Hyperbaric Oxygen Therapy Improves Post-Transplant Umbilical Cord Blood Engraftment

Abstract

AbstractAbstract 4663 Background:Delayed engraftment following umbilical cord blood (UCB) transplantation is associated with increased transplant-related mortality. Earlier, we have reported that hyperbaric oxygen therapy (HBO) might have altered early UCB engraftment kinetics in a transplant animal model. Herein, we report use of HBO to improve long-term UCB engraftment. Methods:Six-to eight-week old NSG mice were sublethally irradiated 24 hours prior to CD34 selected UCB cell transplant. The irradiated mice were separated into a control group (where mice remained under normoxic conditions) and the HBO group (where mice received two hours of HBO therapy; 100% oxygen at 2.5 atmospheres absolute). Six hours after starting HBO therapy, both groups received 1×105 CD34 selected UCB cells via tail vein injection. The infused CD34 selected cells were transduced with a lentivirus carrying luciferase gene for in vivo imaging. Mice (n=4) from each treatment group were sacrificed after 3 and 4 months to assess long-term engraftment. Engraftment was measured as assessed by flow cytometry. Myeloid, B-cell, and T-cell subset engraftment was determined by flow cytometry. Results:At 3 and 4 months post-transplant, the mean percentage of human CD45 expressing cells in peripheral blood of HBO mice was significantly higher than controls (p=0.03 and p=.008 respectively). The mean percentage of human CD45 expression was higher in bone marrow of HBO mice at 3 months and 4 months, but only reached statistical significance at 4-month time point (p=0.04). At 3 months, the mean percentage of human CD19 expressing cells was significantly higher in peripheral blood of HBO mice (p=0.03) while no differences were noted between the two groups in terms of CD33 or CD3 expression. At 4 months, the mean percentage of human CD19 expressing cells and human CD3 expressing cells was significantly higher in peripheral blood of HBO mice (p=0.009 and p=0.0009, respectively) while no differences were noted between the two groups in terms of CD33 expression. Conclusions:HBO therapy given prior to UCB cell infusion significantly improved UCB's long-term engraftment. At 3 months, engraftment was skewed toward B-cell engraftment, while more balanced engraftment was noted at 4 months. Future studies are planned to confirm these findings and to determine the underlying mechanisms by which HBO improved UCB CD34 cell engraftment. Disclosures:No relevant conflicts of interest to declare.