PMID- 24837134
OWN - NLM
STAT- MEDLINE
DCOM- 20150915
LR  - 20220331
IS  - 1937-335X (Electronic)
IS  - 1937-3341 (Print)
IS  - 1937-3341 (Linking)
VI  - 20
IP  - 23-24
DP  - 2014 Dec
TI  - Stem cells of the apical papilla regulate trigeminal neurite outgrowth and 
      targeting through a BDNF-dependent mechanism.
PG  - 3089-100
LID - 10.1089/ten.TEA.2013.0347 [doi]
AB  - Regenerative endodontic procedures have become a valuable alternative for the 
      treatment of immature teeth with pulp necrosis. In addition to resolution of 
      periradicular pathosis and promotion of continued root development, positive 
      vitality testing has been observed in some regenerative clinical cases. 
      Importantly, the positive response to electric stimulation of the regenerated 
      tissue requires targeting of periradicular axons into the previously empty root 
      canal space. However, the mechanism by which this process occurs is largely 
      unknown. Since stem cells of the apical papilla (SCAP) have been proposed to 
      populate the root canal following regenerative endodontic procedures, we 
      hypothesized that SCAP regulate neurite outgrowth and axonal targeting. To test 
      this hypothesis, we established primary co-cultures of human SCAP and rat 
      trigeminal neurons, and performed neurite outgrowth assays using ELISA and 
      confocal microscopy to determine the effect of increasing concentration of SCAP 
      on the total neurite outgrowth and axonal targeting. In addition, we evaluated 
      whether SCAP evoked axonal targeting in vivo using a matrigel subcutaneous 
      implant assay. Data were analyzed by ANOVA with Bonferroni's post hoc test, and 
      significance was set at p<0.05. The results demonstrated that SCAP release a 
      soluble factor that regulates neurite outgrowth from cultured trigeminal neurons. 
      Next, we demonstrated that this effect is completely abolished by pretreatment 
      with a neutralizing antibody to brain-derived neurotrophic factor (BDNF), but not 
      by antibodies to other neurotrophins. Further, SCAP release BDNF in a 
      concentration-dependent manner as detected by ELISA, and trigger directed axonal 
      targeting both in vitro and in vivo as demonstrated by microfluidic and matrigel 
      implant experiments, respectively. Collectively, these results suggest that SCAP 
      may be responsible for the chemical signal driving axons to target regenerated 
      tissue via a BDNF-dependent mechanism.
FAU - de Almeida, Jose Flavio A
AU  - de Almeida JF
AD  - 1 Department of Restorative Dentistry, Endodontics Division, Piracicaba Dental 
      School, University of Campinas , Piracicaba, Sao Paulo, Brazil .
FAU - Chen, Paul
AU  - Chen P
FAU - Henry, Michael A
AU  - Henry MA
FAU - Diogenes, Anibal
AU  - Diogenes A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Tissue Eng Part A
JT  - Tissue engineering. Part A
JID - 101466659
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 9061-61-4 (Nerve Growth Factor)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Glial Cell Line-Derived Neurotrophic Factor/metabolism
MH  - Male
MH  - Mice, SCID
MH  - Nerve Growth Factor/metabolism
MH  - Neurites/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stem Cells/*metabolism
MH  - Trigeminal Nerve/*cytology/*metabolism
PMC - PMC4259194
EDAT- 2014/05/20 06:00
MHDA- 2015/09/16 06:00
PMCR- 2015/12/01
CRDT- 2014/05/20 06:00
PHST- 2014/05/20 06:00 [entrez]
PHST- 2014/05/20 06:00 [pubmed]
PHST- 2015/09/16 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - 10.1089/ten.tea.2013.0347 [pii]
AID - 10.1089/ten.TEA.2013.0347 [doi]
PST - ppublish
SO  - Tissue Eng Part A. 2014 Dec;20(23-24):3089-100. doi: 10.1089/ten.TEA.2013.0347.