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

Blood. 2002 Mar 1;99(5):1857-9. doi: 10.1182/blood.v99.5.1857.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bone Marrow Cells / pathology
  • Cell Culture Techniques
  • Child
  • Child, Preschool
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / pharmacology
  • Genetic Therapy / methods
  • Humans
  • Iduronidase / genetics
  • Iduronidase / metabolism
  • Iduronidase / pharmacology
  • Infant
  • Infant, Newborn
  • Mesoderm / drug effects
  • Mesoderm / pathology*
  • Mucopolysaccharidosis I / pathology
  • Mucopolysaccharidosis I / therapy*
  • Retroviridae / genetics*
  • Stem Cells / drug effects*
  • Stem Cells / pathology
  • Transduction, Genetic

Substances

  • Culture Media, Conditioned
  • Iduronidase