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Transduction of human adipose-derived mesenchymal stem cells by recombinant adeno-associated virus vectors.

Abstract
Human adipose-derived stem cells (ASCs) are attractive targets for genetic manipulation and cellular therapies. However, current methods of gene transfer are limited by lack of efficiency, toxicity, or safety concerns. Recombinant adeno-associated virus (rAAV) has been extensively assessed as a gene therapy vector and has an excellent safety profile. This study reports the efficient transduction of well-characterized, homogeneous cultures of human ASCs by rAAV serotypes 2, 5, and 6. Transduction with rAAV2 at high multiplicity of infection was associated with reduced cell viability; however, no adverse effect was seen with serotypes 5 and 6. A further increase in transduction efficiency was observed using a rAAV6 Y731F tyrosine capsid mutant. rAAV-transduced ASCs retained their adipogenic potential. Therefore, rAAV serotypes 2, 5, and 6 should be considered the vectors of choice for genetic manipulation of ASCs.
AuthorsMichelle Locke, James E Ussher, Raakhi Mistry, John A Taylor, P Rod Dunbar
JournalTissue engineering. Part C, Methods (Tissue Eng Part C Methods) Vol. 17 Issue 9 Pg. 949-59 (Sep 2011) ISSN: 1937-3392 [Electronic] United States
PMID21563982 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© Mary Ann Liebert, Inc.
Chemical References
  • Biomarkers
  • Tyrosine
Topics
  • Adipogenesis
  • Adipose Tissue (cytology)
  • Adult
  • Biomarkers (metabolism)
  • Capsid (metabolism)
  • Cells, Cultured
  • Dependovirus (genetics)
  • Female
  • Fibroblasts (cytology)
  • Genetic Vectors (genetics)
  • Humans
  • Male
  • Mesenchymal Stromal Cells (cytology, metabolism)
  • Middle Aged
  • Mutation (genetics)
  • Phenotype
  • Recombination, Genetic (genetics)
  • Tissue Donors
  • Transduction, Genetic (methods)
  • Tyrosine (genetics)

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