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Physiologic oxygen expanded hematopoietic stem and progenitor cells (HSPCs) represent an *ex vivo* cell therapy designed to enhance lymphocyte recovery following hematopoietic cell transplantation (HCT) for hematologic diseases. This approach involves culturing HSPCs under physiologic oxygen conditions (physioxia; 1-14% O2), in contrast to standard ambient air laboratory processing (21% O2). Preclinical studies indicate that transplantation with these physioxia-expanded cells leads to increased frequencies of natural killer (NK) cells, CD4 T cells, and dendritic cells in the peripheral blood and bone marrow. Furthermore, donor-derived CD4 and CD8 T cells from the physioxia cohort exhibit increased expression of CD44, a marker of homeostatic proliferation, suggesting more efficient lymphocyte recovery. Importantly, the functionality of mature donor-derived T-lymphocytes is preserved, with no changes in activation or terminal differentiation markers, and maintained cytokine production upon stimulation. This therapy aims to address the delayed T cell recovery and reduced cytokine production often observed in umbilical cord blood recipients.
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