Transplantation, gene therapy and intestinal pathology in MNGIE patients and mice

BMC Gastroenterology

Elly Bogaerts¹  Niek P. van Til²  Armin Finkenstedt³  Irenaeus F. de Coo⁴  Rana Yadak⁴  Dominique Cazals-Hatem⁵  Marianna Bugiani⁶  Max V. Boot⁶ 

[1] Department of Clinical Genetics, Erasmus University Medical Center;Department of Hematology, Erasmus University Medical Center;Department of Medicine I, Medical University of Innsbruck;Department of Neurology, Erasmus University Medical Center;Department of Pathology, Beaujon Hospital;Department of Pathology, VU University Medical Center;

关键词: Mitochondrial neurogastrointestinal encephalomyopathy;    Gastrointestinal symptoms;    HSCT;    HCSGT;    Hematopoietic stem cell gene therapy;    Cajal cells;   

DOI  :  10.1186/s12876-018-0881-0

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown