Telocytes' Role in Modulating Gut Motility Function and Development: Medical Hypotheses and Literature Review

Abstract

This review article explores the telocytes' roles in inflammatory bowel diseases (IBD), presenting the mechanisms and hypotheses related to epithelial regeneration, progressive fibrosis, and dysmotility as a consequence of TCs' reduced or absent number. Based on the presented mechanisms and hypotheses, we aim to provide a functional model to illustrate TCs' possible roles in the normal and pathological functioning of the digestive tract. TCs are influenced by the compression of nearby blood vessels and the degree of fibrosis of the surrounding tissues and mediate these processes in response. The changes in intestinal tube vascularization induced by the movement of the food bowl, and the consequent pH changes that show an anisotropy in the thickness of the intestinal tube wall, have led to the identification of a pattern of intestinal tube development based on telocytes' ability to communicate and modulate surrounding cell functions. In the construction of the theoretical model, given the predictable occurrence of colic in the infant, the two-layer arrangement of the nerve plexuses associated with the intestinal tube was considered to be incompletely adapted to the motility required with a diversified diet. There is resulting evidence of possible therapeutic targets for diseases associated with changes in local nerve tissue development.

Keywords: Crohn’s disease; infant colic; inflammatory bowel diseases; irritable bowel syndrome; telocytes; ulcerative colitis.

Figure 1

SC-stem cells, FBS-fibroblasts, NS-neurons, SMC-smooth muscle cell; Breaking the balance between the two ways of stimulating TCs (positive and negative) can lead to either an increase or local decrease in digestive motility, mediated by morphological and functional changes. These changes are currently highlighted at the level of fibrosis and/or neuronal plexus development, although the signaling pathways are much more complex.

Figure 2

Submucous and myenteric nerve plexuses’ organization showing how modulating the pH as a response to mechanical stimuli from the intestinal lumen influences the neurons through the telocytes’ response to these stimuli.

Figure 3

Mechanical compression induces anisotropy of pH changes; first submucosal vessels are affected and subsequently the pH-dependent vascular compensatory mechanisms.

Figure 4

Modulation of the consistency of intestinal content by different intestinal bacterial populations.

Figure 5

Theoretical model on the reversible progression of maturation changes of the submucosal and myenteric nerve plexus under the influence of TCs modulated by membrane fluidity changes secondary to bacterial populations with a membrane lipid composition not adapted to local conditions.

Figure 6

The proposed therapeutic strategy for the reduction in intestinal colic.

Figure 7

Proposed strategy for treating Crohn’s disease by targeting dependent and pH-independent vascular hyperreactivity, and by direct targeting of TCs migration.