Lv. Karkanitsa et al., ABROGATION OF RADIATION-INJURY TO HUMAN HEMATOPOIETIC STEM-CELLS WITHTUMOR-NECROSIS-FACTOR-ALPHA, Stem cells, 15, 1997, pp. 95-102
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.