Are telocytes related to maintenance of vascular homeostasis in normal and pathological aorta?

The telocyte (TC) is a new interstitial cell type described in a wide variety of organs and loose connective tissues around small vessels, but its presence in large arteries remains unexplored. TCs have small cell bodies and remarkably thin, long, moniliform processes called telopods (Tps). Using transmission electron microscopy and immunofluorescence, we identified TCs in normal human thoracic aortas and in those with aneurysm or acute dissection (TAAD). In normal aortas the TCs were distributed throughout the connective tissue of the adventitial layer, in its innermost portion and at the zone of transition with the medial layer, with their long axes oriented parallel to the external elastic lamellae, forming a three-dimensional network, without prevalence in the media layer. In contrast, TAAD TCs were present in the medial layer and in regions of neovascularization. The most important feature of the adventitia of diseased aortas was the presence of numerous contacts between TCs and stem cells, including vascular progenitor cells. Although the biologically functional correlations need to be elucidated, the morphological observations presented here provide strong evidence of the involvement of TCs in maintaining vascular homeostasis in pathological situations of tissue injury.

Cardiac telocytes exist in the adult Xenopus tropicalis heart.

Recent research has revealed that cardiac telocytes (CTs) play an important role in cardiac physiopathology and the regeneration of injured myocardium. Recently, we reported that the adult Xenopus tropicalis heart can regenerate perfectly in a nearly scar-free manner after injury via apical resection. However, whether telocytes exist in the X tropicalis heart and are affected in the regeneration of injured X tropicalis myocardium is still unknown. The present ultrastructural and immunofluorescent double staining results clearly showed that CTs exist in the X tropicalis myocardium. CTs in the X tropicalis myocardium were mainly twined around the surface of cardiomyocyte trabeculae and linked via nanocontacts between the ends of the telopodes, forming a three-dimensional network. CTs might play a role in the regeneration of injured myocardium.

Telocytes constitute a widespread interstitial meshwork in the lamina propria and underlying striated muscle of human tongue.

Telocytes have recently emerged as unique interstitial cells defined by their extremely long, thin and moniliform prolongations termed telopodes. Despite growing evidence that these cells consistently reside in the stromal compartment of various organs from human beings, studies dealing with telocytes in structures of the oral cavity are scarce. Hence, the present morphologic study was undertaken to explore for the first time the presence and specific localization of telocytes within tissues of the normal human tongue, a complex muscular organ whose main functions include taste, speech, and food manipulation in the oral cavity. Telocytes were initially identified by CD34 immunostaining and confirmed by CD34/PDGFRα double immunofluorescence and transmission electron microscopy. CD34+/PDGFRα+ telocytes were organized in interstitial meshworks either in the tongue lamina propria or in the underlying striated muscle. Lingual telocytes were immunonegative for CD31, c-kit and α-SMA. Telopodes were finely distributed throughout the stromal space and concentrated beneath the lingual epithelium and around CD31+ vessels, skeletal muscle bundles/fibers, and intramuscular nerves and ganglia. They also enveloped salivary gland units outside the α-SMA+ myoepithelial cells and delimited lymphoid aggregates. These findings establish telocytes as a previously overlooked interstitial cell population worth investigating further in the setting of human tongue pathophysiology.

The roles of telocytes in lung development and angiogenesis: An immunohistochemical, ultrastructural, scanning electron microscopy and morphometrical study.

Many studies have been carried out to investigate the occurrence and distribution of telocytes (TCs) in many organs. However, their morphological development is still unclear. This study was performed to demonstrate the morphological development of TCs in rabbits' lung from fetal to postnatal life using light-, electron- microscopy, immunohistochemistry, morphometrical and statistical analysis. During the fetal life, these cells formed an extensive network of telopodes (Tps) which were in close contact with developing alveoli, bronchioles, stem cells and many other interstitial components. In addition, the TCs' number was significantly increased around the neocapillaries in fetal lung. In the fetal life, TCs were stellate in shape and characterized by large cell bodies and many short Tps that contained abundant rER, mitochondria, and ribosomes. By gradual increasing of ages, TCs were spindle in shape with two Tps contained a massive amount of secretory structures (exosomes, ectosomes, and multivesicular bodies). Moreover, TCs in postnatal lung showed a significant decrease in number and diameter of their cell bodies and a significant increase in the length of Tps compared with those in fetal life. The TCs contributed with pneumocytes and endothelium in the formation of air-blood barrier. The TCs' immunohistochemical profiles for CD34, vimentin, c-kit, connexin 43, vascular endothelial growth factor (VEGF), and neuron- specific enolase (NSE) differed between ages during the lung development. This study provided an evidence that TCs contributed to angiogenesis, the formation of the air-blood barrier, lung organization, and development.

What podoplanin tells us about cells with telopodes.

Telocytes (TCs) are stromal cells with telopodes, which represent long, thin, moniliform cell processes; however, this morphological feature alone is insufficient to define a cell type. Specific markers of lymphatic endothelial cells (LECs), such as Prox-1, podoplanin (D2-40) or LYVE-1, are not usually tested in TCs. We thus aimed at performing a study in light microscopy to evaluate whether or not LECs could be mistaken for TCs. Therefore we used CD34, α-smooth muscle actin and D2-40 for an immunohistochemical study on archived paraffin-embedded samples of uterine leiomyoma. Lymphatic vessels were identified by the expression of D2-40, but on the microscopic slides, false spindle-shaped TCs appearances either corresponded to collapsed lymphatic lumina or were determined by grazing longitudinal cuts of lymphatics. It is therefore mandatory to check the expression of lymphatic markers in telocyte-like cells and, moreover, to carefully examine the bidimensional cuts in order to avoid false results.

Ultrastructural and Immunohistochemical Features of Telocytes in Placental Villi in Preeclampsia.

A new cell type, interstitial Cajal-like cell (ICLC), was recently described in different organs. The name was recently changed to telocytes (TCs), and their typical thin, long processes have been named telopodes (Tp). TCs regulate the contractile activity of smooth muscle cells and play a role in regulating vessel contractions. Although the placenta is not an innervated organ, we believe that TCs are present in the placenta. We studied placenta samples from physiological pregnancies and in different variants of preeclampsia (PE). We examined these samples using light microscopy of semi-thin sections, transmission electron microscopy, and immunohistochemistry. Immunohistochemical examination was performed with primary antibodies to CD34, CD117, SMA, and vimentin, and TMEM16a (DOG-1), the latter was used for the diagnosis of gastrointestinal stromal tumours (GIST) consisting of TCs. We have identified a heterogenetic population of ТСs in term placentas, as these cell types differed in their localization, immunophenotype and ultrastructural characteristics. We assume TMEM16a could be used as the marker for identification of TCs. In PE we have revealed telocyte-like cells with ultrastructural signs of fibrocytes (significant process thickening and the granular endoplasmic reticulum content was increased) and a loss of TMEM16a immunohistochemical staining.

Ultrastructure damage of oviduct telocytes in rat model of acute salpingitis.

Acute salpingitis (AS) is an inflammatory disease which causes severe damage to a subset of classically described cells lining in oviduct wall and contributes to interstitial fibrosis and fertility problems. Telocytes (TCs), a newly discovered peculiar type of stromal cells, have been identified in many organs, including oviduct, with proposed multiple potential bio-functions. However, with recent increasing reports regarding TCs alterations in disease-affected tissues, there is still lack of evidence about TCs involvement in AS-affected oviduct tissues and potential pathophysiological roles. We presently identified normal TCs by their characteristic ultrastructural features and immunophenotype. However, in AS-affected oviduct tissues, TCs displayed multiple ultrastructural damage both in cellular body and prolongations, with obvious loss of TCs and development of tissue fibrosis. Furthermore, TCs lose their interstitial 3-D network connected by homocellular or heterocellular junctions between TCs and adjacent cells. And especially, TCs connected to the activated immunocytes (mononuclear cells, eosinophils) and affected local immune state (repression or activation). Meanwhile, massive neutrophils infiltration and overproduced Inducible Nitric Oxide Synthase (iNOS), COX-2, suggested mechanism of inflammatory-induced TCs damage. Consequently, TCs damage might contribute to AS-induced structural and reproductive functional abnormalities of oviduct, probably via: (i) substances, energy and functional insufficiency, presumably, e.g. TC-specific genetic material profiles, ion channels, cytoskeletal elements, Tps dynamics, etc., (ii) impaired TCs-mediated multicellular signalling, such as homeostasis/angiogenesis, tissue repair/regeneration, neurotransmission, (iii) derangement of 3-D network and impaired mechanical support for TCs-mediated multicellular signals within the stromal compartment, consequently induced interstitial fibrosis, (iv) involvement in local inflammatory process/ immunoregulation and possibly immune-mediated early pregnancy failure.