PMID- 28492549
OWN - NLM
STAT- MEDLINE
DCOM- 20180216
LR  - 20181202
IS  - 2041-4889 (Electronic)
VI  - 8
IP  - 5
DP  - 2017 May 11
TI  - Enhanced neuroprotective efficacy of bone marrow mesenchymal stem cells 
      co-overexpressing BDNF and VEGF in a rat model of cardiac arrest-induced global 
      cerebral ischemia.
PG  - e2774
LID - 10.1038/cddis.2017.184 [doi]
AB  - Cardiac arrest-induced global cerebral ischemia injury (CA-GCII) usually leads to 
      a poor neurological outcome without an effective treatment. Bone marrow-derived 
      mesenchymal stem cells (BMMSCs) may provide a potential cell-based therapy 
      against neurologic disorders through induction of brain-derived neurotrophic 
      factor (BDNF) and vascular endothelial growth factor (VEGF). To optimize the 
      neuroprotective efficacy of BMMSCs further, in this study we have derived BMMSCs, 
      which co-overexpress both BDNF and VEGF, and tested them for the treatment of 
      CA-GCII in a rat model. Lentiviruses that express rat BDNF exon IV or VEGF-A were 
      created using the bicistronic shuttle vectors of pLVX-IRES-ZsGreen1 and 
      pLVX-IRES-tdTomato, respectively. BMMSCs that were co-transduced with the 
      engineered lentiviruses with co-overexpression of both BDNF and VEGF along with 
      corresponding fluorescent protein reporters were injected via jugular vein of 
      rats that just recovered from a cardiac arrest. Animals were then scored for 
      neurofunctional deficits and examined for brain pathology and gene expression 
      relevant to the engraftment seven days after the treatments. We demonstrate that 
      anchorage of lentiviral vector-transduced BMMSCs, which co-overexpressed both 
      BDNF and VEGF in the hippocampus and temporal cortex along with significantly 
      ameliorated brain pathology and improved neurofunctional performance in CA-GCII 
      rats after transplantation. These findings provide a proof of concept for the 
      further validation of engineered BMMSCs for the treatment of CA-GCII patients in 
      clinical practice in the future.
FAU - Zhou, Lili
AU  - Zhou L
AD  - Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou 510120, China.
AD  - Department of Emergency Medicine, Institute of Cardiopulmonary Cerebral 
      Resuscitation, Sun Yat-sen University, Guangzhou 510120, China.
FAU - Lin, Qingming
AU  - Lin Q
AD  - Department of Emergency Medicine, Fujian Provincial Hospital, Fujian Medical 
      University, Fuzhou 350001, China.
FAU - Wang, Peng
AU  - Wang P
AD  - Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou 510120, China.
AD  - Department of Emergency Medicine, Institute of Cardiopulmonary Cerebral 
      Resuscitation, Sun Yat-sen University, Guangzhou 510120, China.
FAU - Yao, Lan
AU  - Yao L
AD  - Department of Emergency Medicine, The Fifth Affiliated Hospital, Sun Yat-sen 
      University, Zhuhai 519000, China.
FAU - Leong, Kahong
AU  - Leong K
AD  - Department of Emergency Medicine, Hospital Conde S. Januario, Macau, China.
FAU - Tan, Zhiqun
AU  - Tan Z
AD  - Institute for Memory Impairments and Neurological Disorders, University of 
      California Irvine, Irvine, CA 92697, USA.
AD  - Institute of Precision Medicine, Jining Medical University, Jining 272067, China.
FAU - Huang, Zitong
AU  - Huang Z
AD  - Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou 510120, China.
AD  - Department of Emergency Medicine, Institute of Cardiopulmonary Cerebral 
      Resuscitation, Sun Yat-sen University, Guangzhou 510120, China.
LA  - eng
PT  - Journal Article
DEP - 20170511
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, rat)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*metabolism/pathology
MH  - Brain Ischemia/genetics/metabolism/pathology/*therapy
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics
MH  - Disease Models, Animal
MH  - *Gene Expression Regulation
MH  - Heart Arrest/genetics/metabolism/pathology/*therapy
MH  - Lentivirus
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transduction, Genetic
MH  - Vascular Endothelial Growth Factor A/*biosynthesis/genetics
PMC - PMC5520708
COIS- The authors declare no conflict of interest.
EDAT- 2017/05/12 06:00
MHDA- 2018/02/17 06:00
PMCR- 2017/05/01
CRDT- 2017/05/12 06:00
PHST- 2016/11/22 00:00 [received]
PHST- 2017/03/23 00:00 [revised]
PHST- 2017/03/27 00:00 [accepted]
PHST- 2017/05/12 06:00 [entrez]
PHST- 2017/05/12 06:00 [pubmed]
PHST- 2018/02/17 06:00 [medline]
PHST- 2017/05/01 00:00 [pmc-release]
AID - cddis2017184 [pii]
AID - 10.1038/cddis.2017.184 [doi]
PST - epublish
SO  - Cell Death Dis. 2017 May 11;8(5):e2774. doi: 10.1038/cddis.2017.184.