Safe and effective gene transfer by adeno-associated virus of neonatal thymus-derived mesenchymal stromal cells
2011
Lee, W.I. | Khim, M. | Im, I.R. | Shin, O. | Park, J.W. | Choo, S.J. | Yun, T.J. | Kim, S.W. | Lee, H.
Recently, human neonatal thymus-derived mesenchymal stromal cells (nTMSCs) have been recognized as a promising mesenchymal stem cell source for combined cell and gene therapy. While efficient gene transfer is crucial for optimizing therapeutic efficacy, almost no studies have yet reported on the characteristics of nTMSC in terms of genetic modification. The present study investigates and realizes the potential of self-complementary adeno-associated viruses (scAAVs) as an effective transduction tool for nTMSCs. Transduction efficiency (TE), cytotoxicity and functional characteristics were determined in nTMSCs isolated from thymic tissues and transduced with scAAV1-6 and -8 serotypes expressing GFP. Our study confirms MSC-typical characteristics in nTMSCs and additionally, suggests further therapeutic advantages of nTMSCs due to its particularities with lower levels of MHC class I protein and higher levels of CD31 and CD34 expression. Effective transduction by scAAV2 and scAAV5 was evident in the majority of nTMSCs that were GFP-positive at a multiplicity of infection (MOI) of 1000. TE was further improved by higher MOI treatments. Transduced cells also successfully maintained adipocyte and vessel-forming endothelial cell multi-potency and showed no evidence of gene delivery-related cytotoxicity. Collectively, the data strongly suggest that scAAVs are promising technical platforms for safe and effective transgene expression in nTMSCs.
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