# The Telocytes in the Subepicardial Niche
## 4 Discussion
### What Are (Sub)epicardial TCs?  
Stem cells can originate from the epithelial-mesenchymal transformation (EMT) of epicardial mesothelial cells (EMCs) in the adult human heart [46; 47]. Epicardium-derived cells (EPDCs) are known to express CD117/c-kit [46], which matches with our results. Immunofluorescence of the ICLCs found subepicardial TCs immediately beneath the CD34-positive epicardial mesothelium, which were either CD34-positive/c-kit-positive or purely c-kit-positive [10]. It appears that subepicardial ICLCs/TCs are EPDCs. This is reinforced by our discovery of proliferative immediate submesothelial Ki-67-positive spindle-shaped cells. Such submesothelial ICLCs were further documented through transmission electron microscopy (TEM) by the same research group; beneath them, 'isolated smooth muscle cells' were found [29]. In that study [29], subepicardial ICLCs were speculated through TEM without the aid of any antibodies. Further studies of the subepicardial niche were performed by [PERSON] et al., who reported an enlarged panel of markers useful for the identification of subepicardial TCs, such as vimentin, S100 protein, tau protein, CD57 and nestin [27]. This last antibody was listed in the report's Materials and Methods section but was not documented in the Results section of that article [27]. A polyclonal antibody was then used against CD117/c-kit [27], but that immunohistochemical method included an antigen retrieval stage (though this procedure may produce nonspecific staining results) [48]. Completely and nonspecifically stained slides were then used to sample the findings on the subepicardial TCs (Figure 6), so the respective evidence could not convince. This is demonstrative of the highly subjective manner in which TCs were assigned molecular phenotypes in the past. As we discussed previously, a lack of evidence for telepodes does not exclude the possibility of a TC morphology being present [20]. Notably, the possible expression of tau protein in TCs was speculated (Figure 6) but not discussed further in that study [27], although the presence of this protein would have indicated the presence of microtubular content in TCs. This, in turn, may have been perplexing; when this research team identified the ultrastructural anatomy of TCs [1], microtubules were not listed.  
In another study, epicardial ICLCs were found to be positive for c-kit and/or CD34, or they co-expressed c-kit and vimentin [10]. In a subsequent study, epicardial TCs were found to co-express either c-kit and CD34 or c-kit and vimentin [27]. In both these studies, [PERSON] et al. did not examine the epicardial expressions of lymphatic markers, mast cell markers or CD45. The expression of c-kit combined with the expressions of well-known endothelial markers, such as CD34 and vimentin, could not exclude TCs from the possibility of being of the endothelial lineage. It was suggested to use CD31 to discriminate the endothelial cells from TCs [49]. We also noted the striking histological resemblance of c-kit-positive epicardial 'telocytes' (Figure 2B in [27]) to c-kit-positive mast cells (Figure 1D in [50]). Both appear as large and degranulating cells. All these observations support recent and consistent evidence for TCs' failure to be categorized as a distinctive cell type [11; 24; 26].