Document Detail


Implantation of human amniotic epithelial cells prevents the degeneration of nigral dopamine neurons in rats with 6-hydroxydopamine lesions.
MedLine Citation:
PMID:  12865158     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We recently found that human amniotic epithelial (HAE) cells secrete biologically active neurotrophins such as brain-derived neurotrophic factor and neurotrophin-3, both of which exhibit trophic activities on dopamine (DA) neurons. The present study explored whether implantation of HAE cells can be a possible means to deliver trophic factors into the brain to prevent the death of DA neurons in a rat model of Parkinson's disease. We first investigated the ability of HAE cells to produce factors capable of promoting DA cell survival in vitro, and then tested whether HAE cell grafts survive and prevent the death of nigral DA neurons in rats with 6-hydroxydopamine lesions. A treatment with conditioned medium derived from HAE cell cultures enhanced the survival of tyrosine hydroxylase (TH)-immunopositive DA cells in serum-free cultures. The conditioned medium also protected the morphological integrity of TH-positive neurons against toxic insult with 6-hydroxydopamine. HAE cells were grafted into the midbrain of immunosuppressed rats. The rats were then subjected to a unilateral nigrostriatal lesion induced by intrastriatal infusions of 6-hydroxydopamine. HAE cell transplants were found to survive without evidence for overgrowth 2 weeks postgrafting. The number of nigral DA cells, detected with either TH-immunohistochemistry or retrograde labelling with fluorogold, was significantly increased in rats given the grafts as compared to that in control animals without the grafts. The results indicate that HAE cells produce diffusible molecules that can enhance the survival of DA neurons. Although the factors that contribute to the currently observed effects remain to be fully determined, implantation of HAE cells could be a viable strategy to counteract the loss of DA neurons in Parkinson's disease.
Authors:
Koji Kakishita; Naoyuki Nakao; Norio Sakuragawa; Toru Itakura
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research     Volume:  980     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-07-16     Completed Date:  2003-11-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  48-56     Citation Subset:  IM    
Affiliation:
Department of Neurological Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amnion / transplantation*
Animals
Cell Culture Techniques
Cell Survival
Dopamine / metabolism*
Epithelial Cells / transplantation*
Female
Fetal Tissue Transplantation*
Humans
Nerve Degeneration / chemically induced,  prevention & control*
Neurons / metabolism,  pathology*
Oxidopamine
Rats
Rats, Sprague-Dawley
Substantia Nigra / metabolism,  pathology*
Sympatholytics
Chemical
Reg. No./Substance:
0/Sympatholytics; 1199-18-4/Oxidopamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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