Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-4-28
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1066-5099
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
896-907
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16339997-Adipogenesis, pubmed-meshheading:16339997-Base Sequence, pubmed-meshheading:16339997-Biomedical Engineering, pubmed-meshheading:16339997-Cell Differentiation, pubmed-meshheading:16339997-Cells, Cultured, pubmed-meshheading:16339997-DNA, pubmed-meshheading:16339997-Factor VIII, pubmed-meshheading:16339997-Gene Therapy, pubmed-meshheading:16339997-Graft Survival, pubmed-meshheading:16339997-Green Fluorescent Proteins, pubmed-meshheading:16339997-Hematopoietic Stem Cell Transplantation, pubmed-meshheading:16339997-Hematopoietic Stem Cells, pubmed-meshheading:16339997-Humans, pubmed-meshheading:16339997-Lentivirus, pubmed-meshheading:16339997-Mesenchymal Stem Cell Transplantation, pubmed-meshheading:16339997-Mesenchymal Stem Cells, pubmed-meshheading:16339997-Osteogenesis, pubmed-meshheading:16339997-RNA, Messenger, pubmed-meshheading:16339997-Recombinant Proteins, pubmed-meshheading:16339997-Transduction, Genetic
pubmed:year
2006
pubmed:articleTitle
Efficient lentiviral transduction and improved engraftment of human bone marrow mesenchymal cells.
pubmed:affiliation
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Herestraat 49, Building O&N1, Leuven B-3000, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't