Potential therapeutic effects of plx cells in microgravity conditions

Abstract

Background & Aim BACKGROUND - PLX are placenta-derived, mesenchymal-like adherent stromal cells that can be administered without the need for genetic matching. The PLX is currently in the late stage of Phase III multinational clinical trials for the treatment of critical limb ischemia and muscle injuries following surgery to repair hip fractures. The proposed mode of action is the release of soluble factors, such as cytokines and growth factors, to facilitate healing of damaged tissue by stimulating the body's natural repair processes. OBJECTIVE - To evaluate the potency of Placental eXpanded (PLX) cells, an allogenic, off-the-shelf, cell therapy product, in preventing adverse health outcomes during an extended period of simulated microgravity (hindlimb unloading, HU). Specifically, we assessed whether PLX treatment protects mice from adverse effects of simulated microgravity including immune system dysfunction, and deficits in muscle, bone, brain and marrow-derived osteoprogenitors. Methods, Results & Conclusion EXPERIMENT DESIGN -Animals: C57BL/6NJ mice; Four-month-old females at onset of treatment Treatment: Hindlimb unloading (HU) for 30 days and normally loaded controls (NL) in standard cages Intervention: PLX-PAD (maternal origin), PLX-R18 (fetal origin) or Sham (Plasmalyte) RESULTS - PLX treatment was well tolerated in a model for simulated weightlessness (HU) with no adverse effects on body weight and measures of neuroendocrine stress, such as circulating corticosterone levels and adrenal weight. In the hippocampus, a brain region important for cognition and memory, PLX prevented HU-induced decreases in protein levels of select cytokines. In contrast, PLX did not prevent HU-induced changes in circulating cytokine levels, bone loss, muscle atrophy nor immune cell differentials. CONCLUSIONS PLX treatment protected against some of the HU-induced changes in cytokine protein levels in the brain, confirming its immunomodulatory effects. Under the conditions of this study, PLX treatment did not prevent musculoskeletal deficits and immune cell population shifts caused by HU. PLX treatment was well tolerated in a model that simulates microgravity (HU) and therefore may be suitable for treating ischemic tissue damage due to injuries during long duration space travel; further studies are needed.