Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice.
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 were subsequently given transplants of either primary murine brain-derived ECs (MBECs) or fetal blood-derived ECs (FBECs). Mice that received a transplant 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 with controls. MBEC transplantation also facilitated the recovery of circulating white blood cell and platelet counts following radiation exposure. Remarkably, 57% of mice that received a transplant 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 with controls, although these mice did not survive in the long term. These data suggest that reestablishment of endothelial cell activity can improve the hematopoietic recovery and survival of irradiated mice.
Chute
John P
JP
Division of Cellular Therapy, Duke University Medical Center, Durham, NC 27710, USA. john.chute@duke.edu
Muramoto
Garrett G
GG
Salter
Alice B
AB
Meadows
Sarah K
SK
Rickman
Dennis W
DW
Chen
Benny
B
Himburg
Heather A
HA
Chao
Nelson J
NJ
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D017690:Cell Transplantation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D006410:Hematopoiesis / Q000528:radiation effects; D051379:Mice; D013234:Stem Cells / Q000166:cytology; D015996:Survival Rate
D016207:Cytokines