Abrogation of radiation injury to human hematopoietic stem cells with tumor necrosis factor-alpha.

Abstract

Ionizing radiation kills hematopoietic stem and progenitor cells. However, several cytokines, including tumor necrosis factor-alpha (TNF-alpha), protect the murine hematopoietic system if they are introduced before or immediately after irradiation. We examined the in vitro capacity of TNF-alpha to protect human hematopoietic stem cells and early progenitor cells from x-ray-induced death. Human CD34+ cells obtained from normal bone marrow were highly enriched for stem and progenitor cells. Pulse exposure of these cells to human TNF-alpha during the first hour immediately after x irradiation (doses of 0.45 Gy to 9 Gy) significantly improved further survival of true hematopoietic stem cells and early progenitors and the ability of CD34+ cells to produce mature hematopoietic cells in liquid culture with hematopoietic growth factors. The radioprotective effect of TNF-alpha was stronger at lower doses, when complete restoration of hematopoiesis was often observed. In contrast, the radioprotective effect of TNF-alpha was moderate at higher 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 progenitor cells from ionizing radiation.