Physiologic oxygen expansion of hematopoietic stem and progenitor cells (HSPCs) enhances lymphocyte recovery following transplantation 4028

Abstract Description Rapid recovery of lymphocytes post hematopoietic cell transplantation (HCT) is correlated with positive patient outcome in treatments of hematologic disease. Few effective clinical therapies exist to enhance lymphocyte recovery, indicating a clear unmet need. Ex vivo expansion of umbilical cord blood (CB) HSPCs is an FDA approved therapy to increase recovery of critical hematopoietic cells such as neutrophils and platelets, but impact on lymphocytes remains uncertain. Expansion under physiological oxygen (1-14% O2) results in increased lymphoid-biased RNA levels and lymphocyte progenitor cell numbers. After ex vivo expansion of murine HSPCs, nucleated cell counts increase and frequencies of HSPCs decrease as O2 tension increases. As a ratio of injected cells, mice transplanted with HSPCs expanded at 1% O2 had increased natural killer cell frequencies at weeks 1 and 10 and increased CD4 and dendritic cell frequencies at week 5 post HCT in the peripheral blood (PB) compared to transplantation with ambient air expanded (21% O2) HSPCs. Transplantation with huCD34+ CB HSPCs expanded at 1-14% O2 results in increased CD3+/CD19+ frequencies in the PB at week 10 post HCT compared to ambient air expansion. Transcriptomic analysis reveals differential mitochondrial gene expression in lymphocyte progenitors expanded under 1% O2 compared to 21% O2. Our results suggest expansion under physiological O2 is a viable strategy for improving lymphocyte recovery and patient outcome post HCT. Funding Sources NIH U54 DK106846; CTSI BRG; K99 HL166790 Topic Categories Transplantation Immunology (TRAN)