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Title: Efficient lentiviral transduction and improved engraftment of human bone marrow mesenchymal cells
Authors: Van Damme, An *
Thorrez, Lieven *
Ma, Ling
Vandenburgh, Herman
Eyckmans, Jeroen
Dell'Accio, Francesco
De Bari, Cosimo
Luyten, Frank
Lillicrap, David
Collen, Desire
Vandendriessche, Thierry
Chuah, Marinee # ×
Issue Date: Apr-2006
Publisher: AlphaMed Press
Series Title: Stem Cells vol:24 issue:4 pages:896-907
Abstract: Human bone marrow (BM) mesenchymal stem/progenitor cells are potentially attractive targets for ex vivo gene therapy. The potential of lentiviral vectors for transducing BM mesenchymal cells was examined using a self-inactivating vector that expressed the green fluorescent protein (GFP) from an internal cytomegalovirus (CMV) promoter. This vector was compared with oncoretroviral vectors expressing GFP from the CMV promoter or a modified long-terminal repeat that had been optimized for long-term expression in stem cells. The percentage of GFP-positive cells was consistently higher following lentiviral versus oncoretroviral transduction, consistent with increased GFP mRNA levels and increased gene transfer efficiency measured by polymerase chain reaction and Southern blot analysis. In vitro GFP and FVIII expression lasted for several months post-transduction, although expression slowly declined. The transduced cells retained their stem/progenitor cell properties since they were still capable of differentiating along adipogenic and osteogenic lineages in vitro while maintaining high GFP and FVIII expression levels. Implantation of lentivirally transduced human BM mesenchymal cells using collagen scaffolds into immunodeficient mice resulted in efficient engraftment of gene-engineered cells and long-term transgene expression in vivo. These biocompatible BM mesenchymal implants represent a reversible, safe, and versatile protein delivery approach because they can be retrieved in the event of an unexpected adverse reaction or when expression of the protein of interest is no longer required. In conclusion, efficient gene delivery with lentiviral vectors in conjunction with the use of bioengineered reversible scaffolds improves the therapeutic prospects of this novel approach for gene therapy, protein delivery, or tissue engineering.
URI: 
ISSN: 1066-5099
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Rheumatology Section (-)
Hematology Section (-)
Molecular and Vascular Biology
Division of Geology
ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
* (joint) first author
× corresponding author
# (joint) last author

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