Document Detail

A novel approach to ex vivo gene therapy for familial hypercholesterolemia using human amniotic epithelial cells as a transgene carrier.
MedLine Citation:
PMID:  11453536     Owner:  NLM     Status:  MEDLINE    
This study has demonstrated the potential of human amniotic epithelial cells (HAEC) as a transgene carrier to treat patients with familial hypercholesterolemia (FH). One approach to liver-directed gene therapy is represented by transplantation of autologous hepatocytes that have been genetically modified in vitro. However, the hepatocytes must be isolated from surgically resected tissue and it is difficult to expand the hepatocytes in culture. In contrast, the advantages for using HAEC are the higher availability and the nonimmunogenicity after allotransplantation. Our strategy involved isolating HAEC from an amnion, transducing a human low-density lipoprotein receptor (LDLR) gene into these cells with a recombinant adenovirus, and transplanting the genetically modified cells into the liver of an animal model of FH. Each animal, treated with the LDLR-transduced HAEC, exhibited a substantial decrease in serum cholesterol with an eventual return to pretreatment level. Moreover, the transplanted HAEC migrated out of the sinusoids into the hepatic parenchyma and expressed the LDLRs until at least 20 days after transplantation. However, the transplanted HAEC markedly decreased in number after 10 days post-transplant with an increase of inflammatory cells. The temporary nature of the metabolic improvement may be associated with xenograft rejection and transient function of the adenoviral vector.
S Takahashi; K Ohsugi; T Yamamoto; M Shiomi; N Sakuragawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Tohoku journal of experimental medicine     Volume:  193     ISSN:  0040-8727     ISO Abbreviation:  Tohoku J. Exp. Med.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-07-16     Completed Date:  2001-12-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0417355     Medline TA:  Tohoku J Exp Med     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  279-92     Citation Subset:  IM    
Department of Inherited Metabolic Disease, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
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MeSH Terms
Adenoviruses, Human / genetics
Amnion / cytology*
Cell Movement
Cell Transplantation*
Cells, Cultured / transplantation
Cholesterol / blood
Defective Viruses / genetics
Disease Models, Animal
Epithelial Cells / transplantation
Gene Therapy / methods*
Genetic Vectors / genetics
Graft Rejection / immunology
Hyperlipoproteinemia Type II / blood,  genetics,  therapy*
Liver / pathology
Receptors, LDL / deficiency,  genetics*
Sequence Deletion
Transplantation, Heterologous / immunology
Transplantation, Heterotopic
Reg. No./Substance:
0/Receptors, LDL; 57-88-5/Cholesterol

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

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