Abstract
Marrow stromal cells, which have many characteristics of stem cells, populate various non-hematopoietic tissues including the brain. In the present study, the cDNA for the dopaminergic neurotrophic factor Glial Cell Line-Derived Neurotrophic Factor (GDNF) was delivered using marrow cells in the mouse 1-Methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) model of Parkinson's disease. Following cross-sex intravenous bone marrow transplantation with male donor cells that had been transduced with GDNF (GDNF-BMT) or with non-manipulated marrow (Control-BMT), female recipient mice were subjected to systemic MPTP injections. Eight weeks after neurotoxin exposure, more tyrosine hydroxylase immunoreactive nigral neurons and striatal terminal density were observed in the GDNF-BMT mice compared with the Control-BMT group. In addition, following the expected initial behavioral hyperactivity in both groups, a significant difference in motor activity was detected between the two groups. GDNF immunoreactive male donor marrow derived cells were detected in the brains of GDNF-BMT mice but not in controls. These data indicate that marrow derived cells that seed the brain can express biologically active gene products and, therefore, can function as effective vehicles for therapeutic gene transfer to the brain.
| Original language | English |
|---|---|
| Pages (from-to) | 315-323 |
| Number of pages | 9 |
| Journal | Neuroscience Research |
| Volume | 40 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2001 Jan 1 |
| Externally published | Yes |
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Keywords
- Bone marrow
- GDNF
- Gene therapy
- MPTP
- Parkinson
- Transplantation
- Tyrosine hydroxylase
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Protection of nigral neurons by GDNF-engineered marrow cell transplantation. / Park, Kun Woo; Eglitis, Martin A.; Mouradian, M. Maral.
In: Neuroscience Research, Vol. 40, No. 4, 01.01.2001, p. 315-323.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Protection of nigral neurons by GDNF-engineered marrow cell transplantation
AU - Park, Kun Woo
AU - Eglitis, Martin A.
AU - Mouradian, M. Maral
PY - 2001/1/1
Y1 - 2001/1/1
N2 - Marrow stromal cells, which have many characteristics of stem cells, populate various non-hematopoietic tissues including the brain. In the present study, the cDNA for the dopaminergic neurotrophic factor Glial Cell Line-Derived Neurotrophic Factor (GDNF) was delivered using marrow cells in the mouse 1-Methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) model of Parkinson's disease. Following cross-sex intravenous bone marrow transplantation with male donor cells that had been transduced with GDNF (GDNF-BMT) or with non-manipulated marrow (Control-BMT), female recipient mice were subjected to systemic MPTP injections. Eight weeks after neurotoxin exposure, more tyrosine hydroxylase immunoreactive nigral neurons and striatal terminal density were observed in the GDNF-BMT mice compared with the Control-BMT group. In addition, following the expected initial behavioral hyperactivity in both groups, a significant difference in motor activity was detected between the two groups. GDNF immunoreactive male donor marrow derived cells were detected in the brains of GDNF-BMT mice but not in controls. These data indicate that marrow derived cells that seed the brain can express biologically active gene products and, therefore, can function as effective vehicles for therapeutic gene transfer to the brain.
AB - Marrow stromal cells, which have many characteristics of stem cells, populate various non-hematopoietic tissues including the brain. In the present study, the cDNA for the dopaminergic neurotrophic factor Glial Cell Line-Derived Neurotrophic Factor (GDNF) was delivered using marrow cells in the mouse 1-Methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) model of Parkinson's disease. Following cross-sex intravenous bone marrow transplantation with male donor cells that had been transduced with GDNF (GDNF-BMT) or with non-manipulated marrow (Control-BMT), female recipient mice were subjected to systemic MPTP injections. Eight weeks after neurotoxin exposure, more tyrosine hydroxylase immunoreactive nigral neurons and striatal terminal density were observed in the GDNF-BMT mice compared with the Control-BMT group. In addition, following the expected initial behavioral hyperactivity in both groups, a significant difference in motor activity was detected between the two groups. GDNF immunoreactive male donor marrow derived cells were detected in the brains of GDNF-BMT mice but not in controls. These data indicate that marrow derived cells that seed the brain can express biologically active gene products and, therefore, can function as effective vehicles for therapeutic gene transfer to the brain.
KW - Bone marrow
KW - GDNF
KW - Gene therapy
KW - MPTP
KW - Parkinson
KW - Transplantation
KW - Tyrosine hydroxylase
UR - http://www.scopus.com/inward/record.url?scp=0034895752&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034895752&partnerID=8YFLogxK
U2 - 10.1016/S0168-0102(01)00242-5
DO - 10.1016/S0168-0102(01)00242-5
M3 - Article
C2 - 11463477
AN - SCOPUS:0034895752
VL - 40
SP - 315
EP - 323
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
IS - 4
ER -