PMID- 24677069
OWN - NLM
STAT- MEDLINE
DCOM- 20150911
LR  - 20211021
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 50
IP  - 2
DP  - 2014 Oct
TI  - Interaction between nonviral reprogrammed fibroblast stem cells and trophic 
      factors for brain repair.
PG  - 673-84
LID - 10.1007/s12035-014-8680-2 [doi]
AB  - There are currently no known treatment options that actually halt or permanently 
      reverse the pathology evident in any neurodegenerative condition. Arguably, one 
      of the most promising avenues for creating viable neuronal treatments could 
      involve the combined use of cell replacement and gene therapy. Given the 
      complexity of the neurodegenerative process, it stands to reason that adequate 
      therapy should involve not only the replacement of loss neurons/synapses but also 
      the interruption of multiple pro-death pathways. Thus, we propose the use of stem 
      cells that are tailored to express specific trophic factors, thereby potentially 
      encouraging synergistic effects between the stem cell properties and those of the 
      trophic factors. The trophic factors, brain-derived neurotropic factor (BDNF), 
      glial cell-derived neurotropic factor (GDNF), fibroblast growth factor (FGF) 2, 
      and insulin-like growth factor (IGF) 1, in particular, have demonstrated 
      neuroprotective actions in a number of animal models. Importantly, we use a 
      nonviral approach, thereby minimizing the potential risk for DNA integration and 
      tumor formation. The present study involved the development of a nonviral 
      reprogramming system to transform adult mature mouse fibroblasts into progressive 
      stages of cell development. We also tailored these stem cells to individually 
      express each of the trophic factors, including BDNF, GDNF, FGF2, and IGF1. 
      Significantly, central infusion of BDNF-expressing stem cells prevented the in 
      vivo loss of neurons associated with infusion of the endotoxin, 
      lipopolysaccharide (LPS). This is particularly important in light of the role of 
      inflammatory processes that are posited to play in virtually all 
      neurodegenerative states. Hence, the present results support the utility of using 
      combined gene and cell-targeting approaches for neuronal pathology.
FAU - Liu, G
AU  - Liu G
AD  - Department of Neuroscience, Carleton University, 327 Life Sciences Research 
      Building, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada.
FAU - Anisman, H
AU  - Anisman H
FAU - Bobyn, J
AU  - Bobyn J
FAU - Hayley, S
AU  - Hayley S
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140328
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
SB  - IM
MH  - Animals
MH  - Brain/metabolism/*pathology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Differentiation/physiology
MH  - Cell Survival/drug effects
MH  - Fibroblasts/*metabolism
MH  - Glial Cell Line-Derived Neurotrophic Factor/metabolism
MH  - Mice
MH  - Nerve Degeneration/*pathology
MH  - Nerve Growth Factors/metabolism
MH  - Neuroglia/metabolism
MH  - Neurons/*metabolism
MH  - Rats, Sprague-Dawley
MH  - Stem Cells/*metabolism
EDAT- 2014/03/29 06:00
MHDA- 2015/09/12 06:00
CRDT- 2014/03/29 06:00
PHST- 2013/11/28 00:00 [received]
PHST- 2014/03/11 00:00 [accepted]
PHST- 2014/03/29 06:00 [entrez]
PHST- 2014/03/29 06:00 [pubmed]
PHST- 2015/09/12 06:00 [medline]
AID - 10.1007/s12035-014-8680-2 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2014 Oct;50(2):673-84. doi: 10.1007/s12035-014-8680-2. Epub 2014 
      Mar 28.