{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:36:41Z","timestamp":1790638601938,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Huntington\u2019s disease (HD) is a neurodegenerative disorder caused by cytosine-adenine-guanine (CAG) triplet expansion in the HTT gene, producing a mutant Huntingtin protein that impairs mitochondrial dynamics by reducing fusion and increasing fission. Mesenchymal stem cells (MSCs) have shown potential therapeutic effects by sharing functional mitochondria and other secretomes. In this study, quinolinic acid-lesioned neuro-2a (QA-N2a) cells and glutamatergic neurons with 50 CAG repeats (HD neurons) were co-cultured with human umbilical cord-derived MSCs for 5\u2009hours. For QA-N2a cells, immunocytochemistry (ICC) was performed to demonstrate the change in GABA and Substance P before and after co-culture. For HD neurons, ICC was conducted to identify mitochondrial proteins, while Western blot was employed to evaluate proteins related to inflammation and mitochondrial function. As a result, co-culture with MSC significantly restored the expression of GABA and Substance P, which diminished after QA exposure. In HD neurons co-cultured with MSCs, an increase in mitochondrial abundance was observed, with significantly higher intensity and dendritic distribution of mitochondria compared to control cells. Western blot analysis confirmed this increase and showed a rising trend in ATP5a levels. MSCs also promoted mitochondrial fusion, indicated by higher levels of Mitofusin 2 (MFN2) and Mitochondrial Dynamin Like GTPase (OPA1), and a trend of reduction in the fission marker Dynamin-Related Protein (DRP1). Additionally, the co-culture led to a decreased trend in neuroinflammation markers IL-6, TNF-\u03b1, MMP9, and p-NFkB. Collectively, this study demonstrates that MSCs alleviate HD pathology by restoring the mitochondria activity and potentially suppressing inflammation in two different HD in vitro models.<\/jats:p>","DOI":"10.1093\/stmcls\/sxag019","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T11:35:28Z","timestamp":1775561728000},"source":"Crossref","is-referenced-by-count":1,"title":["Stem cells enhance mitochondrial function in experimental Huntington\u2019s disease"],"prefix":"10.1093","volume":"44","author":[{"given":"Francesco","family":"D\u2019Egidio","sequence":"first","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila 67100, L\u2019Aquila,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Napasiri","family":"Putthanbut","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University , Siriraj, Bangkok Noi, Bangkok 10700,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Starahs","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine , Tampa, FL 33612,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jea Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Stem Cell Biomedical Applications Inc , Wildwood, FL 34785,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2966-9782","authenticated-orcid":false,"given":"Cesario V","family":"Borlongan","sequence":"additional","affiliation":[{"name":"Stem Cell Biomedical Applications Inc , Wildwood, FL 34785,","place":["United 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