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Graft composition is pivotal, with na\u00efve 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ten healthy volunteers received a 20-minute ISO infusion before and after five days of G-CSF hematopoietic cell mobilization. G-CSF and G-CSF\u2009+\u2009ISO mobilized PBHCs were phenotyped and assessed for in vitro cytotoxicity. NSG leukemia-bearing mice were injected with G-CSF or G-CSF\u2009+\u2009ISO mobilized PBHCs and monitored for GvHD, tumor burden, and overall survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After G-CSF mobilization, ISO increased the numbers of CD34\u2009+\u2009cells in the blood and favorably altered graft composition, increasing NK (9.5% to 27.9%) and TCR-\u03b3\u03b4 T cells (5.0% to 7.5%) while reducing na\u00efve CD4 (18.1% to 11.2%) and CD8 (8.9% to 5.8%) T cells. Effector lymphocytes mobilized by G-CSF\u2009+\u2009ISO, particularly effector-memory CD8\u2009+\u2009T-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\u2009+\u2009ISO grafts reduced GvHD, extended survival, and improved GvL effects, with 42% of mice surviving at day 40 compared to 21% for G-CSF grafts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ISO 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s13287-025-04725-4","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T11:47:44Z","timestamp":1762343264000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Isoproterenol infusion enhances composition and function of G-CSF mobilized allogeneic peripheral blood hematopoietic cell grafts"],"prefix":"10.1186","volume":"16","author":[{"given":"Helena","family":"Batatinha","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace M.","family":"Niemiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole A.","family":"Pe\u00f1a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovannah A.","family":"Hoskin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany M.","family":"Z\u00fa\u00f1iga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle A.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Forrest L.","family":"Baker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglass M.","family":"Diak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preteesh L.","family":"Mylabathula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy M.","family":"Kistner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Seckeler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Katsanis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"issue":"1","key":"4725_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1097\/MAJ.0b013e31824c6f29","volume":"345","author":"WC Yang","year":"2013","unstructured":"Yang WC, Chen YT, Chang WW, Chang CH, Fan PC, Lee SY, et al. 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Written informed consent and medical history were obtained from each participant after a proper explanation of the procedures and risks. The experiments with mice were approved by the University of Arizona Institutional Animal Care and Use Committee (IACUC) under protocol number 17\u2013338 \u201cHuman PBMC xenotransplantation into mice with cancer\u201d on 06\/01\/2018.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"There are no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"614"}}