PMID- 24356107
OWN - NLM
STAT- MEDLINE
DCOM- 20141128
LR  - 20140409
IS  - 1473-558X (Electronic)
IS  - 0959-4965 (Linking)
VI  - 25
IP  - 7
DP  - 2014 May 7
TI  - Creatine supports propagation and promotes neuronal differentiation of inner ear 
      progenitor cells.
PG  - 446-51
LID - 10.1097/WNR.0000000000000112 [doi]
AB  - Long-term propagation of inner ear-derived progenitor/stem cells beyond the third 
      generation and differentiation into inner ear cell types has been shown to be 
      feasible, but challenging. We investigated whether the known neuroprotective 
      guanidine compound creatine (Cr) promotes propagation of inner ear 
      progenitor/stem cells as mitogen-expanded neurosphere cultures judged from the 
      formation of spheres over passages. In addition, we studied whether Cr alone or 
      in combination with brain-derived neurotrophic factor (BDNF) promotes neuronal 
      differentiation of inner ear progenitors. For this purpose, early postnatal rat 
      spiral ganglia, utricle, and organ of Corti-derived progenitors were grown as 
      floating spheres in the absence (controls) or presence of Cr (5 mM) from passage 
      3 onward. Similarly, dissociated sphere-derived cultures were differentiated for 
      14 days in the presence or absence of Cr (5 mM) and spiral ganglia sphere-derived 
      cultures in a combination of Cr with the neurotrophin BDNF (50 ng/ml). We found 
      that the cumulative total number of spheres over all passages was significantly 
      higher after Cr supplementation as compared with controls in all the three inner 
      ear cultures. In contrast, sphere sizes were not affected by the administration 
      of Cr. Administration of Cr during differentiation of spiral ganglia cells 
      resulted in a significantly higher density of beta-III-tubulin-positive cells 
      compared with controls, whereas densities of myosin VIIa-positive cells in 
      cultures of utricle and organ of Corti were not affected by the treatment. 
      Importantly, a combination of Cr with the neurotrophin BDNF resulted in further 
      significantly increased densities of beta-III-tubulin-positive cells in cultures of 
      spiral ganglia cells as compared with single treatments. In sum, Cr promoted 
      continuing propagation of rat inner ear-derived progenitor cells and supported 
      specifically in combination with BDNF the differentiation of neuronal cell types 
      from spiral ganglion-derived spheres.
FAU - Di Santo, Stefano
AU  - Di Santo S
AD  - aInner Ear Research Laboratory, Department of Otorhinolaryngology, Head & Neck 
      Surgery bDepartment of Neurosurgery, Neurocenter and Regenerative Neuroscience 
      Cluster, University of Bern, Inselspital, Bern, Switzerland.
FAU - Mina, Amir
AU  - Mina A
FAU - Ducray, Angelique
AU  - Ducray A
FAU - Widmer, Hans R
AU  - Widmer HR
FAU - Senn, Pascal
AU  - Senn P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuroreport
JT  - Neuroreport
JID - 9100935
RN  - 0 (Tubulin)
RN  - MU72812GK0 (Creatine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Cell Count
MH  - Cell Differentiation/*drug effects
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured
MH  - Creatine/*pharmacology
MH  - Ear, Inner/*cytology
MH  - Linear Models
MH  - Neural Stem Cells/*drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Statistics, Nonparametric
MH  - Tubulin/metabolism
EDAT- 2013/12/21 06:00
MHDA- 2014/12/15 06:00
CRDT- 2013/12/21 06:00
PHST- 2013/12/21 06:00 [entrez]
PHST- 2013/12/21 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.1097/WNR.0000000000000112 [doi]
PST - ppublish
SO  - Neuroreport. 2014 May 7;25(7):446-51. doi: 10.1097/WNR.0000000000000112.