| Project/Area Number |
15390448
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Orthopaedic surgery
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
SEICHI Atsushi The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (70236066)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Shinichi Research Institute National Rehabilitation Center, Division of Motor Dysfunction, Primary Investigator, 運動機能系障害研究部, 主任研究官 (30282560)
NAKAMURA Kozo The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (60126133)
|
|---|
| Project Period (FY) |
2003 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2004: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥3,800,000 (Direct Cost: ¥3,800,000)
|
|---|
| Keywords | spinal cord injury / neural progenitor / gene transfer / transcription factor / neuron / oligodendrocyte / サイトカイン |
|---|
| Research Abstract |
Neurons and oligodendrocytes in the adult spinal cord are vulnerable to various insults. Despite the occurrence of endogenous neural progenitors, replacement of these cell types after damage occurs to only a limited extent. The environment of injured tissue is thus thought to restrict the regenerative capacity of endogenous cells : strategies for overcoming such restriction remain to be developed. In this study, we first developed a retrovirus-mediated genetic marking method to examine the properties of endogenous neural progenitors in the injured spinal cord. We show that the green fluorescent protein (GFP)-expressing recombinant retrovirus pMXIG preferentially infected cells expressing NG2,Olig2,and Nkx2.2 in injured tissue. Such GFP-labeled NG2^+/Olig2^s+/Nkx2.2^+ cells formed neurospheres and differentiated into neurons, astrocytes, and oligodendrocytes in vitro, and thus exhibited the features of neural progenitors. Production of new neurons or mature oligodendrocytes by these GFP^+ progenitors, however, was not detectable in situ. We found that direct administration of growth factors into the lesioned spinal cord could, and overexpression of the neurogenic transcription factors Neurogenin2 and Mash1 enhanced the production and maturation of new neurons and oligodendrocytes by endogenous progenitors, respectively. The effects of these manipulations suggested that neurogenesis and oligodendrogenesis are restricted by the environment at multiple steps, each of which is a potential target for pharmacological and genetic manipulations. These results raise the possibility of a cell replacement strategy utilizing endogenous progenitors, alternative to transplantation of exogenous cells, to repair the injured spinal cord.
|
