Improved Hematopoiesis in GS-Nitroxide (JP4-039)-treated Mouse Long-term Bone Marrow Cultures and Radioresistance of Derived Bone Marrow Stromal Cell Lines

Aim: To determine if the small-molecule radioprotector GS-nitroxide, JP4-039, improved hematopoiesis in long-term bone marrow cultures (LTBMCs), explanted marrow from in vivo drug-treated C57BL/6NTac mice was maintained in JP4-039 for 25 weeks. Hematopoietic cell production and radiobiology of derived stromal cell lines was measured. Materials and Methods: Groups of LTBMCs were established from mouse groups. Stromal cell lines were established from the adherent layer of JP4-039-treated and untreated control groups. Results: LTBMCs maintained in JP4-039 exhibited increased production of total non-adherent and 7-day and 14-day hematopoietic colony-forming cells. Stromal cell lines derived from JP4-039-treated cultures were radioresistant in vitro, demonstrated a distinct squamousl epithelial morphology and overexpressed Nrf2, Ctgf, Lox, Tlr1 collagen la, Brd3, and Brd4. Conclusion: Chronic treatment of bone marrow cultures and derived stromal cell lines with JP4-039 was non-toxic, and conferred resistance to oxidative stress.