Acute Radiation Syndrome (ARS) is a syndrome involving damage to multiple organs caused by exposure to a high dose of ionizing radiation over a short period of time; even low doses of radiation damage the radiosensitive hematopoietic system (causing H-ARS). PLacenta eXpanded (PLX)-R18 is a 3D-expanded placenta-derived stromal cell product designated for the treatment of hematological disorders. In study presented here, we assessed the potential effect of PLX-R18 treatment on H-ARS. PLX-R18 cells were administered intramuscularly to C3H/HeN and C57BL/6 mice, 1 and 5 days after (LD70/30) total body irradiation. Weight, survival, peripheral blood and BM cellularity were monitored at several time points up to 23 days. PLX‑R18 treatment significantly increased survival after irradiation and rescued radio-induced weight loss. In addition, PLX-R18 treatment significantly increased the number of colony forming hematopoietic progenitors in the BM and raised peripheral blood cellularity to values near those of un-irradiated control values. PLX-R18 cells responded to radiation-induced hematopoietic failure by transiently secreting haematopoiesis related proteins to enhance reconstitution of the hematopoietic system.