Journal
BRAIN RESEARCH
Volume 1366, Issue -, Pages 217-225Publisher
ELSEVIER
DOI: 10.1016/j.brainres.2010.09.098
Keywords
Stroke; Neurotrophic factor; Stem cell; Gene therapy; Transplantation
Categories
Funding
- National Natural Science Foundation of China [30572079]
- Chinese Ministry of Education for oversea students
- James and Esther King Biomedical Research Programs [09KB-01-23123, 1KG01-33966]
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This study assessed the potential of intravenous transplantation of human umbilical cord blood (HUCB) CD34+ cells transfected with glial cell line-derived neurotrophic factor (GDNF) gene to exert therapeutic benefits in spontaneous hypertensive rats (SHR) exposed to transient middle cerebral artery occlusion (MCAO). SHR with MCAO were randomly assigned to receive intravenously transplantation of vehicle, the plasmid containing the enhanced green fluorescent protein (pEGFP)-CD34+ cells or pEGFP-GDNF-CD34+ cells at 6 h after stroke. The CD34+ cells transfected with GDNF gene expressed higher levels of GDNF mRNA and protein than nontransfected HUCB CD34+ cells in vitro. At 28 days after transplantation of GDNF gene modified CD34+ cells, significantly more GFP positive cells, neurons, and astrocytes, likely derived from the grafted cells, populated the pen-infarct area compared to those injected with pEGFP-CD34+ cells or vehicle. Furthermore, the stroke animals transplanted with GDNF gene modified CD34+ cells showed a significant increase in GDNF level in the infarcted hemisphere, reduced brain infarction volume, and enhanced functional recovery compared with those that received pEGFP-CD34+ cells. This study supports the use of a combined gene and stem cell therapy for treating stroke. (C) 2010 Elsevier B.V. All rights reserved.
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