Peer-Reviewed Journal Details
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Stender, S;Murphy, M;O'Brien, T;Stengaard, C;Ulrich-Vinther, M;Soballe, K;Barry, F
2007
January
European Cells & Materials
Adeno-associated viral vector transduction of human mesenchymal stem cells
Published
WOS: 59 ()
Optional Fields
MARROW STROMAL CELLS BONE-MARROW GENE-THERAPY CELLULAR-DIFFERENTIATION VIRUS TRANSDUCTION CARTILAGE DEFECTS IN-VIVO REPAIR OSTEOARTHRITIS MEMBRANE
13
93
99
Mesenchymal stem cells ( MSCs) have received considerable attention in the emerging field of regenerative medicine. One aspect of MSC research focuses on genetically modifying the cells with the aim of enhancing their regenerative potential. Adeno-associated virus ( AAV) holds promise as a vector for human gene therapy, primarily due to its lack of pathogenicity and low risk of insertional mutagenesis. However, the existing data pertaining to AAV transduction of MSCs is limited.The objective of this work was to examine the efficiency and kinetics of in vitro transduction using AAV serotype 2 in human MSCs and to assess whether AAV transduction affects MSC multipotentiality. The results indicated that human MSCs could indeed be transiently transduced in vitro by the AAV2 vector with efficiencies of up to 65%. The percentage of GFP-positive cells peaked at 4 days post-transduction and declined rapidly towards 0% after day 8. The level of transgene expression in the GFP-positive population increased 4-fold over a 10,000 fold viral dose increase. This dose-response contrasted with the 200-fold increase observed in similarly transduced 293-cells, indicating a relatively restricted transgene expression in MSCs following AAV mediated gene delivery. Importantly, transduced MSCs retained multipotential activity comparable to untransduced controls.
1473-2262
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