Protection of nigral neurons by GDNF-engineered marrow cell transplantation

Kun Woo Park, Martin A. Eglitis, M. Maral Mouradian

Research output: Contribution to journalArticle

79 Citations (Scopus)

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 languageEnglish
Pages (from-to)315-323
Number of pages9
JournalNeuroscience Research
Volume40
Issue number4
DOIs
Publication statusPublished - 2001 Aug
Externally publishedYes

Keywords

  • Bone marrow
  • GDNF
  • Gene therapy
  • MPTP
  • Parkinson
  • Transplantation
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Neuroscience(all)

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