Simulation of hematopoiesis: implications for the gene therapy of lysosomal enzyme disorders.
Although the hematopoietic stem cell is an attractive target for gene transfer, little is known about its biology in vivo in large animals (including humans). We have studied the in vivo behavior of hematopoietic stem cells in glucose-6-phosphate dehydrogenase heterozygous (female Safari) cats, and demonstrated that clonal instability persists for up to 4.5 years after autologous marrow transplantation. This contrasts with the 2-6 months of clonal disequilibrium reported in comparable murine studies. Our data also suggest that hematopoietic stem cells do not self-renew more than once every 3 weeks. These data may have relevance for strategies to optimize gene therapy in large animals and, by extension, in humans.
Abkowitz
J L
JL
Department of Medicine, University of Washington, Seattle, 98195 (USA).
Persik
M T
MT
Catlin
S N
SN
Guttorp
P
P
D000818:Animals; D002415:Cats; D002454:Cell Differentiation; D003198:Computer Simulation; D015672:Erythroid Precursor Cells / Q000166:cytology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008137:Longitudinal Studies; D016464:Lysosomal Storage Diseases / Q000097:blood / Q000235:genetics / Q000628:therapy; D051379:Mice; D010641:Phenotype; D014182:Transplantation, Autologous
D005954:Glucosephosphate Dehydrogenase