Transplantation, gene therapy and intestinal pathology in MNGIE patients and mice.
BMC Gastroenterol
; 18(1): 149, 2018 Oct 19.
Article
en En
| MEDLINE
| ID: mdl-30340467
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Terapia Genética
/
Encefalomiopatías Mitocondriales
/
Trasplante de Células Madre Hematopoyéticas
/
Enfermedades Gastrointestinales
/
Intestino Delgado
Límite:
Adolescent
/
Adult
/
Animals
/
Child
/
Humans
Idioma:
En
Revista:
BMC Gastroenterol
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Países Bajos