Spatial relationship between telocytes, interstitial cells of Cajal and the enteric nervous system in the human ileum and colon

Abstract

Telocytes (TCs) are recently described interstitial cells, present in almost all human organs. Among many other functions, TCs regulate gastrointestinal motility together with the interstitial cells of Cajal (ICCs). TCs and ICCs have close localization in the human myenteric plexus; however, the exact spatial relationship cannot be clearly examined by previously applied double immunofluorescence/confocal microscopy. Data on TCs and submucosal ganglia and their relationship to intestinal nerves are scarce. The aim of the study was to analyse the spatial relationship among these components in the normal human ileum and colon with double CD34/CD117 and CD34/S100 immunohistochemistry and high‐resolution light microscopy. TCs were found to almost completely encompass both myenteric and submucosal ganglia in ileum and colon. An incomplete monolayer of ICCs was localized between the TCs and the longitudinal muscle cells in ileum, whereas only scattered ICCs were present on both surfaces of the colonic myenteric ganglia. TC‐telopodes were observed within colonic myenteric ganglia. TCs, but no ICCs, were present within and around the interganglionic nerve fascicles, submucosal nerves and mesenterial nerves, but were only observed along small nerves intramuscularly. These anatomic differences probably reflect the various roles of TCs and ICCs in the bowel function.

Telocytes in the Normal and Pathological Peripheral Nervous System

“…The digestive tract (above the enteric wall) is an ideal anatomic region to understand TC characteristics, arrangement and functions [ 17 , 18 , 19 , 20 , 25 , 33 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ]. This adequacy for the study of TCs (specifically in the peripheral nervous system) is further increased in the neurogenic hyperplasias of the appendix and gallbladder, and the related processes.…”

3D analysis of the myenteric plexus of the human bowel by X-ray phase-contrast tomography – a future method?

“…Within and around the ganglion, the neurons, glial cells and spindle-shaped cells can be observed. In a previous study using double immunostaining, we could report that telocytes in the colon can both 'envelope' the ganglion, and can be situated within the ganglion, in close connection with neurons [4]. The phenomenon of probable penetration of fine projections from spindle-like cells into the ganglion could also be identified by the present method.…”

“…determine the connections between ENS, ICCs and fibroblast-like cells [4]. The volumes of fibroblast-like cells and ganglia were determined, but the whole volume of the ENS in the biopsies was not reported [10,20].…”

“…We can expect that further advancements in X-ray sources, phase retrieval and segmentation methods will improve differentiation of various cells in the future. At present, double/triple immunohistochemistry, with or without confocal fluorescence microscopy [4,7,8,[25][26][27], is a satisfactory, cheaper and quicker method for this purpose. However, staining and 3D visualization of myenteric ganglia by the new method of Graham and L opez et al [21] takes several weeks, and demands many manual steps.…”

“…The plexus consists of ganglia built up by neurons, their axons and dendrites, glial cells and connecting neuronal fascicles between the ganglia. In addition, interstitial cells of Cajal (ICCs) and telocytes (fibroblast-like cells in previous literature) with their long and thin cytoplasmic projections surround and penetrate the ganglia and nerves in certain localizations [4].…”