Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury.
The present study was undertaken to examine multifaceted therapeutic effects of vascular endothelial growth factor (VEGF) in a rat spinal cord injury (SCI) model, focusing on its capability to stimulate proliferation of endogenous glial progenitor cells. Neural stem cells (NSCs) can be genetically m...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2656622?pdf=render |
| _version_ | 1818499701894283264 |
|---|---|
| author | Hyuk Min Kim Dong Hoon Hwang Jong Eun Lee Seung U Kim Byung G Kim |
| author_facet | Hyuk Min Kim Dong Hoon Hwang Jong Eun Lee Seung U Kim Byung G Kim |
| author_sort | Hyuk Min Kim |
| collection | DOAJ |
| description | The present study was undertaken to examine multifaceted therapeutic effects of vascular endothelial growth factor (VEGF) in a rat spinal cord injury (SCI) model, focusing on its capability to stimulate proliferation of endogenous glial progenitor cells. Neural stem cells (NSCs) can be genetically modified to efficiently transfer therapeutic genes to diseased CNS. We adopted an ex vivo approach using immortalized human NSC line (F3 cells) to achieve stable and robust expression of VEGF in the injured spinal cord. Transplantation of NSCs retrovirally transduced to overexpress VEGF (F3.VEGF cells) at 7 days after contusive SCI markedly elevated the amount of VEGF in the injured spinal cord tissue compared to injection of PBS or F3 cells without VEGF. Concomitantly, phosphorylation of VEGF receptor flk-1 increased in F3.VEGF group. Stereological counting of BrdU+ cells revealed that transplantation of F3.VEGF significantly enhanced cellular proliferation at 2 weeks after SCI. The number of proliferating NG2+ glial progenitor cells (NG2+/BrdU+) was also increased by F3.VEGF. Furthermore, transplantation of F3.VEGF increased the number of early proliferating cells that differentiated into mature oligodendrocytes, but not astrocytes, at 6 weeks after SCI. F3.VEGF treatment also increased the density of blood vessels in the injured spinal cord and enhanced tissue sparing. These anatomical results were accompanied by improved BBB locomotor scores. The multifaceted effects of VEGF on endogenous gliogenesis, angiogenesis, and tissue sparing could be utilized to improve functional outcomes following SCI. |
| first_indexed | 2024-12-10T20:33:01Z |
| format | Article |
| id | doaj.art-f3c55cd9675c4fb79654e5500c2ed972 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T20:33:01Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f3c55cd9675c4fb79654e5500c2ed9722022-12-22T01:34:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0143e498710.1371/journal.pone.0004987Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury.Hyuk Min KimDong Hoon HwangJong Eun LeeSeung U KimByung G KimThe present study was undertaken to examine multifaceted therapeutic effects of vascular endothelial growth factor (VEGF) in a rat spinal cord injury (SCI) model, focusing on its capability to stimulate proliferation of endogenous glial progenitor cells. Neural stem cells (NSCs) can be genetically modified to efficiently transfer therapeutic genes to diseased CNS. We adopted an ex vivo approach using immortalized human NSC line (F3 cells) to achieve stable and robust expression of VEGF in the injured spinal cord. Transplantation of NSCs retrovirally transduced to overexpress VEGF (F3.VEGF cells) at 7 days after contusive SCI markedly elevated the amount of VEGF in the injured spinal cord tissue compared to injection of PBS or F3 cells without VEGF. Concomitantly, phosphorylation of VEGF receptor flk-1 increased in F3.VEGF group. Stereological counting of BrdU+ cells revealed that transplantation of F3.VEGF significantly enhanced cellular proliferation at 2 weeks after SCI. The number of proliferating NG2+ glial progenitor cells (NG2+/BrdU+) was also increased by F3.VEGF. Furthermore, transplantation of F3.VEGF increased the number of early proliferating cells that differentiated into mature oligodendrocytes, but not astrocytes, at 6 weeks after SCI. F3.VEGF treatment also increased the density of blood vessels in the injured spinal cord and enhanced tissue sparing. These anatomical results were accompanied by improved BBB locomotor scores. The multifaceted effects of VEGF on endogenous gliogenesis, angiogenesis, and tissue sparing could be utilized to improve functional outcomes following SCI.http://europepmc.org/articles/PMC2656622?pdf=render |
| spellingShingle | Hyuk Min Kim Dong Hoon Hwang Jong Eun Lee Seung U Kim Byung G Kim Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury. PLoS ONE |
| title | Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury. |
| title_full | Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury. |
| title_fullStr | Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury. |
| title_full_unstemmed | Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury. |
| title_short | Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury. |
| title_sort | ex vivo vegf delivery by neural stem cells enhances proliferation of glial progenitors angiogenesis and tissue sparing after spinal cord injury |
| url | http://europepmc.org/articles/PMC2656622?pdf=render |
| work_keys_str_mv | AT hyukminkim exvivovegfdeliverybyneuralstemcellsenhancesproliferationofglialprogenitorsangiogenesisandtissuesparingafterspinalcordinjury AT donghoonhwang exvivovegfdeliverybyneuralstemcellsenhancesproliferationofglialprogenitorsangiogenesisandtissuesparingafterspinalcordinjury AT jongeunlee exvivovegfdeliverybyneuralstemcellsenhancesproliferationofglialprogenitorsangiogenesisandtissuesparingafterspinalcordinjury AT seungukim exvivovegfdeliverybyneuralstemcellsenhancesproliferationofglialprogenitorsangiogenesisandtissuesparingafterspinalcordinjury AT byunggkim exvivovegfdeliverybyneuralstemcellsenhancesproliferationofglialprogenitorsangiogenesisandtissuesparingafterspinalcordinjury |