{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T12:05:28Z","timestamp":1780142728775,"version":"3.54.0"},"reference-count":24,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca-Dipartimenti eccellenti"},{"name":"Italian Ministry of Health"},{"name":"University of Ferrara"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.<\/jats:p>","DOI":"10.3390\/ijms23158792","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T21:09:18Z","timestamp":1659992958000},"page":"8792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4503-2770","authenticated-orcid":false,"given":"Elisa","family":"Boschetti","sequence":"first","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy"},{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0666-4380","authenticated-orcid":false,"given":"Leonardo","family":"Caporali","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5862-8074","authenticated-orcid":false,"given":"Roberto","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Malagelada","sequence":"additional","affiliation":[{"name":"Centro de Investigacion Biomedica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), University Hospital Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Departament de Medicina, Universitat Autonoma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Accarino","sequence":"additional","affiliation":[{"name":"Centro de Investigacion Biomedica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), University Hospital Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Departament de Medicina, Universitat Autonoma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Dotti","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Neurological Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2884-6716","authenticated-orcid":false,"given":"Roberta","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5824-3118","authenticated-orcid":false,"given":"Giovanna","family":"Cenacchi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy"},{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1773-8330","authenticated-orcid":false,"given":"Loris","family":"Pironi","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0559-4875","authenticated-orcid":false,"given":"Vincenzo","family":"Stanghellini","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6258-5345","authenticated-orcid":false,"given":"Stefano","family":"Ratti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Manzoli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4923-6404","authenticated-orcid":false,"given":"Valerio","family":"Carelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy"},{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0867-5873","authenticated-orcid":false,"given":"Roberto","family":"De Giorgio","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.2169\/internalmedicine.45.6064","article-title":"Thymidine phosphorylase 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