دورية أكاديمية
Transplantation, gene therapy and intestinal pathology in MNGIE patients and mice.
| العنوان: | Transplantation, gene therapy and intestinal pathology in MNGIE patients and mice. |
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| المؤلفون: | Yadak R; Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.; Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands., Boot MV; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., van Til NP; Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Cazals-Hatem D; Department of Pathology, Beaujon Hospital, Clichy, France., Finkenstedt A; Department of Medicine I, Medical University of Innsbruck, Innsbruck, Austria., Bogaerts E; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., de Coo IF; Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands., Bugiani M; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. m.bugiani@vumc.nl. |
| المصدر: | BMC gastroenterology [BMC Gastroenterol] 2018 Oct 19; Vol. 18 (1), pp. 149. Date of Electronic Publication: 2018 Oct 19. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 100968547 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-230X (Electronic) Linking ISSN: 1471230X NLM ISO Abbreviation: BMC Gastroenterol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : BioMed Central, [2001- |
| مواضيع طبية MeSH: | Genetic Therapy* , Hematopoietic Stem Cell Transplantation*, Gastrointestinal Diseases/*pathology , Gastrointestinal Diseases/*therapy , Intestine, Small/*pathology , Mitochondrial Encephalomyopathies/*pathology , Mitochondrial Encephalomyopathies/*therapy, Adolescent ; Animals ; Child ; Disease Models, Animal ; Humans ; Interstitial Cells of Cajal/pathology ; Mice ; Muscular Atrophy/pathology ; Young Adult |
| مستخلص: | Background: Gastrointestinal complications are the main cause of death in patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Available treatments often restore biochemical homeostasis, but fail to cure gastrointestinal symptoms. Methods: We evaluated the small intestine neuromuscular pathology of an untreated MNGIE patient and two recipients of hematopoietic stem cells, focusing on enteric neurons and glia. Additionally, we evaluated the intestinal neuromuscular pathology in a mouse model of MNGIE treated with hematopoietic stem cell gene therapy. Quantification of muscle wall thickness and ganglion cell density was performed blind to the genotype with ImageJ. Significance of differences between groups was determined by two-tailed Mann-Whitney U test (P < 0.05). Results: Our data confirm that MNGIE presents with muscle atrophy and loss of Cajal cells and CD117/c-kit immunoreactivity in the small intestine. We also show that hematopoietic stem cell transplantation does not benefit human intestinal pathology at least on short-term. Conclusions: We suggest that hematopoietic stem cell transplantation may be insufficient to restore intestinal neuropathology, especially at later stages of MNGIE. As interstitial Cajal cells and their networks play a key role in development of gastrointestinal dysmotility, alternative therapeutic approaches taking absence of these cells into account could be required. |
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| معلومات مُعتمدة: | SSW0645 Sophia Foundation |
| فهرسة مساهمة: | Keywords: CD117/c-kit; Cajal cells; Gastrointestinal symptoms; HCSGT; HSCT; Hematopoietic stem cell gene therapy; Mitochondrial neurogastrointestinal encephalomyopathy |
| تواريخ الأحداث: | Date Created: 20181021 Date Completed: 20181108 Latest Revision: 20181114 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC6194683 |
| DOI: | 10.1186/s12876-018-0881-0 |
| PMID: | 30340467 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1471-230X |
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| DOI: | 10.1186/s12876-018-0881-0 |