{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:34:54Z","timestamp":1787009694215,"version":"build-2736575974"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Michael Reese Pioneer in Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hematopoietic stem cell (HSC) transplantation is a potentially curative option for patients with hematologic malignancies, but donor shortages impact graft availability. Umbilical cord blood (UCB) is a viable alternative source of HSC; however, the limited numbers present in a single unit have spurred efforts to expand HSC ex vivo. We previously demonstrated that the addition of valproic acid (VPA), an anti-convulsive drug, to CB cell cultures promotes maintenance of functional HSC, but not expansion. However, it has been proposed that VPA primarily induces mitochondrial reprogramming of mature CD34+CD90\u2013 cells to more primitive CD34+CD90+ cells, rather than the replication of CD34+CD90+ cells in culture. To determine which fraction of the CD34+CD90+ cells present after culture in VPA were derived from CD34+CD90\u2013 vs. CD34+CD90+ cells, we examined the functionality of CD34+CD90+ cells derived from each flow cytometry-sorted population. During culture in VPA there was a significant increase in CD34+CD90+ cell number; the majority arising from pre-existing CD34+CD90+ cells, with minimal contribution from CD34+CD90\u2013 cells. Colony-forming unit (CFU) assays revealed reduced plating efficiency and xeno-transplantation studies demonstrated diminished in vivo hematopoietic reconstitution potential of CD34+CD90+ cells derived from relatively committed CD34+CD90\u2013 cells. Our findings indicate that while VPA supports CD34+CD90+ cell expansion, the CD34+CD90+ cells derived from CD34+CD90\u2013 cells are functionally more differentiated than those derived directly from CD34+CD90+ cells, with increased mitochondrial mass and membrane potential, but reduced regenerative potential. These results emphasize the need for functional assessments of culture-expanded HSCs to accurately determine their therapeutic potential.<\/jats:p>","DOI":"10.1093\/stmcls\/sxaf079","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T13:12:38Z","timestamp":1765285958000},"source":"Crossref","is-referenced-by-count":1,"title":["Valproic acid-expanded cord blood CD34+CD90+ cells are functionally distinct based on their origin"],"prefix":"10.1093","volume":"44","author":[{"given":"Al Rabee","family":"Kassis","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Illinois College of Medicine , Chicago, IL 60612,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amudha","family":"Ganapathy","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Illinois College of Medicine , Chicago, IL 60612,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Mechaal","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Illinois College of Medicine , Chicago, IL 60612,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungwon","family":"An","sequence":"additional","affiliation":[{"name":"Clinical Stem Cell Laboratory, UI Blood & Marrow Transplant Program, UI Health , Chicago, IL 60612,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G","family":"Quigley","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Illinois College of Medicine , Chicago, IL 60612,","place":["United States"]},{"name":"University of Illinois Cancer Center , Chicago, IL 60612,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"Mahmud","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Illinois College of Medicine , Chicago, IL 60612,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3113-9155","authenticated-orcid":false,"given":"Nadim","family":"Mahmud","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Illinois College of Medicine , Chicago, IL 60612,","place":["United States"]},{"name":"Clinical Stem Cell Laboratory, UI Blood & Marrow Transplant Program, UI Health , Chicago, IL 60612,","place":["United States"]},{"name":"University of Illinois Cancer Center , Chicago, IL 60612,","place":["United 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