{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:03:24Z","timestamp":1788404604335,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"l\u2019Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-24-CE19-3040-02"],"award-info":[{"award-number":["ANR-24-CE19-3040-02"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"award":["ANR-24-CE19-3040-02"],"award-info":[{"award-number":["ANR-24-CE19-3040-02"]}],"id":[{"id":"https:\/\/ror.org\/00rbzpz17","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007380","name":"Fondation de l\u2019Avenir","doi-asserted-by":"publisher","award":["AP-RM-23-017"],"award-info":[{"award-number":["AP-RM-23-017"]}],"id":[{"id":"10.13039\/100007380","id-type":"DOI","asserted-by":"publisher"}]},{"award":["AP-RM-23-017"],"award-info":[{"award-number":["AP-RM-23-017"]}],"id":[{"id":"https:\/\/ror.org\/02dddmh90","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Contrat doctoral MESR Universit\u00e9 de Paris-Cit\u00e9"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Advanced glycation end products (AGEs) and oxidative stress (OS) have been linked to bone complications related to type 2 diabetes mellitus (T2DM). However, the effects of AGEs and OS on bone marrow mesenchymal stromal cells (BMMSCs), which play a key role in bone homeostasis and repair, remain unclear. Objectives: This study aimed to investigate the effects of AGEs on BMMSCs function and the ability of N-acetylcysteine (NAC) to alleviate AGE-induced OS in a T2DM context. Methods: Bone marrow (BM) and BMMSCs were isolated from Zucker diabetic fatty (ZDF) rats, which serve as a T2DM model, and their lean littermates (ZL, controls) at 24 weeks of age. Results: The results show that long-standing T2DM leads to changes in the BM\u2019s cellular composition and BMMSCs function that are distinct from age-related changes. In vitro, AGEs decreased BMMSCs viability, proliferation, and migration. The effects of AGEs were stronger in BMMSCs derived from a T2DM microenvironment. In both T2DM- and ZL-BMMSCs, AGEs induced cytoplasmic ROS, which was differentially reduced by NAC. The effect of NAC on T2DM-BMMSCs was greater when the cells were pre-treated with NAC 24 h before exposure to AGEs, whereas simultaneous exposure to both resulted in a smaller effect. Conclusions: These results show that AGEs impair BMMSCs expansion and functionality. AGE-induced ROS generation may be a critical factor in this impairment, while NAC was able to reduce OS in BMMSCs from a T2DM context. These findings highlight the vicious negative effects of the T2DM microenvironment on BMMSCs and underscore the need for further studies to better understand the underlying mechanisms and to explore strategies aimed at mitigating OS in the T2DM context.<\/jats:p>","DOI":"10.3390\/pharmaceutics18050595","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:39:34Z","timestamp":1779295174000},"page":"595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Type 2 Diabetes Modulates Mesenchymal Stem Cell Response to Advanced Glycation End Products and N-Acetylcysteine Antioxidant Effect"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6827-9437","authenticated-orcid":false,"given":"Rebecca","family":"Landon","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS UMR7052, INSERM U1271, ENVA, B3OA, F-75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Ding","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS UMR7052, INSERM U1271, ENVA, B3OA, F-75010 Paris, France"},{"name":"Laboratory for Vascular Translational Science (LVTS), Cardiovascular Bioengineering, Universit\u00e9 Sorbonne Paris Nord, Inserm U1148, F-93430 Villetaneuse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4986-7126","authenticated-orcid":false,"given":"William Ndjidda","family":"Bakari","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS UMR7052, INSERM U1271, ENVA, B3OA, F-75010 Paris, France"},{"name":"Laboratory for Vascular Translational Science (LVTS), Cardiovascular Bioengineering, Universit\u00e9 Sorbonne Paris Nord, Inserm U1148, F-93430 Villetaneuse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7936-678X","authenticated-orcid":false,"given":"Nathanael","family":"Larochette","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS UMR7052, INSERM U1271, ENVA, B3OA, F-75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanane","family":"El-Hafci","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS UMR7052, INSERM U1271, ENVA, B3OA, F-75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Thibaudeau","sequence":"additional","affiliation":[{"name":"H\u00f4pital Bichat-Claude-Bernard, Plateau de Morphologie UMR 1152, Universit\u00e9 Paris Cit\u00e9, F-75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abolfazl","family":"Barzegari","sequence":"additional","affiliation":[{"name":"Laboratory for Vascular Translational Science (LVTS), Cardiovascular Bioengineering, Universit\u00e9 Sorbonne Paris Nord, Inserm U1148, F-93430 Villetaneuse, France"},{"name":"Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz 51656-65931, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2500-0747","authenticated-orcid":false,"given":"Virginie","family":"Gueguen","sequence":"additional","affiliation":[{"name":"Laboratory for Vascular Translational Science (LVTS), Cardiovascular Bioengineering, Universit\u00e9 Sorbonne Paris Nord, Inserm U1148, F-93430 Villetaneuse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5819-1071","authenticated-orcid":false,"given":"Graciela","family":"Pavon-Djavid","sequence":"additional","affiliation":[{"name":"Laboratory for Vascular Translational Science (LVTS), Cardiovascular Bioengineering, Universit\u00e9 Sorbonne Paris Nord, Inserm U1148, F-93430 Villetaneuse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fani","family":"Anagnostou","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS UMR7052, INSERM U1271, ENVA, B3OA, F-75010 Paris, France"},{"name":"Department of Odontology, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Piti\u00e9-Salp\u00eatri\u00e8re Hospital, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Federation (2025). 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