{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T03:30:05Z","timestamp":1779334205045,"version":"3.51.4"},"reference-count":24,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Dutch \u201cPrinses Beatrix Spierfonds\u201d","award":["PBS W.0R15-09"],"award-info":[{"award-number":["PBS W.0R15-09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In 25% of patients with mitochondrial myopathies, pathogenic mitochondrial DNA (mtDNA) mutation are the cause. For heteroplasmic mtDNA mutations, symptoms manifest when the mutation load exceeds a tissue-specific threshold. Therefore, lowering the mutation load is expected to ameliorate disease manifestations. This can be achieved by fusing wild-type mesoangioblasts with mtDNA mutant myotubes. We have tested this in vitro for female carriers of the m.3271T&gt;C or m.3291T&gt;C mutation (mutation load &gt;90%) using wild-type male mesoangioblasts. Individual fused myotubes were collected by a newly-developed laser capture microdissection (LCM) protocol, visualized by immunostaining using an anti-myosin antibody. Fusion rates were determined based on male-female nuclei ratios by fluorescently labelling the Y-chromosome. Using combined \u2018wet\u2019 and \u2018air dried\u2019 LCM imaging improved fluorescence imaging quality and cell yield. Wild-type mesoangioblasts fused in different ratios with myotubes containing either the m.3271T&gt;C or the m.3291T&gt;C mutation. This resulted in the reduction of the mtDNA mutation load proportional to the number of fused wild-type mesoangioblasts for both mtDNA mutations. The proportional reduction in mtDNA mutation load in vitro after fusion is promising in the context of muscle stem cell therapy for mtDNA mutation carriers in vivo, in which we propose the same strategy using autologous wild-type mesoangioblasts.<\/jats:p>","DOI":"10.3390\/ijms24032679","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:29:03Z","timestamp":1675218543000},"page":"2679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Fusion of Wild-Type Mesoangioblasts with Myotubes of mtDNA Mutation Carriers Leads to a Proportional Reduction in mtDNA Mutation Load"],"prefix":"10.3390","volume":"24","author":[{"given":"Ruby","family":"Zelissen","sequence":"first","affiliation":[{"name":"Department of Toxicogenomics, Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"},{"name":"School for Developmental Biology and Oncology (GROW), Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Somaieh","family":"Ahmadian","sequence":"additional","affiliation":[{"name":"Department of Toxicogenomics, Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"},{"name":"School for Developmental Biology and Oncology (GROW), Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"},{"name":"Department of Molecular Cell Biology, Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaquin","family":"Montilla-Rojo","sequence":"additional","affiliation":[{"name":"Anatomy and Physiology, Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CS Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Timmer","sequence":"additional","affiliation":[{"name":"Department of Toxicogenomics, Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"},{"name":"School for Developmental Biology and Oncology (GROW), Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"Ummelen","sequence":"additional","affiliation":[{"name":"School for Developmental Biology and Oncology (GROW), Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"},{"name":"Department of Molecular Cell Biology, Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Hopman","sequence":"additional","affiliation":[{"name":"School for Developmental Biology and Oncology (GROW), Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"},{"name":"Department of Molecular Cell Biology, Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubert","family":"Smeets","sequence":"additional","affiliation":[{"name":"Department of Toxicogenomics, Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"},{"name":"School for Developmental Biology and Oncology (GROW), Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"},{"name":"School for Mental Health and Neurosciences (MHeNS), Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3278-2521","authenticated-orcid":false,"given":"Florence","family":"van Tienen","sequence":"additional","affiliation":[{"name":"Department of Toxicogenomics, Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"},{"name":"School for Mental Health and Neurosciences (MHeNS), Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/ana.24362","article-title":"Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease","volume":"77","author":"Gorman","year":"2015","journal-title":"Ann. 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