Telocytes express PDGFRα in the human gastrointestinal tract

Abstract

Telocytes (TC), a cell population located in the connective tissue of many organs of humans and laboratory mammals, are characterized by a small cell body and extremely long and thin processes. Different TC subpopulations share unique ultrastructural features, but express different markers. In the gastrointestinal (GI) tract, cells with features of TC were seen to be CD34-positive/c-kit-negative and several roles have been proposed for them. Other interstitial cell types with regulatory roles described in the gut are the c-kit-positive/CD34-negative/platelet-derived growth factor receptor α (PDGFRα)-negative interstitial cells of Cajal (ICC) and the PDGFRα-positive/c-kit-negative fibroblast-like cells (FLC). As TC display the same features and locations of the PDGFRα-positive cells, we investigated whether TC and PDGFRα-positive cells could be the same cell type. PDGFRα/CD34, PDGFRα/c-kit and CD34/c-kit double immunolabelling was performed in full-thickness specimens from human oesophagus, stomach and small and large intestines. All TC in the mucosa, submucosa and muscle coat were PDGFRα/CD34-positive. TC formed a three-dimensional network in the submucosa and in the interstitium between muscle layers, and an almost continuous layer at the submucosal borders of muscularis mucosae and circular muscle layer. Moreover, TC encircled muscle bundles, nerve structures, blood vessels, funds of gastric glands and intestinal crypts. Some TC were located within the muscle bundles, displaying the same location of ICC and running intermingled with them. ICC were c-kit-positive and CD34/PDGFRα-negative. In conclusion, in the human GI tract the TC are PDGFRα-positive and, therefore, might correspond to the FLC. We also hypothesize that in human gut, there are different TC subpopulations probably playing region-specific roles.

Interstitial cells of Cajal and telocytes in the gut: twins, related or simply neighbor cells?

“…Moreover, in this study, and in several others, it was demonstrated that none of the CD34 and PDGFRα + cells were c-Kit labeled, definitively excluding that these cells are ICC (50)(51)(52)(53)(54)(55) (Figure 4). Notably, while in these reports (54,55) some cells located in the axes of the villi were PDGFRα + , Vannucchi et al (51) could not find any CD34 positive cells at this level. Under TEM, cells with the features of TC were described in the axes of the villi and called myoid cells (56)(57)(58).…”

“…Recently, by using the PDGFRα antibody, cells sharing the same distribution of the CD34 positive cells were identified (51)(52)(53)(54)(55). The PDGF/PDGF receptor signaling pathway plays critical roles in mammalian organogenesis and murine GI villous morphogenesis, and it has been demonstrated that selective inhibition of the PDGFR suppresses longitudinal smooth muscle differentiation (53).…”

Telocytes are the physiological counterpart of inflammatory fibroid polyps and PDGFRA‐mutant GISTs

“…Thus, the stromal cells we describe display characteristics typical of TCs, both morphologically and immunophenotypically. In fact, TCs are characterized by a nucleated body (whose shape varies from small oval to triangular/polygonal or large round‐to‐oval, depending on the TCs’ anatomical location) that branches out into extremely long and thin prolongations, called “telopodes”; moreover, CD34 and PDGFRA are currently considered the most reliable markers for their immunohistochemical identification 24, 29. Additionally, the cells we describe are clearly distinguishable from ICCs because of both their immunophenotype and their compartmentalization.…”

Telocytes in normal and keratoconic human cornea: an immunohistochemical and transmission electron microscopy study

“…Double immunofluorescence staining combining CD34 either with PDGFRα or c‐kit/CD117 was performed according to previously published studies 31, 32, 43. Paraffin‐embedded corneal tissue sections (5 μm thick) were deparaffinized, rehydrated and boiled for 10 min.…”