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dc.contributor.authorBaxter, Melissa A
dc.contributor.authorWynn, Robert F
dc.contributor.authorDeakin, Jon A
dc.contributor.authorBellantuono, Ilaria
dc.contributor.authorEdington, Kirsten G
dc.contributor.authorCooper, Alan
dc.contributor.authorBesley, Guy T N
dc.contributor.authorChurch, Heather J
dc.contributor.authorWraith, J Ed
dc.contributor.authorCarr, Trevor F
dc.contributor.authorFairbairn, Leslie J
dc.date.accessioned2009-10-12T11:51:18Z
dc.date.available2009-10-12T11:51:18Z
dc.date.issued2002-03-01
dc.identifier.citationRetrovirally mediated correction of bone marrow-derived mesenchymal stem cells from patients with mucopolysaccharidosis type I. 2002, 99 (5):1857-9 Blooden
dc.identifier.issn0006-4971
dc.identifier.pmid11861306
dc.identifier.doihttp://dx.doi.org/10.1182/blood.V99.5.1857
dc.identifier.urihttp://hdl.handle.net/10541/84055
dc.description.abstractWe have investigated the utility of bone marrow-derived mesenchymal stem cells (MSCs) as targets for gene therapy of the autosomal recessive disorder mucopolysaccharidosis type IH (MPS-IH, Hurler syndrome). Cultures of MSCs were initially exposed to a green fluorescent protein-expressing retrovirus. Green fluorescent protein-positive cells maintained their proliferative and differentiation capacity. Next we used a vector encoding alpha-L-iduronidase (IDUA), the enzyme that is defective in MPS-IH. Following transduction, MPS-IH MSCs expressed high levels of IDUA and secreted supernormal levels of this enzyme into the extracellular medium. Exogenous IDUA expression led to a normalization of glycosaminoglycan storage in MPS-IH cells, as evidenced by a dramatic decrease in the amount of (35)SO(4) sequestered within the heparan sulfate and dermatan sulfate compartments of these cells. Finally, gene-modified MSCs were able to cross-correct the enzyme defect in untransduced MPS-IH fibroblasts via protein transfer.
dc.language.isoenen
dc.subject.meshAdolescent
dc.subject.meshBone Marrow Cells
dc.subject.meshCell Culture Techniques
dc.subject.meshChild
dc.subject.meshChild, Preschool
dc.subject.meshCulture Media, Conditioned
dc.subject.meshGene Therapy
dc.subject.meshHumans
dc.subject.meshIduronidase
dc.subject.meshInfant
dc.subject.meshInfant, Newborn
dc.subject.meshMesoderm
dc.subject.meshMucopolysaccharidosis I
dc.subject.meshRetroviridae
dc.subject.meshStem Cells
dc.subject.meshTransduction, Genetic
dc.titleRetrovirally mediated correction of bone marrow-derived mesenchymal stem cells from patients with mucopolysaccharidosis type I.en
dc.typeArticleen
dc.contributor.departmentDepartment of Haematology, Royal Manchester Children's Hospital, United Kingdom.en
dc.identifier.journalBlooden
html.description.abstractWe have investigated the utility of bone marrow-derived mesenchymal stem cells (MSCs) as targets for gene therapy of the autosomal recessive disorder mucopolysaccharidosis type IH (MPS-IH, Hurler syndrome). Cultures of MSCs were initially exposed to a green fluorescent protein-expressing retrovirus. Green fluorescent protein-positive cells maintained their proliferative and differentiation capacity. Next we used a vector encoding alpha-L-iduronidase (IDUA), the enzyme that is defective in MPS-IH. Following transduction, MPS-IH MSCs expressed high levels of IDUA and secreted supernormal levels of this enzyme into the extracellular medium. Exogenous IDUA expression led to a normalization of glycosaminoglycan storage in MPS-IH cells, as evidenced by a dramatic decrease in the amount of (35)SO(4) sequestered within the heparan sulfate and dermatan sulfate compartments of these cells. Finally, gene-modified MSCs were able to cross-correct the enzyme defect in untransduced MPS-IH fibroblasts via protein transfer.


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