TY - JOUR
T1 - Mobilization and transduction of peripheral blood progenitor cells in patients with mucopolysaccharidosis I
AU - Hubel, Allison
AU - Stroncek, David
AU - Pan, Dao
AU - Whitley, Chester B
AU - Mc Cullough, Jeffrey
PY - 1998/12
Y1 - 1998/12
N2 - 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.
AB - 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.
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U2 - 10.1089/scd.1.1998.7.505
DO - 10.1089/scd.1.1998.7.505
M3 - Article
C2 - 9919944
AN - SCOPUS:0032410725
SN - 1525-8165
VL - 7
SP - 505
EP - 514
JO - Journal of Hematotherapy and Stem Cell Research
JF - Journal of Hematotherapy and Stem Cell Research
IS - 6
ER -