The microenvironment in the Hirschsprung's disease gut supports myenteric plexus growth

Abstract

The amount of the factors varied considerably between the individual segments and also from patient to patient. Four major expression patterns could be detected. While all extracts tested lead to a significant increase in neurite outgrowth compared to the control, extracts from proximal segments tended to have more prominent effects. In one experiment, extracts from all individual segments of a single patient were tested. Neurite outgrowth, neuronal survival, and branching pattern varied from segment to segment, but all HSCR-muscle-protein extracts increased neuronal survival and network formation. Smooth muscle protein from aganglionic bowel supports the survival and outgrowth of myenteric neurons and NCSCs and is so an appropriate target for neural stem cell treatment.

The influence of extracellular matrix composition on the differentiation of neuronal subtypes in tissue engineered innervated intestinal smooth muscle sheets

“…Neurotrophic factors (NT-3, Neurturin, GDNF) and morphogens (BMP-2/4) capable of driving enteric neuronal progenitor cell proliferation and differentiation have been demonstrated to arise from the smooth muscle and mesenchyme of the developing and adult gut [51-53]. Recently, the postnatal bowel was demonstrated to support the differentiation of enteric neuronal progenitor cells, strengthening the fact that cues for differentiation can be derived from the postnatal gut [54, 55]. Hence, it was expected that smooth muscle cells within the tissue engineered sheets would drive the differentiation of enteric neuronal progenitor cells.…”

Apoptotic neuron-secreted HN12 inhibits cell apoptosis in Hirschsprung's disease

“…31,32 Many studies have also shown that the microenvironment influences the pathogenesis of HSCR. 33,34 Our work is also the first time to identify the existence of exosomes in HSCR. Although more research is required to demonstrate the relationship between exosomes and the microenvironment in HSCR, it is supposed that exosomes possibly work through an abnormal extracellular matrix or through interactions with growth factors that are essential for intestinal neuronal network formation.…”

Advances in Neo-Innervation of the Gut

“…Both transfected genes were shown to be expressed by the neural cells, demonstrating the feasibility of this approach; however, the functional consequences of adding these genes was not assessed. Furthermore, factors originating from gut tissue of patients with Hischsprung's disease can stimulate enteric neural cell survival and differentiation, indicating that the gut microenvironment, although abnormal, may be permissive for engraftment and functioning of NPCs [51]. Altering genomic content or using ESCs can lead to tumor formation; therefore, a recent study was performed that successfully incorporated a "suicide gene" into ENPCs, which promotes cell death in ESCs that become malignant.…”

“…Transplanted progenitor cells have been shown to restore function 4 weeks after treatment through electrophysiological assessment, indicating that surviving neurons have the ability to restore gut function [36,38,40]. The gut environment in congenital diseases, such as Hirschsprung's disease, may lack important factors needed for neural cell survival [4]; however, recently it has been shown that SMCs isolated from these patients promoted neuron survival [51]. Growth factor supplementation to improve survival has been attempted; however, the addition of basic fibroblast growth factor to injected neural cells improved ganglion formation but had minimal impact of cell viability in rodent models [52].…”