PMID- 28646200
OWN - NLM
STAT- MEDLINE
DCOM- 20190107
LR  - 20190107
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jun 23
TI  - Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF.
PG  - 4153
LID - 10.1038/s41598-017-03592-1 [doi]
LID - 4153
AB  - Mesenchymal stem cells (MSCs) have been used for cell-based therapies in 
      regenerative medicine, with increasing importance in central and peripheral 
      nervous system repair. However, MSCs grafting present disadvantages, such as, a 
      high number of cells required for transplantation and low survival rate when 
      transplanted into the central nervous system (CNS). In line with this, MSCs 
      secretome which present on its composition a wide range of molecules 
      (neurotrophins, cytokines) and microvesicles, can be a solution to surpass these 
      problems. However, the effect of MSCs secretome in axonal elongation is poorly 
      understood. In this study, we demonstrate that application of MSCs secretome to 
      both rat cortical and hippocampal neurons induces an increase in axonal length. 
      In addition, we show that this growth effect is axonal intrinsic with no 
      contribution from the cell body. To further understand which are the molecules 
      required for secretome-induced axonal outgrowth effect, we depleted brain-derived 
      neurotrophic factor (BDNF) from the secretome. Our results show that in the 
      absence of BDNF, secretome-induced axonal elongation effect is lost and that 
      axons present a reduced axonal growth rate. Altogether, our results demonstrate 
      that MSCs secretome is able to promote axonal outgrowth in CNS neurons and this 
      effect is mediated by BDNF.
FAU - Martins, Luis F
AU  - Martins LF
AD  - CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 
      Portugal.
AD  - PhD programme in Experimental Biology and Biomedicine (PDBEB), Center for 
      Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
AD  - Institute for Interdisciplinary Research, University of Coimbra, Coimbra, 
      Portugal.
FAU - Costa, Rui O
AU  - Costa RO
AD  - CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 
      Portugal.
AD  - Institute for Interdisciplinary Research, University of Coimbra, Coimbra, 
      Portugal.
FAU - Pedro, Joana R
AU  - Pedro JR
AD  - CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 
      Portugal.
FAU - Aguiar, Paulo
AU  - Aguiar P
AUID- ORCID: 0000-0003-4164-5713
AD  - INEB - Instituto de Engenharia Biomedica, i3S - Instituto de Investigacao e 
      Inovacao em Saude, Porto, Portugal.
FAU - Serra, Sofia C
AU  - Serra SC
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal.
FAU - Teixeira, Fabio G
AU  - Teixeira FG
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal.
FAU - Sousa, Nuno
AU  - Sousa N
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal.
FAU - Salgado, Antonio J
AU  - Salgado AJ
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal.
FAU - Almeida, Ramiro D
AU  - Almeida RD
AD  - CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 
      Portugal. ramirodalmeida@gmail.com.
AD  - School of Health, Polytechnic of Porto (ESS-IPP), Porto, Portugal. 
      ramirodalmeida@gmail.com.
AD  - Institute for Interdisciplinary Research, University of Coimbra, Coimbra, 
      Portugal. ramirodalmeida@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170623
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Proteome)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Central Nervous System/cytology
MH  - Culture Media, Conditioned/pharmacology
MH  - Humans
MH  - Mesenchymal Stem Cells/drug effects/*metabolism
MH  - Microfluidics
MH  - Models, Neurological
MH  - *Neuronal Outgrowth/drug effects
MH  - Neurons/drug effects/metabolism
MH  - Proteome/*metabolism
MH  - Rats, Wistar
MH  - Receptor, trkB/metabolism
MH  - Umbilical Cord/blood supply/cytology
PMC - PMC5482809
COIS- The authors declare that they have no competing interests.
EDAT- 2017/06/25 06:00
MHDA- 2019/01/08 06:00
PMCR- 2017/06/23
CRDT- 2017/06/25 06:00
PHST- 2017/02/06 00:00 [received]
PHST- 2017/05/02 00:00 [accepted]
PHST- 2017/06/25 06:00 [entrez]
PHST- 2017/06/25 06:00 [pubmed]
PHST- 2019/01/08 06:00 [medline]
PHST- 2017/06/23 00:00 [pmc-release]
AID - 10.1038/s41598-017-03592-1 [pii]
AID - 3592 [pii]
AID - 10.1038/s41598-017-03592-1 [doi]
PST - epublish
SO  - Sci Rep. 2017 Jun 23;7(1):4153. doi: 10.1038/s41598-017-03592-1.