In vivo and in vitro effects of cord blood hematopoietic stem and progenitor cell (HSPC) expansion using valproic acid and/or nicotinamide

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dc.contributor.authorGencer, E.B.
dc.contributor.authorAkin, H.Y.
dc.contributor.authorToprak, S.K.
dc.contributor.authorTurasan, E.
dc.contributor.authorYousefzadeh, M.
dc.contributor.authorYurdakul-Mesutoglu, P.
dc.contributor.authorCagan M.
dc.date.accessioned2024-05-19T14:33:35Z
dc.date.available2024-05-19T14:33:35Z
dc.date.issued2024
dc.departmentİstinye Üniversitesien_US
dc.description.abstractBackground: High self-renewal capacity and most permissive nature of umbilical cord blood (CB) results with successful transplant outcomes but low hematopoietic stem and progenitor cell (HSPC) counts limits wider use. In order to overcome this problem ex vivo expansion with small molecules such as Valproic acid (VPA) or Nicotinamide (NAM) have been shown to be effective. To the best of our knowledge, the combinatory effects of VPA and NAM on HSPC expansion has not been studied earlier. The aim of this study was to analyze ex vivo and in vivo efficacy of VPA and NAM either alone or in combination in terms of expansion and engraftment. Methods: A total of 44 CB units were included in this study. To determine the ex vivo and in vivo efficacy, human CB CD34+ cells were expanded with VPA and/or NAM and colony forming unit (CFU) assay was performed on expanded HSPC. Xenotransplantation was performed simultaneously by intravenous injection of expanded HSPC to NOD-SCID gamma (NSG) mice (n = 22). Significance of the difference between the expansion groups or xenotransplantation models was analyzed using t-test, Mann-Whitney, ANOVA or Kruskal-Wallis tests as appropriate considering the normality of distributions and the number of groups analyzed. Results: In vitro CD34+ HSPC expansion fold relative to cytokines-only was significantly higher with VPA compared to NAM [2.23 (1.07–5.59) vs 1.48 (1.00–4.40); p < 0.05]. Synergistic effect of VPA+NAM has achieved a maximum relative expansion fold at 21 days (D21) of incubation [2.95 (1.00–11.94)]. There was no significant difference between VPA and VPA+NAM D21 (p = 0.44). Fold number of colony-forming unit granulocyte-macrophage (CFU-GM) colonies relative to the cytokine-only group was in favor of NAM compared to VPA [1.87 (1.00–3.59) vs 1.00 (1.00–1.81); p < 0.01]. VPA+NAM D21 [1.62 (1.00–2.77)] was also superior against VPA (p < 0.05). There was no significant difference between NAM and VPA+NAM D21. Following human CB34+ CB transplantation (CBT) in the mouse model, fastest in vivo leukocyte recovery was observed with VPA+NAM expanded cells (6 ± 2 days) and the highest levels of human CD45 chimerism was detectable with VPA-expanded CBT (VPA: 5.42 % at day 28; NAM: 2.45 % at day 31; VPA+NAM 1.8 % at day 31). Conclusion: Our study results suggest using VPA alone, rather than in combination with NAM or NAM alone, to achieve better and faster expansion and engraftment of CB HSPC. © 2024 Elsevier Masson SASen_US
dc.description.sponsorship2022K12-186770; Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, TÜBİTAK: 113S261; Türkiye Bilimler Akademisien_US
dc.description.sponsorshipThis study was supported by Turkish Ministry of Development Scientific Project (2022K12-186770), Turkish Academy of Sciences (TUBA) and The Scientific and Technological Research Council of Turkey (TUBITAK) 1001 Research Grant ( 113S261 ).en_US
dc.identifier.doi10.1016/j.retram.2024.103444
dc.identifier.issn2452-3186
dc.identifier.issue3en_US
dc.identifier.scopus2-s2.0-85186689839en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1016/j.retram.2024.103444
dc.identifier.urihttps://hdl.handle.net/20.500.12713/4279
dc.identifier.volume72en_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherElsevier Masson s.r.l.en_US
dc.relation.ispartofCurrent Research in Translational Medicineen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmz20240519_kaen_US
dc.subjectCd34 Expansionen_US
dc.subjectCord Blooden_US
dc.subjectHspc Transplantationen_US
dc.subjectNicotinamideen_US
dc.subjectValproic Aciden_US
dc.titleIn vivo and in vitro effects of cord blood hematopoietic stem and progenitor cell (HSPC) expansion using valproic acid and/or nicotinamideen_US
dc.typeArticleen_US

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