Retrovirally mediated correction of bone marrow-derived mesenchymal stem cells from patients with mucopolysaccharidosis type I.

2.50
Hdl Handle:
http://hdl.handle.net/10541/84055
Title:
Retrovirally mediated correction of bone marrow-derived mesenchymal stem cells from patients with mucopolysaccharidosis type I.
Authors:
Baxter, Melissa A; Wynn, Robert F; Deakin, Jon A; Bellantuono, Ilaria; Edington, Kirsten G; Cooper, Alan; Besley, Guy T N; Church, Heather J; Wraith, J Ed; Carr, Trevor F; Fairbairn, Leslie J
Abstract:
We 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.
Affiliation:
Department of Haematology, Royal Manchester Children's Hospital, United Kingdom.
Citation:
Retrovirally mediated correction of bone marrow-derived mesenchymal stem cells from patients with mucopolysaccharidosis type I. 2002, 99 (5):1857-9 Blood
Journal:
Blood
Issue Date:
1-Mar-2002
URI:
http://hdl.handle.net/10541/84055
DOI:
http://dx.doi.org/10.1182/blood.V99.5.1857
PubMed ID:
11861306
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBaxter, Melissa Aen
dc.contributor.authorWynn, Robert Fen
dc.contributor.authorDeakin, Jon Aen
dc.contributor.authorBellantuono, Ilariaen
dc.contributor.authorEdington, Kirsten Gen
dc.contributor.authorCooper, Alanen
dc.contributor.authorBesley, Guy T Nen
dc.contributor.authorChurch, Heather Jen
dc.contributor.authorWraith, J Eden
dc.contributor.authorCarr, Trevor Fen
dc.contributor.authorFairbairn, Leslie Jen
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.en
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

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