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Improving the survival of grafted dopaminergic neurons: a review over current approaches

Brundin, Patrik LU ; Karlsson, Jenny LU ; Emgård-Mattson, Mia LU ; Schierle, Gabriele LU ; Hansson, Oskar LU ; Petersén, Åsa LU and Castilho, Roger F (2000) In Cell Transplantation 9(2). p.179-195
Abstract
Neural transplantation is developing into a therapeutic alternative in Parkinson's disease. A major limiting factor is that only 3-20% of grafted dopamine neurons survive the procedure. Recent advances regarding how and when the neurons die indicate that events preceding actual tissue implantation and during the first week thereafter are crucial, and that apoptosis plays a pivotal role. Triggers that may initiate neuronal death in grafts include donor tissue hypoxia and hypoglycemia, mechanical trauma, free radicals, growth factor deprivation, and excessive extracellular concentrations of excitatory amino acids in the host brain. Four distinct phases during grafting that can involve cell death have been identified: retrieval of the embryo;... (More)
Neural transplantation is developing into a therapeutic alternative in Parkinson's disease. A major limiting factor is that only 3-20% of grafted dopamine neurons survive the procedure. Recent advances regarding how and when the neurons die indicate that events preceding actual tissue implantation and during the first week thereafter are crucial, and that apoptosis plays a pivotal role. Triggers that may initiate neuronal death in grafts include donor tissue hypoxia and hypoglycemia, mechanical trauma, free radicals, growth factor deprivation, and excessive extracellular concentrations of excitatory amino acids in the host brain. Four distinct phases during grafting that can involve cell death have been identified: retrieval of the embryo; dissection and preparation of the donor tissue; implantation procedure followed by the immediate period after graft injection; and later stages of graft maturation. During these phases, cell death processes involving free radicals and caspase activation (leading to apoptosis) may be triggered, possibly involving an increase in intracellular calcium. We review different approaches that reduce cell death and increase survival of grafted neurons, typically by a factor of 2-4. For example, changes in transplantation procedure such as improved media and implantation technique can be beneficial. Calcium channel antagonists such as nimodipine and flunarizine improve nigral graft survival. Agents that counteract oxidative stress and its consequences, such as superoxide dismutase overexpression, and lazaroids can significantly increase the survival of transplanted dopamine neurons. Also, the inhibition of apoptosis by a caspase inhibitor has marked positive effects. Finally, basic fibroblast growth factor and members of the transforming growth factor-beta superfamily, such as glial cell line-derived neurotrophic factor, significantly improve the outcome of nigral transplants. These recent advances provide hope for improved survival of transplanted neurons in patients with Parkinson's disease, reducing the need for human embryonic donor tissue and increasing the likelihood of a successful outcome. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Transplantation, Parkinson's disease, Neuroprotection, Growth factor, Cell death
in
Cell Transplantation
volume
9
issue
2
pages
179 - 195
publisher
Cognizant Communication Corporation
external identifiers
  • pmid:10811392
  • scopus:0034065380
ISSN
1555-3892
language
English
LU publication?
yes
id
4240b5f0-d3ed-41e6-bde9-992e6667b28c (old id 1117118)
date added to LUP
2008-07-02 16:39:40
date last changed
2017-11-05 04:43:02
@article{4240b5f0-d3ed-41e6-bde9-992e6667b28c,
  abstract     = {Neural transplantation is developing into a therapeutic alternative in Parkinson's disease. A major limiting factor is that only 3-20% of grafted dopamine neurons survive the procedure. Recent advances regarding how and when the neurons die indicate that events preceding actual tissue implantation and during the first week thereafter are crucial, and that apoptosis plays a pivotal role. Triggers that may initiate neuronal death in grafts include donor tissue hypoxia and hypoglycemia, mechanical trauma, free radicals, growth factor deprivation, and excessive extracellular concentrations of excitatory amino acids in the host brain. Four distinct phases during grafting that can involve cell death have been identified: retrieval of the embryo; dissection and preparation of the donor tissue; implantation procedure followed by the immediate period after graft injection; and later stages of graft maturation. During these phases, cell death processes involving free radicals and caspase activation (leading to apoptosis) may be triggered, possibly involving an increase in intracellular calcium. We review different approaches that reduce cell death and increase survival of grafted neurons, typically by a factor of 2-4. For example, changes in transplantation procedure such as improved media and implantation technique can be beneficial. Calcium channel antagonists such as nimodipine and flunarizine improve nigral graft survival. Agents that counteract oxidative stress and its consequences, such as superoxide dismutase overexpression, and lazaroids can significantly increase the survival of transplanted dopamine neurons. Also, the inhibition of apoptosis by a caspase inhibitor has marked positive effects. Finally, basic fibroblast growth factor and members of the transforming growth factor-beta superfamily, such as glial cell line-derived neurotrophic factor, significantly improve the outcome of nigral transplants. These recent advances provide hope for improved survival of transplanted neurons in patients with Parkinson's disease, reducing the need for human embryonic donor tissue and increasing the likelihood of a successful outcome.},
  author       = {Brundin, Patrik and Karlsson, Jenny and Emgård-Mattson, Mia and Schierle, Gabriele and Hansson, Oskar and Petersén, Åsa and Castilho, Roger F},
  issn         = {1555-3892},
  keyword      = {Transplantation,Parkinson's disease,Neuroprotection,Growth factor,Cell death},
  language     = {eng},
  number       = {2},
  pages        = {179--195},
  publisher    = {Cognizant Communication Corporation},
  series       = {Cell Transplantation},
  title        = {Improving the survival of grafted dopaminergic neurons: a review over current approaches},
  volume       = {9},
  year         = {2000},
}