ArticleStem cell research & therapy2025
Isoproterenol infusion enhances composition and function of G-CSF mobilized allogeneic peripheral blood hematopoietic cell grafts.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06643221 (Exercise-induced Adrenergic Receptor Signaling as an Immune Adjuvant for Allogeneic Cell Therapies), which is not on this map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Exercise-induced Adrenergic Receptor Signaling as an Immune Adjuvant for Allogeneic Cell Therapies
Who cites it
2 citing papers in PubMed.
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Authors and funding
13 authors.
Funding
Abstract
backgroundGraft-versus-host disease (GvHD) and relapse remain critical challenges in allogeneic hematopoietic cell transplantation (alloHCT). Graft composition is pivotal, with naïve T cells increasing GvHD risk and NK cells improving graft-versus-leukemia (GvL) effects. Acute beta-adrenergic receptor activation mobilizes effector lymphocytes, favorably altering circulating immune cell composition. This study investigated whether infusing the non-selective beta-agonist isoproterenol (ISO) after granulocyte colony-stimulating factor (G-CSF) mobilization enhances peripheral blood hematopoietic cell (PBHC) graft composition and outcomes.
methodsTen healthy volunteers received a 20-minute ISO infusion before and after five days of G-CSF hematopoietic cell mobilization. G-CSF and G-CSF + ISO mobilized PBHCs were phenotyped and assessed for in vitro cytotoxicity. NSG leukemia-bearing mice were injected with G-CSF or G-CSF + ISO mobilized PBHCs and monitored for GvHD, tumor burden, and overall survival.
resultsAfter G-CSF mobilization, ISO increased the numbers of CD34 + cells in the blood and favorably altered graft composition, increasing NK (9.5% to 27.9%) and TCR-γδ T cells (5.0% to 7.5%) while reducing naïve CD4 (18.1% to 11.2%) and CD8 (8.9% to 5.8%) T cells. Effector lymphocytes mobilized by G-CSF + ISO, particularly effector-memory CD8 + T-cells and NK-cells, exhibited upregulated genes and enriched gene sets linked to anti-tumor activity (e.g. NKG7, GZMB, NK cells cytotoxicity). This resulted in an 8-fold increase in cytolysis against the K562 leukemia cell line compared to PBHC mobilized by G-CSF only. In xenogeneic mice, G-CSF + ISO grafts reduced GvHD, extended survival, and improved GvL effects, with 42% of mice surviving at day 40 compared to 21% for G-CSF grafts.
conclusionsISO infusion post-G-CSF mobilization favorably enhances graft composition, mitigates GvHD, prolongs survival, and augments GvL effects. Our findings suggest that acute systemic beta-adrenergic receptor activation could be a valuable strategy to enhance outcomes in alloHCT.
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