Neurosurgery |
| Volume | 103 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 2005 |
| Externally published | Yes |
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Keywords
- Differentiation
- Endothelial cell
- Neural element
- Pluripotent cell
- Progenitor cell
- Rat
- Regeneration
ASJC Scopus subject areas
- Clinical Neurology
- Neuroscience(all)
Cite this
Multi-germ layer lineage central nervous system repair : Nerve and vascular cell generation by embryonic stem cells transplanted in the injured brain. / Vadivelu, Sudhakar; Platik, Marina M.; Choi, Luke; Lacy, Molly L.; Shah, Aarti R.; Qu, Yun; Holekamp, Terrence F.; Becker, Daniel; Gottlieb, David I.; Gidday, Jeffrey M.; McDonald, John W.
In: Journal of Neurosurgery, Vol. 103, No. 1, 07.2005, p. 124-135.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Multi-germ layer lineage central nervous system repair
T2 - Nerve and vascular cell generation by embryonic stem cells transplanted in the injured brain
AU - Vadivelu, Sudhakar
AU - Platik, Marina M.
AU - Choi, Luke
AU - Lacy, Molly L.
AU - Shah, Aarti R.
AU - Qu, Yun
AU - Holekamp, Terrence F.
AU - Becker, Daniel
AU - Gottlieb, David I.
AU - Gidday, Jeffrey M.
AU - McDonald, John W.
PY - 2005/7
Y1 - 2005/7
N2 - Object. 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.
AB - Object. 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.
KW - Differentiation
KW - Endothelial cell
KW - Neural element
KW - Pluripotent cell
KW - Progenitor cell
KW - Rat
KW - Regeneration
UR - http://www.scopus.com/inward/record.url?scp=24944454294&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=24944454294&partnerID=8YFLogxK
U2 - 10.3171/jns.2005.103.1.0124
DO - 10.3171/jns.2005.103.1.0124
M3 - Article
C2 - 16121983
AN - SCOPUS:24944454294
VL - 103
SP - 124
EP - 135
JO - Journal of Neurosurgery
JF - Journal of Neurosurgery
SN - 0022-3085
IS - 1
ER -