| First Author | Kirby SL | Year | 1996 |
| Journal | Proc Natl Acad Sci U S A | Volume | 93 |
| Issue | 18 | Pages | 9402-7 |
| PubMed ID | 8790342 | Mgi Jnum | J:81859 |
| Mgi Id | MGI:2450099 | Doi | 10.1073/pnas.93.18.9402 |
| Citation | Kirby SL, et al. (1996) Proliferation of multipotent hematopoietic cells controlled by a truncated erythropoietin receptor transgene. Proc Natl Acad Sci U S A 93(18):9402-7 |
| abstractText | The long-term efficacy of gene therapy using bone marrow transplantation requires the engraftment of genetically altered totipotent hematopoietic stem cells (THSCs). Ex vivo expansion of corrected THSCs is one way to increase the efficiency of the procedure. Similarly, selective in vivo expansion of the therapeutic THSCs rather than the endogenous THSCs could favor the transplant. To test whether a conferred proliferative advantage gene can facilitate the in vitro and in vivo expansion of hematopoietic stem cells, we have generated transgenic mice expressing a truncated receptor for the growth factor erythropoietin. These mice are phenotypically normal, but when treated in vivo with exogenous erythropoietin they exhibit a marked increase in multipotent, clonogenic hematopoietic cells [colony-forming units in the spleen (CFU-S) and CFUs that give rise to granulocytes, erythroid cells, macrophages, and megakaryocytes within the same colony (CFU-GEMM)] in comparison with the wild-type mice. In addition, long-term in vitro culture of tEpoR transgenic bone marrow in the presence of erythropoietin induces exponential expansion of trilineage hematopoietic stem cells not seen with wild-type bone marrow. Thus, the truncated erythropoietin receptor gene shows promise as a means for obtaining cytokine-inducible hematopoietic stem cell proliferation to facilitate the direct targeting of THSCs and to provide a competitive repopulation advantage for transplanted therapeutic stem cells. |
