PMID- 23109183
OWN - NLM
STAT- MEDLINE
DCOM- 20130830
LR  - 20220408
IS  - 1613-6829 (Electronic)
IS  - 1613-6810 (Print)
IS  - 1613-6810 (Linking)
VI  - 9
IP  - 4
DP  - 2013 Feb 25
TI  - Microfluidic investigation of BDNF-enhanced neural stem cell chemotaxis in CXCL12 
      gradients.
PG  - 585-95
LID - 10.1002/smll.201202208 [doi]
AB  - In vivo studies have suggested that gradients of CXCL12 (aka stromal cell-derived 
      factor 1alpha) may be critical for neural stem cell (NSC) migration during brain 
      development and neural tissue regeneration. However, traditional in vitro 
      chemotaxis tools are limited by unstable concentration gradients and the 
      inability to decouple cell migration directionality and speed. These limitations 
      have restricted the reproducible and quantitative analysis of neuronal migration, 
      which is required for mechanism-based studies. Using a microfluidic gradient 
      generator, nestin and Sox-2 positive human embryonic NSC chemotaxis is quantified 
      within a linear and stable CXCL12 gradient. While untreated NSCs are not able to 
      chemotax within CXCL12 gradients, pre-treatment of the cells with brain-derived 
      neurotrophic factor (BDNF) results in significant chemotactic, directional 
      migration. BDNF pre-treatment has no effect on cell migration speed, which 
      averages about 1 mum min(-1). Quantitative analysis determines that CXCL12 
      concentrations above 9.0 nM are above the minimum activation threshold, while 
      concentrations below 14.7 nM are below the saturation threshold. Interestingly, 
      although inhibitor studies with AMD 3100 revealed that CXCL12 chemotaxis requires 
      receptor CXCR4 activation, BDNF pre-treatment is found to have no profound 
      effects on the mRNA levels or surface presentation of CXCR4 or the putative CXCR7 
      scavenger receptor. The microfluidic study of NSC migration within stable 
      chemokine concentration profiles provides quantitative analysis as well as new 
      insight into the migratory mechanism underlying BDNF-induced chemotaxis towards 
      CXCL12.
CI  - Copyright (c) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Xu, Hui
AU  - Xu H
AD  - Stanford University, Stanford, CA 94305-4045, USA.
FAU - Heilshorn, Sarah C
AU  - Heilshorn SC
LA  - eng
GR  - R21-AR062359-01/AR/NIAMS NIH HHS/United States
GR  - DP2 OD006477/OD/NIH HHS/United States
GR  - 1T32-HL098049-01A1/HL/NHLBI NIH HHS/United States
GR  - 1DP2-OD006477-01/OD/NIH HHS/United States
GR  - T32 HL098049/HL/NHLBI NIH HHS/United States
GR  - R21 AR062359/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121026
PL  - Germany
TA  - Small
JT  - Small (Weinheim an der Bergstrasse, Germany)
JID - 101235338
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chemokine CXCL12)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Chemokine CXCL12/chemistry/*pharmacology
MH  - Chemotaxis/*drug effects
MH  - Humans
MH  - *Microfluidic Analytical Techniques
MH  - Neural Stem Cells/*cytology/*drug effects
PMC - PMC3984949
MID - NIHMS496539
EDAT- 2012/10/31 06:00
MHDA- 2013/08/31 06:00
PMCR- 2014/04/13
CRDT- 2012/10/31 06:00
PHST- 2012/09/07 00:00 [received]
PHST- 2012/10/31 06:00 [entrez]
PHST- 2012/10/31 06:00 [pubmed]
PHST- 2013/08/31 06:00 [medline]
PHST- 2014/04/13 00:00 [pmc-release]
AID - 10.1002/smll.201202208 [doi]
PST - ppublish
SO  - Small. 2013 Feb 25;9(4):585-95. doi: 10.1002/smll.201202208. Epub 2012 Oct 26.