Raphael Gorodetsky
Hadassah-Hebrew University Medical Center, Israel
Posters & Accepted Abstracts: Gynecol Obstet
Acute radiation syndrome (ARS) is associated with the hematopoietic crisis. It results in life-threatening acute effects to which a very limited arsenal for adequate treatments is available. Only ~10% of female C3H mice survived up to 23 days following 8Gy total body irradiation. We developed a non-matched cell-based therapy for ARS based on the remotely injected pure population of potent fetal-derived human placental stromal cells (f-hPSC). The isolation procedure of the f-hPSC from intact fresh or cryopreserved fetal human placental tissues fragments is based on their selective spontaneous migration to plastic surfaces to form a monolayer. Based on our previous studies we concluded that the fetal cells are more potent than those isolated from the maternal placental tissues and that intramuscular (IM), versus intravenous delivery, was associated with no apparent adverse effects. The isolated f-hPSC were then further expanded for 6-8 passages before their use. Peripheral injection of 2 doses of 2x106 f-hPSC on day 1 and 4 following irradiation, both intramuscularly (IM) and subcutaneously (SC), dramatically increased the survival rate of the mice to >80% with a significant regain of their lost body weight and with a restoration of their depleted hematopoietic system. The recovery of f-hPSC treated mice was associated with the highly significant elevation in the level of circulating erythropoietin (EPO). Flow cytometry analyses of hematopoietic stem cells and of erythroid cells maturation in the spleen (SPL) and the bone marrow (BM) at the end of the experiment on day 23 following irradiation elucidate the fast recovery of the mice from ARS. A contribution of newly developed extra-medullary hematopoietic (EMH) islands in the SPL was recorded, though f-hPSC treatment was beneficial also for irradiated splenectomized mice. We expect that the beneficial f-hPSC treatment as a xenogeneic/allogeneic life-saving cell therapy should have clinical applications for the induction of hematopoiesis in ARS and possibly for other conditions associated with severe pancytopenia and BM failure. The f-hPSC have also proven to be a basis for highly potent therapies for other pro-regenerative applications which are now being tested.
E-mail: rafi@hadassah.org.il
