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Transgenic reporter mice as tools for studies of transplantability and connectivity of dopamine neuron precursors in fetal tissue grafts

Thompson, Lachlan H. and Björklund, Anders LU (2009) In Progress in Brain Research 175. p.53-79
Abstract
Cell therapy for Parkinson's disease (PD) is based on the idea that new midbrain dopamine (mDA) neurons, implanted directly into the brain of the patient, can structurally and functionally replace those lost to the disease. Clinical trials have provided proof-of-principle that the grafted mDA neurons can survive and function after implantation in order to provide sustained improvement in motor function for some patients. Nonetheless, there are a number of issues limiting the application of this approach as mainstream therapy, including: the use of human fetal tissue as the only safe and reliable source of transplantable mDA neurons, and variability in the therapeutic outcome. Here we review recent progress in this area from investigations... (More)
Cell therapy for Parkinson's disease (PD) is based on the idea that new midbrain dopamine (mDA) neurons, implanted directly into the brain of the patient, can structurally and functionally replace those lost to the disease. Clinical trials have provided proof-of-principle that the grafted mDA neurons can survive and function after implantation in order to provide sustained improvement in motor function for some patients. Nonetheless, there are a number of issues limiting the application of this approach as mainstream therapy, including: the use of human fetal tissue as the only safe and reliable source of transplantable mDA neurons, and variability in the therapeutic outcome. Here we review recent progress in this area from investigations using rodent models of PD, paying particular attention to the use of transgenic reporter mice as tools for neural transplantation studies. Cell type-specific expression of reporter genes, such as green fluorescent protein, affords valuable technical advantages in transplantation experiments, such as the ability to selectively isolate specific cell fractions from mixed populations prior to grafting, and the unambiguous visualization of graft-derived dopamine neuron fiber patterns after transplantation. The results from these investigations have given new insights into the transplantability of mDA precursors as well as their connectivity after grafting and have interesting implications for the development of stem cell based approaches for the treatment of PD. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
mesencephalon, ventral, Parkinson's disease, transplantation, regeneration, GFP, cell sorting, cell therapy
in
Progress in Brain Research
volume
175
pages
53 - 79
publisher
Elsevier
external identifiers
  • wos:000280608000006
  • scopus:67849130967
ISSN
1875-7855
DOI
10.1016/S0079-6123(09)17505-2
language
English
LU publication?
yes
id
6a8cac6d-2af4-4f09-8e35-d3a28ea40d88 (old id 1672087)
date added to LUP
2010-09-21 12:23:40
date last changed
2017-10-01 04:26:55
@article{6a8cac6d-2af4-4f09-8e35-d3a28ea40d88,
  abstract     = {Cell therapy for Parkinson's disease (PD) is based on the idea that new midbrain dopamine (mDA) neurons, implanted directly into the brain of the patient, can structurally and functionally replace those lost to the disease. Clinical trials have provided proof-of-principle that the grafted mDA neurons can survive and function after implantation in order to provide sustained improvement in motor function for some patients. Nonetheless, there are a number of issues limiting the application of this approach as mainstream therapy, including: the use of human fetal tissue as the only safe and reliable source of transplantable mDA neurons, and variability in the therapeutic outcome. Here we review recent progress in this area from investigations using rodent models of PD, paying particular attention to the use of transgenic reporter mice as tools for neural transplantation studies. Cell type-specific expression of reporter genes, such as green fluorescent protein, affords valuable technical advantages in transplantation experiments, such as the ability to selectively isolate specific cell fractions from mixed populations prior to grafting, and the unambiguous visualization of graft-derived dopamine neuron fiber patterns after transplantation. The results from these investigations have given new insights into the transplantability of mDA precursors as well as their connectivity after grafting and have interesting implications for the development of stem cell based approaches for the treatment of PD.},
  author       = {Thompson, Lachlan H. and Björklund, Anders},
  issn         = {1875-7855},
  keyword      = {mesencephalon,ventral,Parkinson's disease,transplantation,regeneration,GFP,cell sorting,cell therapy},
  language     = {eng},
  pages        = {53--79},
  publisher    = {Elsevier},
  series       = {Progress in Brain Research},
  title        = {Transgenic reporter mice as tools for studies of transplantability and connectivity of dopamine neuron precursors in fetal tissue grafts},
  url          = {http://dx.doi.org/10.1016/S0079-6123(09)17505-2},
  volume       = {175},
  year         = {2009},
}