Intravenous infusion of GDNF gene-modified human umbilical cord blood CD34+ cells protects against cerebral ischemic injury in spontaneously hypertensive rats.
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 6h 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 peri-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.
Ou
Yali
Y
Department of Cardiology, Xiangya Hospital, Southern Central University, Changsha 410008, China.
Yu
Seongjin
S
Kaneko
Yuji
Y
Tajiri
Naoki
N
Bae
Eunkyung Cate
EC
Chheda
Sonia H
SH
Stahl
Christine E
CE
Yang
Tianlun
T
Fang
Li
L
Hu
Kei
K
Borlongan
Cesar V
CV
Yu
Guolong
G
D000704:Analysis of Variance; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D001522:Behavior, Animal; D002545:Brain Ischemia / Q000235:genetics / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005312:Fetal Blood / Q000166:cytology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods
D018952:Antigens, CD34; D019208:Brain-Derived Neurotrophic Factor; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins