**2. Gastrointestinal tract**

*Innovations in Cell Research and Therapy*

especially because no specific immunomarkers are available [28]. Indeed, the cell surface glycoprotein CD34, a marker shared with vascular endothelial cells, is currently considered one of the most suitable for the immunohistochemical identification of the TCs, which are also referred to as CD34+ stromal cells/TCs by some authors [29, 30]. Through extensive homo-cellular networks, TCs are believed to build the stromal scaffold whose continuity and adaptability guarantees the maintenance of the integrity of tissues/organs every time they are subjected to mechanical forces, such as distension and stretching. Moreover, TCs are universally considered key organizers of the connective tissue and eventually, they may contribute to the production and shaping of the extracellular matrix (ECM) in cooperation with fibroblasts. This has been observed in TCs located in the female genital tract where these cells express both estrogen and progesterone receptors [4, 31] whose activation is followed by significant changes of the TCs that acquire fibroblast-like features and become capable to produce the ECM [8]. Likely, the homo-cellular TCs contacts are also involved in the intercellular exchange of molecular or ionic signaling. Alongside the aforementioned roles, probably shared by all the TCs, many other roles have been attributed to these cells [30]. Therefore, each of the TCs subtypes is likely to play its organ-/tissue-specific

Although the TCs homo-cellular contacts are commonly observed, a variety of cell-to-cell contacts between TCs and other cell types (referred to as heterocellular contacts) are also observed [8, 32–35]. They consist of minute junctions (point contacts, nanocontacts, and planar contacts) whose mean inter-membrane distance is 10–30 nm, but more often by variably extended simple apposition of the contiguous plasma membranes that might act either as mechanical cell-to-cell attachments or as sites of intercellular communication [18]. Among these contacts, there are the so-called "stromal synapses" [36], a term used to describe those contacts occurring between TCs and several types of connective tissue cells such as mast cells, macrophages, myofibroblasts, and fibroblasts [8, 18, 35, 37]. The networks built by these hetero-cellular contacts are named "mixed networks." Collectively, the existence of mixed networks in addition to the homo-cellular TCs networks, the morphological and immunohistochemical differences reported for the TCs among organs and tissues, the existence of TCs subtypes, the interactions that TCs make with the ECM and, finally, the TCs vicinity to nerve endings and vascular cells, have substantiated the hypothesis that these cells may be part of integrated systems playing tissue-/organ-specific

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role [8].

roles [8, 30, 32, 33, 35, 38].

well as from tissue-resident stem cells.

**1.2 Specific roles of the telocyte network: hollow organs**

A common role proposed for the 3-D TCs scaffold in the hollow organs is to follow organ distension and relaxation avoiding anomalous deformation and controlling blood vessels closure or rheology. However, because of the anatomical complexity of such districts and the great variety of cell populations herein interacting with the TCs, many other roles are conceivable, suggesting that these cells, as connecting devices in the stromal space, might take center stage in the integration of all the information coming from the vascular, nervous, and immune systems, as

The present overview of the literature focused on the spatial organization, morphological, and histochemical peculiarities of the TCs, according to their location in different organs. This may help to point out the presumptive roles of the homo- and hetero-cellular TCs networks. With this aim, the TCs networks located in some representative hollow organs that have been more intensively studied, such as the

The gastrointestinal tract consists of different hollow organs which have some similar and some different shapes and functions. Every organ modifies its lumen caliber and thickness several times throughout the day, following food transit. Food intake might happen several times per day, with different types and quantities, and the food transit varies according to the different regions, from the stomach to the colon. The cells of the lining epithelium do not change their shape, while microvilli height importantly changes. Under the mucosa, made by the epithelium, the lamina propria, and the muscular mucosae, there is the submucosa that has different morphological organization and function. Finally, the muscle coat is responsible for gastrointestinal contractility. Two motile activities, coordinated by the enteric nervous system and the ICCs, are present: peristalsis, a constant ab-oral movement that does not importantly modify the lumen caliber, and the relaxation/contraction related to food arrival/mixing for digestion and absorption/transit which promotes sustained lumen caliber changes. Region-specific mechanical and functional interrelationships between all the components of this complex apparatus are at the basis of the correct and coordinated behavior of the apparatus.
