PMID- 24594369
OWN - NLM
STAT- MEDLINE
DCOM- 20161019
LR  - 20180816
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 24
IP  - 12
DP  - 2015
TI  - BDNF Pretreatment of Human Embryonic-Derived Neural Stem Cells Improves Cell 
      Survival and Functional Recovery After Transplantation in Hypoxic-Ischemic 
      Stroke.
PG  - 2449-61
LID - 10.3727/096368914X679354 [doi]
AB  - Intra-arterial neural stem cell (NSC) therapy has the potential to improve 
      long-term outcomes after stroke. Here we evaluate if pretreatment of NSCs with 
      brain-derived neurotrophic factor (BDNF) prior to transplantation improves cell 
      engraftment and functional recovery following hypoxic-ischemic (HI) stroke. Human 
      embryonic-derived NSCs with or without BDNF pretreatment (1 h, 100 ng/ml) were 
      transplanted 3 days after HI stroke. Functional recovery was assessed using the 
      horizontal ladder test. Cell engraftment was evaluated using bioluminescence 
      imaging (BLI) and histological counts of SC121(+) cells. Fluoro-Jade C (FJC) and 
      NeuN stains were used to evaluate neuroprotection. The effect of BDNF on NSCs was 
      analyzed using a migration assay, immunocytochemistry, Luminex proteomic assay, 
      and RT-qPCR.BLI analysis demonstrated significantly higher photon flux in the 
      BDNF-treated NSC group compared to untreated NSC (p = 0.049) and control groups 
      (p = 0.0021) at 1 week after transplantation. Immunohistochemistry confirmed 
      increased transplanted cell survival in the cortex (p = 0.0126) and hippocampus 
      (p = 0.0098) of animals injected with BDNF-treated NSCs compared to untreated 
      NSCs. Behavioral testing revealed that the BDNF-treated NSC group demonstrated 
      increased sensorimotor recovery compared to the untreated NSC and control groups 
      (p < 0.001) over the 1-month period (p < 0.001) following transplantation. A 
      significant improvement in performance was found in the BDNF-treated NSC group 
      compared to the control group at 14, 21, and 28 (p < 0.05) days after 
      transplantation. The cortex and hippocampus of the BDNF-treated NSC group had 
      significantly more SC121(+) NSCs (p = 0.0125, p = 0.0098), fewer FJC(+) neurons 
      (p = 0.0370, p = 0.0285), and a higher percentage of NeuN(+) expression (p = 
      0.0354) in the cortex compared to the untreated NSC group. BDNF treatment of NSCs 
      resulted in significantly greater migration to SDF-1, secretion of M-CSF, VEGF, 
      and expression of CXCR4, VCAM-1, Thrombospondins 1 and 2, and BDNF. BDNF 
      pretreatment of NSCs results in higher initial NSC engraftment and survival, 
      increased neuroprotection, and greater functional recovery when compared to 
      untreated NSCs.
FAU - Rosenblum, Sahar
AU  - Rosenblum S
AD  - Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Smith, Tenille N
AU  - Smith TN
FAU - Wang, Nancy
AU  - Wang N
FAU - Chua, Joshua Y
AU  - Chua JY
FAU - Westbroek, Erick
AU  - Westbroek E
FAU - Wang, Kendrick
AU  - Wang K
FAU - Guzman, Raphael
AU  - Guzman R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140303
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Receptors, Chemokine)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Adhesion Molecules/biosynthesis
MH  - Cell Differentiation
MH  - Cell Line
MH  - Cell Movement
MH  - Cell Survival
MH  - Cell- and Tissue-Based Therapy/*methods
MH  - Cerebral Cortex/cytology
MH  - Chemokines, CXC/biosynthesis
MH  - Embryonic Stem Cells/cytology/*transplantation
MH  - HEK293 Cells
MH  - Hippocampus/cytology
MH  - Humans
MH  - Hypoxia-Ischemia, Brain/pathology/*therapy
MH  - Male
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Neural Stem Cells/cytology/*transplantation
MH  - Receptors, Chemokine/biosynthesis
MH  - Recovery of Function
MH  - Stroke/pathology/*therapy
EDAT- 2014/03/07 06:00
MHDA- 2016/11/12 06:00
CRDT- 2014/03/06 06:00
PHST- 2014/03/06 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2016/11/12 06:00 [medline]
AID - content-ct0985rosen [pii]
AID - 10.3727/096368914X679354 [doi]
PST - ppublish
SO  - Cell Transplant. 2015;24(12):2449-61. doi: 10.3727/096368914X679354. Epub 2014 
      Mar 3.