{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:12:00Z","timestamp":1793761920435,"version":"4.6.1"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001677","name":"INSERM","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004099","name":"Ligue Nationale contre le Cancer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004099","name":"Ligue R\u00e9gionale Contre le Cancer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Network RISK-IR"},{"name":"EUR G.E.N.E","award":["#ANR-17-EURE-0013"],"award-info":[{"award-number":["#ANR-17-EURE-0013"]}]},{"DOI":"10.13039\/501100021716","name":"Universit\u00e9 de Paris","doi-asserted-by":"publisher","award":["#ANR\u201418-IDEX-0001"],"award-info":[{"award-number":["#ANR\u201418-IDEX-0001"]}],"id":[{"id":"10.13039\/501100021716","id-type":"DOI","asserted-by":"publisher"}]},{"name":"French Government"},{"name":"Investments for the Future"},{"name":"Ligue Nationale Contre le Cancer and a Doctoral Mentor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In a steady state, hematopoietic stem cells (HSC) exhibit very low levels of reactive oxygen species (ROS). Upon stress, HSC get activated and enter into proliferation and differentiation process to ensure blood cell regeneration. Once activated, their levels of ROS increase, as messengers to mediate their proliferation and differentiation programs. However, at the end of the stress episode, ROS levels need to return to normal to avoid HSC exhaustion. It was shown that antioxidants can prevent loss of HSC self-renewal potential in several contexts such as aging or after exposure to low doses of irradiation suggesting that antioxidants can be used to maintain HSC functional properties upon culture-induced stress. Indeed, in humans, HSC are increasingly used for cell and gene therapy approaches, requiring them to be cultured for several days. As expected, we show that a short culture period leads to drastic defects in HSC functional properties. Moreover, a switch of HSC transcriptional program from stemness to differentiation was evidenced in cultured HSC. Interestingly, cultured-HSC treated with 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (4-hydroxy-TEMPO or Tempol) exhibited a higher clonogenic potential in secondary colony forming unit cell (CFU-C) assay and higher reconstitution potential in xenograft model, compared to untreated cultured-HSC. By transcriptomic analyses combined with serial CFU-C assays, we show that Tempol, which mimics superoxide dismutase, protects HSC from culture-induced stress partly through VEGF\u03b1 signaling. Thus, we demonstrate that adding Tempol leads to the protection of HSC functional properties during ex vivo culture.<\/jats:p>","DOI":"10.1093\/stcltm\/szad049","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T17:37:11Z","timestamp":1692898631000},"page":"676-688","source":"Crossref","is-referenced-by-count":8,"title":["The Antioxidant TEMPOL Protects Human Hematopoietic Stem Cells From Culture-Mediated Loss of Functions"],"prefix":"10.1093","volume":"12","author":[{"given":"Elia","family":"Henry","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, CEA, Stabilit\u00e9 G\u00e9n\u00e9tique Cellules Souches et Radiations , F-92260 Fontenay-aux-Roses , France"},{"name":"Universit\u00e9 Paris-Saclay, INSERM, CEA, Stabilit\u00e9 G\u00e9n\u00e9tique Cellules Souches et Radiations , F-92260 Fontenay-aux-Roses , France"},{"name":"Laboratoire des cellules Souches H\u00e9matopo\u00ef\u00e9tiques et des Leuc\u00e9mies, Equipe Niche et Cancer dans l\u2019H\u00e9matopo\u00ef\u00e8se, \u00e9quipe labellis\u00e9e Ligue Nationale Contre le Cancer, UMR1274-E008, INSERM, CEA , F-92265 Fontenay-aux Roses , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Picou","sequence":"additional","affiliation":[{"name":"CNRS EMR 7001 LNOx Leukemic Niche and Redox Metabolism , Tours , France"},{"name":"EA 7501, Universit\u00e9 de Tours , Tours , France"},{"name":"Department of Biological Hematology, Tours University Hospital , Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilma","family":"Barroca","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, CEA, Stabilit\u00e9 G\u00e9n\u00e9tique Cellules Souches et Radiations , F-92260 Fontenay-aux-Roses , France"},{"name":"Universit\u00e9 Paris-Saclay, INSERM, CEA, Stabilit\u00e9 G\u00e9n\u00e9tique Cellules Souches et Radiations , F-92260 Fontenay-aux-Roses , 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Six","sequence":"additional","affiliation":[{"name":"Human Lymphohematopoiesis Laboratory, Universit\u00e9 Paris Cit\u00e9, Imagine Institute, INSERM UMR 1163 , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Gobeaux","sequence":"additional","affiliation":[{"name":"Biochemistry Department\/Diagnostic Biologique Automatis\u00e9 (SDBA), DMU sBioPhyGen, Cochin Hospital-Universit\u00e9 de Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Auberger","sequence":"additional","affiliation":[{"name":"OPALE Carnot Institute, The Organization for Partnerships in Leukemia, Saint-Louis Hospital , 75010 Paris , France"},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, C3M\/INSERM U1065 , Nice , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"H\u00e9rault","sequence":"additional","affiliation":[{"name":"CNRS EMR 7001 LNOx Leukemic Niche and Redox Metabolism , Tours , France"},{"name":"Department of Biological Hematology, Tours University Hospital , Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Pflumio","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, CEA, Stabilit\u00e9 G\u00e9n\u00e9tique Cellules Souches et Radiations , F-92260 Fontenay-aux-Roses , France"},{"name":"Laboratoire des cellules Souches H\u00e9matopo\u00ef\u00e9tiques et des Leuc\u00e9mies, Equipe Niche et Cancer dans l\u2019H\u00e9matopo\u00ef\u00e8se, \u00e9quipe labellis\u00e9e Ligue Nationale Contre le Cancer, UMR1274-E008, INSERM, CEA , F-92265 Fontenay-aux Roses , France"},{"name":"OPALE Carnot Institute, The Organization for Partnerships in Leukemia, Saint-Louis Hospital , 75010 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1726-1472","authenticated-orcid":false,"given":"Marie-Laure","family":"Arcangeli","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, CEA, Stabilit\u00e9 G\u00e9n\u00e9tique Cellules Souches et Radiations , F-92260 Fontenay-aux-Roses , France"},{"name":"Universit\u00e9 Paris-Saclay, INSERM, CEA, Stabilit\u00e9 G\u00e9n\u00e9tique Cellules Souches et Radiations , F-92260 Fontenay-aux-Roses , France"},{"name":"Laboratoire des cellules Souches H\u00e9matopo\u00ef\u00e9tiques et des Leuc\u00e9mies, Equipe Niche et Cancer dans l\u2019H\u00e9matopo\u00ef\u00e8se, \u00e9quipe labellis\u00e9e Ligue Nationale Contre le Cancer, UMR1274-E008, INSERM, CEA , F-92265 Fontenay-aux Roses , France"},{"name":"OPALE Carnot Institute, The Organization for Partnerships in Leukemia, Saint-Louis Hospital , 75010 Paris , France"},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, C3M\/INSERM U1065 , Nice , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,24]]},"reference":[{"key":"2023100513360261500_CIT0001","first-page":"120","article-title":"Hematopoiesis: a human perspective","volume-title":"Cell Stem Cell","author":"Doulatov","year":"2012"},{"key":"2023100513360261500_CIT0002","first-page":"635","article-title":"Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood","volume-title":"Cell Stem Cell","author":"Majeti","year":"2007"},{"key":"2023100513360261500_CIT0003","first-page":"303","article-title":"Haematopoietic stem cell activity and interactions with the niche","volume-title":"Nat Rev Mol Cell Biol","author":"Pinho","year":"2019"},{"key":"2023100513360261500_CIT0004","first-page":"447","article-title":"Gene therapy targeting haematopoietic stem cells for inherited diseases: progress and challenges","volume-title":"Nat Rev Drug 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Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal","volume-title":"Science","author":"Fares","year":"2014"},{"key":"2023100513360261500_CIT0026","first-page":"e134","article-title":"Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1-2 safety and feasibility study","volume-title":"Lancet Haematol","author":"Cohen","year":"2020"},{"key":"2023100513360261500_CIT0027","first-page":"410.e1","article-title":"UM171 expansion of cord blood improves donor availability and HLA matching for all patients, including minorities","volume-title":"Transplant Cell Ther","author":"Dumont-Lagac\u00e9","year":"2022"},{"key":"2023100513360261500_CIT0028","first-page":"2044","article-title":"Human hematopoietic stem\/progenitor cells display reactive oxygen species-dependent long-term hematopoietic defects after exposure to low doses of ionizing 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