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Telocytes and Other Interstitial Cells 2.0: From Structure to Function
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Telocytes and Other Interstitial Cells 2.0: From Structure to Function

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (15 May 2022) | Viewed by 16006

Special Issue Editor

Dr. Sanda M. Cretoiu

E-Mail Website
Guest Editor
Department of Cellular and Molecular Medicine, 'Carol Davila' University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania
Interests: interstitial cells; tissue remodelling; intercellular signalling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue “Telocytes and Other Interstitial Cells: From Structure to Function”.

Interstitial cells are seen as any of the many cells that lies in connective tissue, filling the spaces between the functional tissue of an organ (parenchyma). Cells that use the name interstitial are found in many locations, such as the seminiferous tubules of the testes, and ovaries, the medulla and cortex of the kidney, etc. Moreover, in this category, we also include the interstitial cells of Cajal.

In recent years, special attention has been given to the telocytes, formerly known as interstitial Cajal-like cells. Telocytes represent a particular type of interstitial cells, seen as “connecting devices” integrating the overall information from the vascular, nervous and immune system, interstitium, and stem cells.

This Special Issue is devoted to recent progress in research onto interstitial cells in general. It also aims to form an opinion on the controversial role of telocytes and especially to see them integrated in the context of the concept of interstitial cells.

Outstanding experts interested in this thematic issue are very welcome to send original manuscripts and reviews dealing with any of the abovementioned cells.

Dr. Sanda M. Cretoiu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • interstitial cells
  • interstitial cells of Cajal
  • telocytes
  • intercellular communication
  • extracellular vesicles

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Published Papers (18 papers)

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Editorial

Jump to: Research, Review

3 pages, 200 KiB  
Editorial
Telocytes and Other Interstitial Cells 2.0: From Structure to Function
by Sanda Maria Cretoiu
Int. J. Mol. Sci. 2022, 23(24), 16221; https://doi.org/10.3390/ijms232416221 - 19 Dec 2022
Cited by 1 | Viewed by 1058
Abstract
Interstitial cells are often seen as those cells that fill the space between parenchymal cells, responsible for fulfilling the function of an organ [...] Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells 2.0: From Structure to Function)
3 pages, 173 KiB  
Editorial
Telocytes and Other Interstitial Cells: From Structure to Function
by Sanda Maria Crețoiu
Int. J. Mol. Sci. 2021, 22(10), 5271; https://doi.org/10.3390/ijms22105271 - 17 May 2021
Cited by 9 | Viewed by 1768
Abstract
The Special Issue, “Telocytes and Other Interstitial Cells: From Structure to Function” of the International Journal of Molecular Sciences, is dedicated to recent progress in research on interstitial cells [...] Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells: From Structure to Function)

Research

Jump to: Editorial, Review

16 pages, 6738 KiB  
Article
Scleroderma-like Impairment in the Network of Telocytes/CD34+ Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis
by Irene Rosa, Eloisa Romano, Bianca Saveria Fioretto, Daniele Guasti, Lidia Ibba-Manneschi, Marco Matucci-Cerinic and Mirko Manetti
Int. J. Mol. Sci. 2021, 22(22), 12407; https://doi.org/10.3390/ijms222212407 - 17 Nov 2021
Cited by 8 | Viewed by 2342
Abstract
Considerable evidence accumulated over the past decade supports that telocytes (TCs)/CD34+ stromal cells represent an exclusive type of interstitial cells identifiable by transmission electron microscopy (TEM) or immunohistochemistry in various organs of the human body, including the skin. By means of their [...] Read more.
Considerable evidence accumulated over the past decade supports that telocytes (TCs)/CD34+ stromal cells represent an exclusive type of interstitial cells identifiable by transmission electron microscopy (TEM) or immunohistochemistry in various organs of the human body, including the skin. By means of their characteristic cellular extensions (telopodes), dermal TCs are arranged in networks intermingled with a multitude of neighboring cells and, hence, they are thought to contribute to skin homeostasis through both intercellular contacts and releasing extracellular vesicles. In this context, fibrotic skin lesions from patients with systemic sclerosis (SSc, scleroderma) appear to be characterized by a disruption of the dermal network of TCs, which has been ascribed to either cell degenerative processes or possible transformation into profibrotic myofibroblasts. In the present study, we utilized the well-established mouse model of bleomycin-induced scleroderma to gain further insights into the TC alterations found in cutaneous fibrosis. CD34 immunofluorescence revealed a severe impairment in the dermal network of TCs/CD34+ stromal cells in bleomycin-treated mice. CD31/CD34 double immunofluorescence confirmed that CD31−/CD34+ TC counts were greatly reduced in the skin of bleomycin-treated mice compared with control mice. Ultrastructural signs of TC injury were detected in the skin of bleomycin-treated mice by TEM. The analyses of skin samples from mice treated with bleomycin for different times by either TEM or double immunostaining and immunoblotting for the CD34/α-SMA antigens collectively suggested that, although a few TCs may transition to α-SMA+ myofibroblasts in the early disease stage, most of these cells rather undergo degeneration, and then are lost. Taken together, our data demonstrate that TC changes in the skin of bleomycin-treated mice mimic very closely those observed in human SSc skin, which makes this experimental model a suitable tool to (i) unravel the pathological mechanisms underlying TC damage and (ii) clarify the possible contribution of the TC loss to the development/progression of dermal fibrosis. In perspective, these findings may have important implications in the field of skin regenerative medicine. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells 2.0: From Structure to Function)
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15 pages, 3221 KiB  
Article
Hypoxic Culture Maintains Cell Growth of the Primary Human Valve Interstitial Cells with Stemness
by Kaho Kanno, Tomohisa Sakaue, Mika Hamaguchi, Kenji Namiguchi, Daisuke Nanba, Jun Aono, Mie Kurata, Junya Masumoto, Shigeki Higashiyama and Hironori Izutani
Int. J. Mol. Sci. 2021, 22(19), 10534; https://doi.org/10.3390/ijms221910534 - 29 Sep 2021
Cited by 7 | Viewed by 2441
Abstract
The characterization of aortic valve interstitial cells (VICs) cultured under optimal conditions is essential for understanding the molecular mechanisms underlying aortic valve stenosis. Here, we propose 2% hypoxia as an optimum VIC culture condition. Leaflets harvested from patients with aortic valve regurgitation were [...] Read more.
The characterization of aortic valve interstitial cells (VICs) cultured under optimal conditions is essential for understanding the molecular mechanisms underlying aortic valve stenosis. Here, we propose 2% hypoxia as an optimum VIC culture condition. Leaflets harvested from patients with aortic valve regurgitation were digested using collagenase and VICs were cultured under the 2% hypoxic condition. A significant increase in VIC growth was observed in 2% hypoxia (hypo-VICs), compared to normoxia (normo-VICs). RNA-sequencing revealed that downregulation of oxidative stress-marker genes (such as superoxide dismutase) and upregulation of cell cycle accelerators (such as cyclins) occurred in hypo-VICs. Accumulation of reactive oxygen species was observed in normo-VICs, indicating that low oxygen tension can avoid oxidative stress with cell-cycle arrest. Further mRNA quantifications revealed significant upregulation of several mesenchymal and hematopoietic progenitor markers, including CD34, in hypo-VICs. The stemness of hypo-VICs was confirmed using osteoblast differentiation assays, indicating that hypoxic culture is beneficial for maintaining growth and stemness, as well as for avoiding senescence via oxidative stress. The availability of hypoxic culture was also demonstrated in the molecular screening using proteomics. Therefore, hypoxic culture can be helpful for the identification of therapeutic targets and the evaluation of VIC molecular functions in vitro. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells 2.0: From Structure to Function)
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13 pages, 3391 KiB  
Article
Identification of CD34+/PGDFRα+ Valve Interstitial Cells (VICs) in Human Aortic Valves: Association of Their Abundance, Morphology and Spatial Organization with Early Calcific Remodeling
by Grzegorz J. Lis, Andrzej Dubrowski, Maciej Lis, Bernard Solewski, Karolina Witkowska, Veronika Aleksandrovych, Ewa Jasek-Gajda, Mateusz K. Hołda, Krzysztof Gil and Jan A. Litwin
Int. J. Mol. Sci. 2020, 21(17), 6330; https://doi.org/10.3390/ijms21176330 - 31 Aug 2020
Cited by 11 | Viewed by 2825
Abstract
Aortic valve interstitial cells (VICs) constitute a heterogeneous population involved in the maintenance of unique valvular architecture, ensuring proper hemodynamic function but also engaged in valve degeneration. Recently, cells similar to telocytes/interstitial Cajal-like cells described in various organs were found in heart valves. [...] Read more.
Aortic valve interstitial cells (VICs) constitute a heterogeneous population involved in the maintenance of unique valvular architecture, ensuring proper hemodynamic function but also engaged in valve degeneration. Recently, cells similar to telocytes/interstitial Cajal-like cells described in various organs were found in heart valves. The aim of this study was to examine the density, distribution, and spatial organization of a VIC subset co-expressing CD34 and PDGFRα in normal aortic valves and to investigate if these cells are associated with the occurrence of early signs of valve calcific remodeling. We examined 28 human aortic valves obtained upon autopsy. General valve morphology and the early signs of degeneration were assessed histochemically. The studied VICs were identified by immunofluorescence (CD34, PDGFRα, vimentin), and their number in standardized parts and layers of the valves was evaluated. In order to show the complex three-dimensional structure of CD34+/PDGFRα+ VICs, whole-mount specimens were imaged by confocal microscopy, and subsequently rendered using the Imaris (Bitplane AG, Zürich, Switzerland) software. CD34+/PDGFRα+ VICs were found in all examined valves, showing significant differences in the number, distribution within valve tissue, spatial organization, and morphology (spherical/oval without projections; numerous short projections; long, branching, occasionally moniliform projections). Such a complex morphology was associated with the younger age of the subjects, and these VICs were more frequent in the spongiosa layer of the valve. Both the number and percentage of CD34+/PDGFRα+ VICs were inversely correlated with the age of the subjects. Valves with histochemical signs of early calcification contained a lower number of CD34+/PDGFRα+ cells. They were less numerous in proximal parts of the cusps, i.e., areas prone to calcification. The results suggest that normal aortic valves contain a subpopulation of CD34+/PDGFRα+ VICs, which might be involved in the maintenance of local microenvironment resisting to pathologic remodeling. Their reduced number in older age could limit the self-regenerative properties of the valve stroma. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells: From Structure to Function)
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16 pages, 4109 KiB  
Article
A Two-Step Immunomagnetic Microbead-Based Method for the Isolation of Human Primary Skin Telocytes/CD34+ Stromal Cells
by Eloisa Romano, Irene Rosa, Bianca Saveria Fioretto, Elena Lucattelli, Marco Innocenti, Lidia Ibba-Manneschi, Marco Matucci-Cerinic and Mirko Manetti
Int. J. Mol. Sci. 2020, 21(16), 5877; https://doi.org/10.3390/ijms21165877 - 16 Aug 2020
Cited by 26 | Viewed by 3122
Abstract
Telocytes (TCs), commonly referred to as TCs/CD34+ stromal cells, are a peculiar type of interstitial cells with distinctive morphologic traits that are supposed to exert several biological functions, including tissue homeostasis regulation, cell-to-cell signaling, immune surveillance, and reparative/regenerative effects. At present, the majority [...] Read more.
Telocytes (TCs), commonly referred to as TCs/CD34+ stromal cells, are a peculiar type of interstitial cells with distinctive morphologic traits that are supposed to exert several biological functions, including tissue homeostasis regulation, cell-to-cell signaling, immune surveillance, and reparative/regenerative effects. At present, the majority of studies investigating these cells are mainly descriptive and focus only on their morphology, with a consequent paucity of functional data. To gain relevant insight into the possible functions of TCs, in vitro analyses are clearly required, but currently, the protocols for TC isolation are only at the early stages and not fully standardized. In the present in vitro study, we describe a novel methodology for the purification of human primary skin TCs through a two-step immunomagnetic microbead-based cell separation (i.e., negative selection for CD31 followed by positive selection for CD34) capable of discriminating these cells from other connective tissue-resident cells on the basis of their different immunophenotypic features. Our experiments clearly demonstrated that the proposed method allows a selective purification of cells exhibiting the peculiar TC morphology. Isolated TCs displayed very long cytoplasmic extensions with a moniliform silhouette (telopodes) and presented an immunophenotypic profile (CD31−/CD34+/PDGFRα+/vimentin+) that unequivocally differentiates them from endothelial cells (CD31+/CD34+/PDGFRα−/vimentin+) and fibroblasts (CD31−/CD34−/PDGFRα+/vimentin+). This novel methodology for the isolation of TCs lays the groundwork for further research aimed at elucidating their functional properties and possible translational applications, especially in the field of regenerative medicine. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells: From Structure to Function)
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23 pages, 18198 KiB  
Article
Mechanosensitivity Is a Characteristic Feature of Cultured Suburothelial Interstitial Cells of the Human Bladder
by Jochen Neuhaus, Andreas Gonsior, Sheng Cheng, Jens-Uwe Stolzenburg and Frank Peter Berger
Int. J. Mol. Sci. 2020, 21(15), 5474; https://doi.org/10.3390/ijms21155474 - 31 Jul 2020
Cited by 8 | Viewed by 2445
Abstract
Bladder dysfunction is characterized by urgency, frequency (pollakisuria, nocturia), and dysuria and may lead to urinary incontinence. Most of these symptoms can be attributed to disturbed bladder sensitivity. There is growing evidence that, besides the urothelium, suburothelial interstitial cells (suICs) are involved in [...] Read more.
Bladder dysfunction is characterized by urgency, frequency (pollakisuria, nocturia), and dysuria and may lead to urinary incontinence. Most of these symptoms can be attributed to disturbed bladder sensitivity. There is growing evidence that, besides the urothelium, suburothelial interstitial cells (suICs) are involved in bladder afferent signal processing. The massive expansion of the bladder during the filling phase implicates mechanical stress delivered to the whole bladder wall. Little is known about the reaction of suICs upon mechanical stress. Therefore, we investigated the effects of mechanical stimulation in cultured human suICs. We used fura-2 calcium imaging as a major physiological readout. We found spontaneous intracellular calcium activity in 75 % of the cultured suICs. Defined local pressure application via a glass micropipette led to local increased calcium activity in all stimulated suICs, spreading over the whole cell. A total of 51% of the neighboring cells in a radius of up to 100 µm from the stimulated cell showed an increased activity. Hypotonic ringer and shear stress also induced calcium transients. We found an 18-times increase in syncytial activity compared to unstimulated controls, resulting in an amplification of the primary calcium signal elicited in single cells by 50%. Our results speak in favor of a high sensitivity of suICs for mechanical stress and support the view of a functional syncytium between suICs, which can amplify and distribute local stimuli. Previous studies of connexin expression in the human bladder suggest that this mechanism could also be relevant in normal and pathological function of the bladder in vivo. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells: From Structure to Function)
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15 pages, 14988 KiB  
Article
Interstitial Leydig Cell Tumorigenesis—Leptin and Adiponectin Signaling in Relation to Aromatase Expression in the Human Testis
by Michal Duliban, Ewelina Gorowska-Wojtowicz, Waclaw Tworzydlo, Agnieszka Rak, Malgorzata Brzoskwinia, Izabella Krakowska, Jan K. Wolski, Malgorzata Kotula-Balak, Bartosz J. Płachno and Barbara Bilinska
Int. J. Mol. Sci. 2020, 21(10), 3649; https://doi.org/10.3390/ijms21103649 - 21 May 2020
Cited by 16 | Viewed by 3317
Abstract
Although epidemiological studies from the last years report an increase in the incidences of Leydig cell tumors (previously thought to be a rare disease), the biochemical characteristics of that tumor important for understanding its etiology, diagnosis, and therapy still remains not completely characterized. [...] Read more.
Although epidemiological studies from the last years report an increase in the incidences of Leydig cell tumors (previously thought to be a rare disease), the biochemical characteristics of that tumor important for understanding its etiology, diagnosis, and therapy still remains not completely characterized. Our prior studies reported G-protein coupled estrogen receptor signaling and estrogen level disturbances in Leydig cell tumors. In addition, we found that expressions of multi-level-acting lipid balance- and steroidogenesis–controlling proteins including peroxisome proliferator-activated receptor are altered in this tumor. In order to get deeper into the other molecular mechanisms that regulate lipid homeostasis in the Leydig cell tumor, here we investigate the presence and expression of newly-described hormones responsible for lipid homeostasis balancing (leptin and adiponectin), together with expression of estrogen synthase (aromatase). Samples of Leydig cell tumors (n = 20) were obtained from patients (31–45 years old) and used for light and transmission electron microscopic, western blotting, and immunohistochemical analyses. In addition, body mass index (BMI) was calculated. In tumor mass, abundant lipid accumulation in Leydig cells and various alterations of Leydig cell shape, as well as the presence of adipocyte-like cells, were observed. Marked lipid content and various lipid droplet size, especially in obese patients, may indicate alterations in lipid homeostasis, lipid processing, and steroidogenic organelle function in response to interstitial tissue pathological changes. We revealed significantly increased expression of leptin, adiponectin and their receptors, as well as aromatase in Leydig cell tumors in comparison to control. The majority of patients (n = 13) were overweight as indicated by their BMI. Moreover, a significant increase in expression of phospholipase C (PLC), and kinases Raf, ERK which are part of adipokine transductional pathways, was demonstrated. These data expand our previous findings suggesting that in human Leydig cell tumors, estrogen level and signaling, together with lipid status, are related to each other. Increased BMI may contribute to certain biochemical characteristics and function of the Leydig cell in infertile patients with a tumor. In addition, altered adipokine-estrogen microenvironment can have an effect on proliferation, growth, and metastasis of tumor cells. We report here various targets (receptors, enzymes, hormones) controlling lipid balance and estrogen action in Leydig cell tumors indicating their possible usefulness for diagnostics and therapy. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells: From Structure to Function)
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19 pages, 5242 KiB  
Article
Simulation and Modeling of Telocytes Behavior in Signaling and Intercellular Communication Processes
by Dragos Cretoiu, Simona Roatesi, Ion Bica, Cezar Plesca, Amado Stefan, Oana Bajenaru, Carmen Elena Condrat and Sanda Maria Cretoiu
Int. J. Mol. Sci. 2020, 21(7), 2615; https://doi.org/10.3390/ijms21072615 - 9 Apr 2020
Cited by 23 | Viewed by 2687
Abstract
Background: Telocytes (TCs) are unique interstitial or stromal cells of mesodermal origin, defined by long cellular extensions called telopodes (Tps) which form a network, connecting them to surrounding cells. TCs were previously found around stem and progenitor cells, and were thought to be [...] Read more.
Background: Telocytes (TCs) are unique interstitial or stromal cells of mesodermal origin, defined by long cellular extensions called telopodes (Tps) which form a network, connecting them to surrounding cells. TCs were previously found around stem and progenitor cells, and were thought to be most likely involved in local tissue metabolic equilibrium and regeneration. The roles of telocytes are still under scientific scrutiny, with existing studies suggesting they possess various functions depending on their location. Methods: Human myometrium biopsies were collected from pregnant and non-pregnant women, telocytes were then investigated in myometrial interstitial cell cultures based on morphological criteria and later prepared for time-lapse microscopy. Semi-analytical and numerical solutions were developed to highlight the geometric characteristics and the behavior of telocytes. Results: Results were gathered in a database which would further allow efficient telocyte tracking and indexing in a content-based image retrieval (CBIR) of digital medical images. Mathematical analysis revealed pivotal information regarding the homogeneity, hardness and resistance of telocytes’ structure. Cellular activity models were monitored in vitro, therefore supporting the creation of databases of telocyte images. Conclusions: The obtained images were analyzed, using segmentation techniques and mathematical models in conjunction with computer simulation, in order to depict TCs behavior in relation to surrounding cells. This paper brings an important contribution to the development of bioinformatics systems by creating software-based telocyte models that could be used both for diagnostic and educational purposes. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells: From Structure to Function)
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20 pages, 6547 KiB  
Article
Identification of Telocytes in the Pancreas of Turtles—A role in Cellular Communication
by Noor Samad Gandahi, Botao Ding, Yonghong Shi, Xuebing Bai, Jameel Ahmed Gandahi, Waseem Ali Vistro, Qiusheng Chen and Ping Yang
Int. J. Mol. Sci. 2020, 21(6), 2057; https://doi.org/10.3390/ijms21062057 - 17 Mar 2020
Cited by 16 | Viewed by 3339
Abstract
The existence of telocytes (TCs) has not yet been established in the pancreases of aquatic reptiles. Here, we report TCs in the exocrine pancreas of Pelodiscus sinensis using transmission electron microscope (TEM), immunohistochemistry (IHC), and immunofluorescence (IF) techniques. TCs surrounded the acini and [...] Read more.
The existence of telocytes (TCs) has not yet been established in the pancreases of aquatic reptiles. Here, we report TCs in the exocrine pancreas of Pelodiscus sinensis using transmission electron microscope (TEM), immunohistochemistry (IHC), and immunofluorescence (IF) techniques. TCs surrounded the acini and ducts of the connective tissue of the exocrine pancreas and between lobules and gland cells. The cells were located preferably close to the blood vessels, interlobular ducts, and nerve fibers. Ultrastructurally, TCs exhibited small and large bodies with thick and thin portions, podoms, and podomers, and prolongations that form dichotomous branching with hetero-cellular and homo-cellular junctions. The podom (thick) portions showed caveolae, mitochondria, rough endoplasmic reticulum, and vesicles. The nucleus carries heterochromatin and is irregular in shape. The shape of TCs depends on the number of telopodes (Tps) bearing long, short, spindle, triangular, and “beads on a string” shapes with twisted, tortuous prolongations and ramifications. Shed extracellular vesicles and exosomes were found frequently released from projections and Tps within connective tissue in the vicinity of the acini and collagen fibers. IHC and IF results showed CD34+, α-SMA+, and vimentin+, long and triangle-shaped TCs, consistent with the TEM findings. The presence of shaded vesicles from TCs might implicate their possible role in immune surveillance, tissue regeneration as well as regulatory functions in the reptilian pancreas. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells: From Structure to Function)
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Review

Jump to: Editorial, Research

13 pages, 807 KiB  
Review
Behavior and Functional Roles of CD34+ Mesenchymal Cells in Mammalian Testes
by Shin-ichi Abe
Int. J. Mol. Sci. 2022, 23(17), 9585; https://doi.org/10.3390/ijms23179585 - 24 Aug 2022
Cited by 4 | Viewed by 1728
Abstract
Mammalian testes consist of seminiferous tubules within which Sertoli cells line up at the periphery and nurse germ cells, and of interstitia that harbor various cells such as peritubular myoid cells (PMCs), Leydig cells (LCs), vascular endothelial cells, immune cells such as macrophages, [...] Read more.
Mammalian testes consist of seminiferous tubules within which Sertoli cells line up at the periphery and nurse germ cells, and of interstitia that harbor various cells such as peritubular myoid cells (PMCs), Leydig cells (LCs), vascular endothelial cells, immune cells such as macrophages, and mesenchymal (stromal) cells. Morphological studies have recently reported the presence of telocytes with telopodes in the interstitium of adult mouse, rat, and human testes. CD34+PDGFRα+ telocytes with long and moniliform telopodes form reticular networks with various cell types such as LCs, PMCs, and vessels, indicating their potential functions in cell–cell communications and tissue homeostasis. Functional studies have recently been performed on testicular interstitial cells and CD34+ cells, using 3D re-aggregate cultures of dissociated testicular cells, and cell cultures. Direct observation of CD34+ cells and adult LCs (ALCs) revealed that CD34+ cells extend thin cytoplasmic processes (telopodes), move toward the LC–CD34+ cell-re-aggregates, and finally enter into the re-aggregates, indicating the chemotactic behavior of CD34+ telocytes toward ALCs. In mammalian testes, important roles of mesenchymal interstitial cells as stem/progenitors in the differentiation and regeneration of LCs have been reported. Here, reports on testicular telocytes so far obtained are reviewed, and future perspectives on the studies of testicular telocytes are noted. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells 2.0: From Structure to Function)
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12 pages, 20397 KiB  
Review
Telocytes and Macrophages in the Gut: From Morphology to Function, Do the Two Cell Types Interact with Each Other? Which Helps Which?
by Maria Giuliana Vannucchi
Int. J. Mol. Sci. 2022, 23(15), 8435; https://doi.org/10.3390/ijms23158435 - 29 Jul 2022
Cited by 3 | Viewed by 1644
Abstract
Telocytes and macrophages are ubiquitous cells located in loose connective tissues and share the same mesenchymal origin. Despite these common elements, depending on where they reside, these two cell types are profoundly different in terms of their morphology and functions. The purpose of [...] Read more.
Telocytes and macrophages are ubiquitous cells located in loose connective tissues and share the same mesenchymal origin. Despite these common elements, depending on where they reside, these two cell types are profoundly different in terms of their morphology and functions. The purpose of this review is to provide an update on the knowledge regarding telocytes and macrophages in the gut, where their presence and significance have long been underestimated or misunderstood. The focus will be on the possibility that these two cell types interact with each other and on the potential meaning of these interactions. Based on the complexity of the topic, the variety of possible methodological approaches and the expertise of the author, the point of view in the discussion of the literature data will be mainly morphological. Furthermore, considering the relatively recent period in which these cell types have acquired a primary role in gastrointestinal functions, the attention will be greatly confined to those articles published in the last decade. The microbiota, another main protagonist in this context, will be mentioned only in passing. It is hoped that this review, although not exhaustive, will highlight the importance of macrophages and telocytes in the complex mechanisms that ensure intestinal functions. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells 2.0: From Structure to Function)
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14 pages, 2816 KiB  
Review
Telocytes’ Role in Modulating Gut Motility Function and Development: Medical Hypotheses and Literature Review
by Daniel Dumitru Banciu, Dragoș Crețoiu, Sanda Maria Crețoiu, Adela Banciu, Daniel Popa, Rodica David, Cristian Stefan Berghea-Neamtu, Calin Remus Cipaian, Mihai Octavian Negrea, Mihaela Gheonea and Bogdan Neamtu
Int. J. Mol. Sci. 2022, 23(13), 7017; https://doi.org/10.3390/ijms23137017 - 24 Jun 2022
Cited by 6 | Viewed by 2349
Abstract
This review article explores the telocytes’ roles in inflammatory bowel diseases (IBD), presenting the mechanisms and hypotheses related to epithelial regeneration, progressive fibrosis, and dysmotility as a consequence of TCs’ reduced or absent number. Based on the presented mechanisms and hypotheses, we aim [...] Read more.
This review article explores the telocytes’ roles in inflammatory bowel diseases (IBD), presenting the mechanisms and hypotheses related to epithelial regeneration, progressive fibrosis, and dysmotility as a consequence of TCs’ reduced or absent number. Based on the presented mechanisms and hypotheses, we aim to provide a functional model to illustrate TCs’ possible roles in the normal and pathological functioning of the digestive tract. TCs are influenced by the compression of nearby blood vessels and the degree of fibrosis of the surrounding tissues and mediate these processes in response. The changes in intestinal tube vascularization induced by the movement of the food bowl, and the consequent pH changes that show an anisotropy in the thickness of the intestinal tube wall, have led to the identification of a pattern of intestinal tube development based on telocytes’ ability to communicate and modulate surrounding cell functions. In the construction of the theoretical model, given the predictable occurrence of colic in the infant, the two-layer arrangement of the nerve plexuses associated with the intestinal tube was considered to be incompletely adapted to the motility required with a diversified diet. There is resulting evidence of possible therapeutic targets for diseases associated with changes in local nerve tissue development. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells 2.0: From Structure to Function)
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11 pages, 644 KiB  
Review
Cardiac Telocytes 16 Years on—What Have We Learned So Far, and How Close Are We to Routine Application of the Knowledge in Cardiovascular Regenerative Medicine?
by Martin Klein, Mária Csöbönyeiová, Stanislav Žiaran, Ľuboš Danišovič and Ivan Varga
Int. J. Mol. Sci. 2021, 22(20), 10942; https://doi.org/10.3390/ijms222010942 - 10 Oct 2021
Cited by 10 | Viewed by 2883
Abstract
The regeneration of a diseased heart is one of the principal challenges of modern cardiovascular medicine. There has been ongoing research on stem-cell-based therapeutic approaches. A cell population called telocytes (TCs) described only 16 years ago largely contributed to the research area of [...] Read more.
The regeneration of a diseased heart is one of the principal challenges of modern cardiovascular medicine. There has been ongoing research on stem-cell-based therapeutic approaches. A cell population called telocytes (TCs) described only 16 years ago largely contributed to the research area of cardiovascular regeneration. TCs are cells with small bodies and extremely long cytoplasmic projections called telopodes, described in all layers of the heart wall. Their functions include cell-to-cell signaling, stem-cell nursing, mechanical support, and immunoregulation, to name but a few. The functional derangement or quantitative loss of TCs has been implicated in the pathogenesis of myocardial infarction, heart failure, arrhythmias, and many other conditions. The exact pathomechanisms are still unknown, but the loss of regulative, integrative, and nursing functions of TCs may provide important clues. Therefore, a viable avenue in the future modern management of these conditions is TC-based cell therapy. TCs have been previously transplanted into a mouse model of myocardial infarction with promising results. Tandem transplantation with stem cells may provide additional benefit; however, many underresearched areas need to be addressed in future research before routine application of TC-based cell therapy in human subjects. These include the standardization of protocols for isolation, cultivation, and transplantation, quantitative optimization of TC transplants, cost-effectivity analysis, and many others. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells 2.0: From Structure to Function)
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19 pages, 6445 KiB  
Review
Telocytes/CD34+ Stromal Cells in Pathologically Affected White Adipose Tissue
by Lucio Díaz-Flores, Ricardo Gutiérrez, Ma Pino García, Miriam González-Gómez, Jose Luís Carrasco, Hugo Alvarez-Argüelles and Lucio Díaz-Flores, Jr.
Int. J. Mol. Sci. 2020, 21(24), 9694; https://doi.org/10.3390/ijms21249694 - 18 Dec 2020
Cited by 16 | Viewed by 2628
Abstract
We studied telocytes/CD34+ stromal cells (TCs/CD34+SCs) in pathologically affected white adipose tissue after briefly examining them in normal fat. To this aim, we reviewed pathological processes, including original contributions, in which TCs/CD34+SCs are conserved, increased, and lost, or acquire a specific arrangement. The [...] Read more.
We studied telocytes/CD34+ stromal cells (TCs/CD34+SCs) in pathologically affected white adipose tissue after briefly examining them in normal fat. To this aim, we reviewed pathological processes, including original contributions, in which TCs/CD34+SCs are conserved, increased, and lost, or acquire a specific arrangement. The pathologic processes in which TCs/CD34+SCs are studied in adipose tissue include inflammation and repair through granulation tissue, iatrogenic insulin-amyloid type amyloidosis, non-adipose tissue components (nerve fascicles and fibres in neuromas and hyperplastic neurogenic processes) and tumours (signet ring carcinoma with Krukenberg tumour and colon carcinoma) growing in adipose tissue, adipose tissue tumours (spindle cell lipoma, dendritic fibromyxolipoma, pleomorphic lipoma, infiltrating angiolipoma of skeletal muscle and elastofibrolipoma), lipomatous hypertrophy of the interatrial septum, nevus lipomatosus cutaneous superficialis of Hoffman–Zurhelle and irradiated adipose tissue of the perirectal and thymic regions. Two highly interesting issues emerged: (1) whether the loss of CD34 expression in TCs/CD34+SCs is by changes in marker expression or the disappearance of these cells (the findings suggest the first possibility) and (2) whether in some invasive and metastatic malignant tumours, TCs/CD34+SCs that completely surround neoplastic cells act as nurse and/or isolating cells. Further studies are required on adipose tissue TCs/CD34+SCs, mainly in lipomatosis and obesity. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells: From Structure to Function)
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18 pages, 1085 KiB  
Review
Understanding the Biology of Human Interstitial Cells of Cajal in Gastrointestinal Motility
by Daphne Foong, Jerry Zhou, Ali Zarrouk, Vincent Ho and Michael D. O’Connor
Int. J. Mol. Sci. 2020, 21(12), 4540; https://doi.org/10.3390/ijms21124540 - 25 Jun 2020
Cited by 61 | Viewed by 7101
Abstract
Millions of patients worldwide suffer from gastrointestinal (GI) motility disorders such as gastroparesis. These disorders typically include debilitating symptoms, such as chronic nausea and vomiting. As no cures are currently available, clinical care is limited to symptom management, while the underlying causes of [...] Read more.
Millions of patients worldwide suffer from gastrointestinal (GI) motility disorders such as gastroparesis. These disorders typically include debilitating symptoms, such as chronic nausea and vomiting. As no cures are currently available, clinical care is limited to symptom management, while the underlying causes of impaired GI motility remain unaddressed. The efficient movement of contents through the GI tract is facilitated by peristalsis. These rhythmic slow waves of GI muscle contraction are mediated by several cell types, including smooth muscle cells, enteric neurons, telocytes, and specialised gut pacemaker cells called interstitial cells of Cajal (ICC). As ICC dysfunction or loss has been implicated in several GI motility disorders, ICC represent a potentially valuable therapeutic target. Due to their availability, murine ICC have been extensively studied at the molecular level using both normal and diseased GI tissue. In contrast, relatively little is known about the biology of human ICC or their involvement in GI disease pathogenesis. Here, we demonstrate human gastric tissue as a source of primary human cells with ICC phenotype. Further characterisation of these cells will provide new insights into human GI biology, with the potential for developing novel therapies to address the fundamental causes of GI dysmotility. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells: From Structure to Function)
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15 pages, 3029 KiB  
Review
The Telocytes: Ten Years after Their Introduction in the Scientific Literature. An Update on Their Morphology, Distribution, and Potential Roles in the Gut
by Maria Giuliana Vannucchi
Int. J. Mol. Sci. 2020, 21(12), 4478; https://doi.org/10.3390/ijms21124478 - 24 Jun 2020
Cited by 43 | Viewed by 4827
Abstract
Ten years ago, the term ‘telocyte’ was introduced in the scientific literature to describe a ‘new’ cell type described in the connective tissue of several organs by Popescu and Faussone-Pellegrini (2010). Since then, 368 papers containing the term ‘telocyte’ have been [...] Read more.
Ten years ago, the term ‘telocyte’ was introduced in the scientific literature to describe a ‘new’ cell type described in the connective tissue of several organs by Popescu and Faussone-Pellegrini (2010). Since then, 368 papers containing the term ‘telocyte’ have been published, 261 of them in the last five years. These numbers underscore the growing interest in this cell type in the scientific community and the general acceptance of the name telocyte to indicate this interstitial cell. Most of these studies, while confirming the importance of transmission electron microscopy to identify the telocytes with certainty, highlight the variability of their immune phenotypes. This variability was interpreted as due to (i) the ability of the telocytes to adapt to the different sites in which they reside; (ii) the distinct functions they are likely to perform; and (iii) the existence of telocyte subtypes. In the present paper, an overview of the last 10 years of literature on telocytes located in the gut will be attempted, confining the revision to the morphological findings. A distinct chapter will be dedicated to the recently hypothesized role of the telocytes the intestinal mucosa. Through this review, it will be shown that telocytes, despite their variability, are a unique interstitial cell. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells: From Structure to Function)
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21 pages, 7828 KiB  
Review
Telocytes in the Normal and Pathological Peripheral Nervous System
by Lucio Díaz-Flores, Ricardo Gutiérrez, Mª Pino García, Sara Gayoso, Emma Gutiérrez, Lucio Díaz-Flores, Jr. and José Luis Carrasco
Int. J. Mol. Sci. 2020, 21(12), 4320; https://doi.org/10.3390/ijms21124320 - 17 Jun 2020
Cited by 19 | Viewed by 3530
Abstract
We studied telocytes/CD34+ stromal cells in the normal and pathological peripheral nervous system (PNS), for which we reviewed the literature and contributed our observations under light and electron microscopy in this field. We consider the following aspects: (A) general characteristics of telocytes and [...] Read more.
We studied telocytes/CD34+ stromal cells in the normal and pathological peripheral nervous system (PNS), for which we reviewed the literature and contributed our observations under light and electron microscopy in this field. We consider the following aspects: (A) general characteristics of telocytes and the terminology used for these cells (e.g., endoneurial stromal cells) in PNS; (B) the presence, characteristics and arrangement of telocytes in the normal PNS, including (i) nerve epi-perineurium and endoneurium (e.g., telopodes extending into the endoneurial space); (ii) sensory nerve endings (e.g., Meissner and Pacinian corpuscles, and neuromuscular spindles); (iii) ganglia; and (iv) the intestinal autonomic nervous system; (C) the telocytes in the pathologic PNS, encompassing (i) hyperplastic neurogenic processes (neurogenic hyperplasia of the appendix and gallbladder), highly demonstrative of telocyte characteristics and relations, (ii) PNS tumours, such as neurofibroma, schwannoma, granular cell tumour and nerve sheath myxoma, and interstitial cell of Cajal-related gastrointestinal stromal tumour (GIST), (iii) tumour-invaded nerves and (iv) traumatic, metabolic, degenerative or genetic neuropathies, in which there are fewer studies on telocytes, e.g., neuroinflammation and nerves in undescended testicles (cryptorchidism), Klinefelter syndrome, crush injury, mucopolysaccharidosis II (Hunter’s syndrome) and Charcot–Marie–Tooth disease. Full article
(This article belongs to the Special Issue Telocytes and Other Interstitial Cells: From Structure to Function)
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