Abstract

Placenta-derived stromal cells named PLX-R18 have been shown in-vitro to secrete pro-hematopoiesis proteins, induce bone marrow migration, and promote colony formation. Murine in-vivo studies indicated that placental cells are capable of reducing lethality from the Hematopoietic Sub-syndrome of Acute Radiation Syndrome (HS-ARS).

A NIAID-supported pilot study with non-human primate (NHP) rhesus macaque monkeys was conducted with the objective to characterize the effect of PLX-R18 on HS-ARS, including survival and hematological parameters in irradiated NHP. 62 male and female rhesus macaque monkeys were divided into irradiated and non-irradiated cohorts. Non-irradiated or irradiated NHPs were treated with three intramuscular doses of PLX-R18 at 1 and 5 days post irradiation, or with placebo control. All doses of PLX-R18 improved outcome of irradiated NHPs relative to placebo (dose of 4, 10 and 20M cells/kg increased survival by 33.3, 35.7 and 16.7% respectively).

A tendency towards earlier recovery of blood lineages was evident in all doses tested, particularly, for the two lower doses. The 4 million cells/kg dose of PLX-R18 reduced the duration of critical neutropenia, thrombocytopenia, and anemia (NEUT< 0.1x10^9/L, PLT< 10x10^9/L, HGB< 65 g/L) by 1.5, 1.5, and 0.7 days respectively. Importantly, NHP results recapitulate findings from mouse studies with respect to non-irradiated animals in that hematological parameters are minimally affected.

Taken together, all doses of PLX-R18 positively affected survival rates and multiple hematological parameters of HS-ARS in rhesus monkeys and had no negative effects in either irradiated or non-irradiated monkeys. This supports the intended development of PLX-R18 as a treatment for HS-ARS.

Disclosures

Sher: Pluristem LTD: Employment, Equity Ownership. Prezma: Pluristem LTD: Employment, Equity Ownership. Fuchs-Telem: Pluristem LTD: Employment, Equity Ownership. Shraga- Heled: Pluristem LTD: Employment, Equity Ownership. Authier: CiToxLAB: Employment. Chang: SRI International: Employment. Ascah: CiToxLAB: Employment. Bakke: SRI International: Employment. Gahagen: SRI International: Employment. Ofir: Pluristem LTD: Employment, Equity Ownership.

Author notes

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Asterisk with author names denotes non-ASH members.