Hematopoietic stem cells with controllable tEpoR transgenes have a competitive advantage in bone marrow transplantation

In a previous study, it was found that a truncated erythropoietin receptor transgene (tEpoR tg) enables multilineage hematopoietic progenitor amplific ation 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 m ultilineage colonies, committed myeloid progenitor colonies, and lymphoid c olonies (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 wildtype cells (84%-100% versus 16%-0%, respectively). In recipients treated with phosphate-buffered saline, the repopulation was min imally different from the donor mixture (49%-64% transgene versus 51%-36% w ild-type). The epo-induced repopulation advantage is maintained in secondar y transplants. In addition, neither accelerated HSC depletion nor uncontrol lable proliferation occurred during epo-stimulated serial transplants of tr ansgene-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. (C) 2000 by The American Society of Hematology.