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Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3710-3715
Hematopoietic stem cells with controllable tEpoR transgenes have
a competitive advantage in bone marrow transplantation
Suzanne Kirby,
William Walton, and
Oliver Smithies
From the Department of Medicine, the Lineberger Comprehensive Cancer
Center, and the Department of Pathology, University of North Carolina,
Chapel Hill, NC.
In a previous study, it was found that a truncated erythropoietin
receptor transgene (tEpoR tg) enables multilineage hematopoietic progenitor amplification after treatment with erythropoietin (epo) in
vitro and in vivo. This study used competitive bone marrow (BM)
repopulation to show that tEpoR tg facilitates transplantation by
hematopoietic stem cells (HSC). Individual multilineage colonies, committed myeloid progenitor colonies, and lymphoid colonies (pre-B colony-forming units) were grown from the marrow of animals 6 months
after they received a 50/50 mixture of transgene and wild-type BM
cells. In epo-treated recipients, the transgene-bearing cells significantly outcompeted the wild-type cells (84%-100% versus 16%-0%, respectively). In recipients treated with phosphate-buffered saline, the repopulation was minimally different from the donor mixture
(49%-64% transgene versus 51%-36% wild-type). The epo-induced repopulation advantage is maintained in secondary transplants. In
addition, neither accelerated HSC depletion nor uncontrollable proliferation occurred during epo-stimulated serial transplants of
transgene-containing BM. Thus, the tEpoR tg functions in a benign
fashion in HSC and allows for a significant and controllable repopulation advantage in vivo without excessive HSC depletion relative
to wild-type BM.
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