Stable gene expression by self-complementary adeno-associated viruses in human MSCs.
Genetically modified mesenchymal stem cells (MSCs) are potentially valuable tools for the novel treatment of human illnesses. Here, we investigated whether gene transfers by self-complementary adeno-associated viruses (scAAV) lead to promising genetic modification in human bone marrow and umbilical cord blood MSCs. Of the various scAAVs, scAAV2, and scAAV5 effectively and safely expressed transgenes in both hMSCs. Transduction efficiency with scAAV2 at 1000 multiplicity of infection was 66.3+/-9.4% and 67.6+/-6.7% in bone marrow and umbilical cord blood MSCs, respectively. A co-infection study showed that the distinct scAAV2 and scAAV5 can effectively express different transgenes in the same hMSC. hMSCs transduced by scAAVs showed long-term gene expression for three months in rat brains. Genetic modification by scAAVs did not affect osteogenic differentiation of hMSCs. Therefore, the present study strongly supports the promising potential of scAAVs as a technical platform for safe, long-term transgene expression in hMSCs.
Kim
Sung Jin
SJ
Department of Microbiology, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Lee
Won Il
WI
Heo
Hwon
H
Shin
Ohkyu
O
Kwon
Yunhee Kim
YK
Lee
Heuiran
H
D015703:Antigens, CD / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology; D010006:Osteoblasts / Q000502:physiology; D019076:Transgenes
D015703:Antigens, CD; D049452:Green Fluorescent Proteins