Retrovirally mediated correction of bone marrow-derived mesenchymal stem cells from patients with mucopolysaccharidosis type I
| Autor: | Trevor F. Carr, Melissa A. Baxter, Heather J. Church, Jonathan A. Deakin, Ilaria Bellantuono, Robert Wynn, Leslie J. Fairbairn, Kirsten G. Edington, J. Ed Wraith, G. T. N. Besley, Alan Cooper |
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| Rok vydání: | 2002 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities medicine.medical_specialty Adolescent Mucopolysaccharidosis I Immunology Cell Culture Techniques Bone Marrow Cells Biology Biochemistry Dermatan sulfate Mesoderm chemistry.chemical_compound Mucopolysaccharidosis type I Iduronidase Transduction Genetic Internal medicine medicine Humans skin and connective tissue diseases Hurler syndrome Child Stem Cells Mesenchymal stem cell Infant Newborn Infant Cell Biology Hematology Genetic Therapy medicine.disease Cell biology Endocrinology medicine.anatomical_structure Retroviridae chemistry Cell culture Child Preschool Culture Media Conditioned Bone marrow Stem cell |
| Zdroj: | Blood. 99(5) |
| ISSN: | 0006-4971 |
| Popis: | 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 α-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 35SO4sequestered 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. |
| Databáze: | OpenAIRE |
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