PMID- 23887634
OWN - NLM
STAT- MEDLINE
DCOM- 20140501
LR  - 20230619
IS  - 2041-4889 (Electronic)
VI  - 4
IP  - 7
DP  - 2013 Jul 25
TI  - Differentiation of adipose-derived stem cells into Schwann cell phenotype induces 
      expression of P2X receptors that control cell death.
PG  - e743
LID - 10.1038/cddis.2013.268 [doi]
AB  - Schwann cells (SCs) are fundamental for development, myelination and regeneration 
      in the peripheral nervous system. Slow growth rate and difficulties in harvesting 
      limit SC applications in regenerative medicine. Several molecules, including 
      receptors for neurosteroids and neurotransmitters, have been suggested to be 
      implicated in regulating physiology and regenerative potential of SCs. 
      Adipose-derived stem cells (ASCs) can be differentiated into SC-like phenotype 
      (dASC) sharing morphological and functional properties with SC, thus representing 
      a valid SC alternative. We have previously shown that dASC express 
      gamma-aminobutyric-acid receptors, which modulate their proliferation and 
      neurotrophic potential, although little is known about the role of other 
      neurotransmitters in ASC. In this study, we investigated the expression of 
      purinergic receptors in dASC. Using reverse transriptase (RT)-PCR, western blot 
      analyses and immunocytochemistry, we have demonstrated that ASCs express P2X3, 
      P2X4 and P2X7 purinoceptors. Differentiation of ASCs towards glial phenotype was 
      accompanied by upregulation of P2X4 and P2X7 receptors. Using Ca(2+)-imaging 
      techniques, we have shown that stimulation of purinoceptors with adenosine 
      5'-triphosphate (ATP) triggers intracellular Ca(2+) signals, indicating 
      functional activity of these receptors. Whole-cell voltage clamp recordings 
      showed that ATP and BzATP induced ion currents that can be fully inhibited with 
      specific P2X7 antagonists. Finally, using cytotoxicity assays we have shown that 
      the increase of intracellular Ca(2+) leads to dASC death, an effect that can be 
      prevented using a specific P2X7 antagonist. Altogether, these results show, for 
      the first time, the presence of functional P2X7 receptors in dASC and their link 
      with critical physiological processes such as cell death and survival. The 
      presence of these novel pharmacological targets in dASC might open new 
      opportunities for the management of cell survival and neurotrophic potential in 
      tissue engineering approaches using dASC for nerve repair.
FAU - Faroni, A
AU  - Faroni A
AD  - Faculty of Medical and Human Sciences, The University of Manchester, Manchester, 
      UK. alessandro.faroni@manchester.ac.uk
FAU - Rothwell, S W
AU  - Rothwell SW
FAU - Grolla, A A
AU  - Grolla AA
FAU - Terenghi, G
AU  - Terenghi G
FAU - Magnaghi, V
AU  - Magnaghi V
FAU - Verkhratsky, A
AU  - Verkhratsky A
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130725
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Receptors, Purinergic P2X)
SB  - IM
MH  - Adipocytes/cytology/*drug effects
MH  - Cell Death/drug effects
MH  - Cell Differentiation
MH  - Humans
MH  - Phenotype
MH  - Receptors, Purinergic P2X/*metabolism
MH  - Schwann Cells/cytology/*metabolism
MH  - Stem Cells/cytology/*drug effects
MH  - Survival Analysis
MH  - Up-Regulation
PMC - PMC3730438
EDAT- 2013/07/28 06:00
MHDA- 2014/05/03 06:00
PMCR- 2013/07/01
CRDT- 2013/07/27 06:00
PHST- 2013/04/07 00:00 [received]
PHST- 2013/05/24 00:00 [revised]
PHST- 2013/06/19 00:00 [accepted]
PHST- 2013/07/27 06:00 [entrez]
PHST- 2013/07/28 06:00 [pubmed]
PHST- 2014/05/03 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - cddis2013268 [pii]
AID - 10.1038/cddis.2013.268 [doi]
PST - epublish
SO  - Cell Death Dis. 2013 Jul 25;4(7):e743. doi: 10.1038/cddis.2013.268.