PMID- 17013619
OWN - NLM
STAT- MEDLINE
DCOM- 20070731
LR  - 20220716
IS  - 0014-4819 (Print)
IS  - 0014-4819 (Linking)
VI  - 177
IP  - 4
DP  - 2007 Mar
TI  - Time of transplantation and cell preparation determine neural stem cell survival 
      in a mouse model of Huntington's disease.
PG  - 458-70
AB  - Cell replacement therapies for neurodegenerative diseases, using multipotent 
      neural stem cells (NSCs), require above all, a good survival of the graft. In 
      this study, we unilaterally injected quinolinic acid (QA) into the striatum of 
      adult mice and transplanted syngeneic NSCs of enhanced green fluorescent 
      protein-transgenic mice into the lesioned striatum. The injection of QA leads to 
      an excitotoxic lesion with selective cell death of the medium sized spiny 
      neurons, the same cells that are affected in Huntington's disease. In order to 
      investigate the best timing of transplantation for the survival of donor cells, 
      we transplanted the stem cells at 2, 7 and 14 days after injury. In addition, the 
      influence of graft preparation prior to transplantation, i.e., intact 
      neurospheres versus dissociated cell suspension on graft survival was 
      investigated. By far the best survival was found with the combination of early 
      transplantation (i.e., 2 days after QA-lesion) with the use of neurospheres 
      instead of dissociated cell suspension. This might be due to the different states 
      of host's astrocytic and microglia activation which we found to be moderate at 2, 
      but pronounced at 7 and 14 days after QA-lesion. We also investigated brain 
      derived neurotrophic factor (BDNF)-expression in the striatum after QA-lesion and 
      found no significant change in BDNF protein-level. We conclude that already the 
      method of graft preparation of NSCs for transplantation, as well as the timing of 
      the transplantation procedure strongly affects the survival of the donor cells 
      when grafted into the QA-lesioned striatum of adult mice.
FAU - Johann, Verena
AU  - Johann V
AD  - Department of Neurology, University Hospital RWTH, Pauwelsstr. 30, 52074 Aachen, 
      Germany.
FAU - Schiefer, Johannes
AU  - Schiefer J
FAU - Sass, Christian
AU  - Sass C
FAU - Mey, Jorg
AU  - Mey J
FAU - Brook, Gary
AU  - Brook G
FAU - Kruttgen, Alexander
AU  - Kruttgen A
FAU - Schlangen, Christiane
AU  - Schlangen C
FAU - Bernreuther, Christian
AU  - Bernreuther C
FAU - Schachner, Melitta
AU  - Schachner M
FAU - Dihne, Marcel
AU  - Dihne M
FAU - Kosinski, Christoph M
AU  - Kosinski CM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060930
PL  - Germany
TA  - Exp Brain Res
JT  - Experimental brain research
JID - 0043312
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neurotoxins)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Brain Tissue Transplantation/*methods
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Culture Techniques/methods
MH  - Cell Survival/physiology
MH  - Cells, Cultured
MH  - Corpus Striatum/cytology/physiology/transplantation
MH  - Denervation
MH  - Disease Models, Animal
MH  - Female
MH  - Gliosis/physiopathology/prevention & control
MH  - Graft Survival/*physiology
MH  - Green Fluorescent Proteins/genetics
MH  - Huntington Disease/*therapy
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neurons/cytology/*physiology
MH  - Neurotoxins
MH  - Spheroids, Cellular/cytology/physiology/transplantation
MH  - Stem Cell Transplantation/*methods
MH  - Stem Cells/cytology/*physiology
MH  - Time Factors
EDAT- 2006/10/03 09:00
MHDA- 2007/08/01 09:00
CRDT- 2006/10/03 09:00
PHST- 2006/04/01 00:00 [received]
PHST- 2006/08/24 00:00 [accepted]
PHST- 2006/10/03 09:00 [pubmed]
PHST- 2007/08/01 09:00 [medline]
PHST- 2006/10/03 09:00 [entrez]
AID - 10.1007/s00221-006-0689-y [doi]
PST - ppublish
SO  - Exp Brain Res. 2007 Mar;177(4):458-70. doi: 10.1007/s00221-006-0689-y. Epub 2006 
      Sep 30.