ABROGATION OF RADIATION-INJURY TO HUMAN HEMATOPOIETIC STEM-CELLS WITHTUMOR-NECROSIS-FACTOR-ALPHA

Ionizing radiation kills hematopoietic stem and progenitor cells. Howe ver, several cytokines, including tumor necrosis factor-alpha (TNF-alp ha), protect the murine hematopoietic system if they are introduced be fore or immediately after irradiation. We examined the in vitro capaci ty of TNF-alpha to protect human hematopoietic stem cells and early pr ogenitor cells from x-ray-induced death. Human CD34(+) cells obtained from normal bone marrow were highly enriched for stem and progenitor c ells. Pulse exposure of these cells to human TNF-alpha during the firs t hour immediately after x irradiation (doses of 0.45 Gy to 9 Gy) sign ificantly improved further survival of true hematopoietic stem cells a nd early progenitors and the ability of CD34(+) cells to produce matur e hematopoietic cells in liquid culture with hematopoietic growth fact ors. The radioprotective effect of TNF-alpha was stronger at lower dos es, when complete restoration of hematopoiesis was often observed. In contrast, the radioprotective effect of TNF-alpha was moderate at high er doses, with neither complete restoration of the number of stem and progenitor cells nor the production of mature cells. Our data suggest that TNF-alpha can protect human hematopoietic stem and early progenit or cells from ionizing radiation.