Mobilization and transduction of peripheral blood progenitor cells in patients with mucopolysaccharidosis I

Allison Hubel, David Stroncek, Dao Pan, Chester B Whitley, Jeffrey Mc Cullough

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Mucopolysaccharidosis type I (MPS I) results from a deficiency of α-L-iduronidase enzyme (IDUA), an enzyme responsible for the catabolism of glycosaminoglycans. Genetically modified progenitor cells may permit a therapeutic effect similar to that obtained from allogeneic BMT without the associated risks. To that end, CD34+ peripheral blood hematopoietic progenitor cells from patients with MPS I were mobilized using G-CSF, collected by apheresis, and enriched using avidin-biotin separation techniques. These cells were cultured in a hollow fiber bioreactor and transduced with a retroviral vector (LP1CD) containing the cDNA for human IDUA and a murine dihydrofolate reductase (DHFR) enzyme. Approximately 4%-16% of the colonies expressed methotrexate drug resistance. Expression of the IDUA enzyme in the progenitor cells was initially high and declined after approximately 10 days of culture. These results indicate that PBPC from patients with MPS I can be mobilized, isolated, enriched, and transduced with a therapeutic gene.

Original languageEnglish (US)
Pages (from-to)505-514
Number of pages10
JournalJournal of Hematotherapy and Stem Cell Research
Volume7
Issue number6
DOIs
StatePublished - Dec 1998

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