Submitted May 19, 2006
Accepted October 29, 2006
Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice
John P Chute*, Garrett G Muramoto, Alice B Salter, Sarah K Meadows, Dennis Rickman, Benny Chen, Heather A Himburg, and Nelson J Chao
Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC
Department of Neurobiology, Duke University Medical Center, Durham, NC
* Corresponding author; email: john.chute{at}duke.edu.
Flk-1+ endothelial progenitors contribute critically to the definitive onset of hematopoiesis during embryogenesis. Recent studies have suggested that adult sources of endothelial cells also possess hematopoietic activity. In this study we sought to determine whether transplantation of primary vascular endothelial cells (ECs) could enhance the hematopoietic recovery and survival of irradiated mice. C57Bl6 mice were exposed to sublethal and lethal doses of irradiation and subsequently transplanted with either primary murine brain-derived ECs (MBECs) or fetal blood-derived ECs (FBECs). Mice transplanted with MBECs alone demonstrated accelerated BM cellular recovery, radioprotection of BM c-kit+sca-1- lin- progenitors and enhanced regeneration of c-kit+sca-1+lin- (KSL) stem/progenitor cells following irradiation compared to controls. MBEC transplantation also facilitated the recovery of circulating white blood cells and platelet counts following radiation exposure. Remarkably, 57% of mice transplanted with MBECs alone survived long-term following 1050 cGy exposure, which was 100% lethal in control mice. FBEC transplantation was also associated with increased survival compared to controls, although these mice did not survive long-term. These data suggest that reestablishment of endothelial cell activity can improve the hematopoietic recovery and survival of irradiated mice.
