Type Of Interstitial Cells Research Articles

The History of Telocyte Discovery and Understanding.

Telocytes (TCs) are identified as a peculiar cell type of interstitial cells in various organs. The typical features of TCs from the other cells are the extending cellular process as telopodes with alternation of podomeres and podoms. Before the year of 2010, TCs were considered as interstitial Cajal-like cells because of the similar morphology and immunohistochemical features with interstitial cells of Cajal which were found more than 100 years ago and considered to be pacemakers for gut motility. Subsequently, it demonstrated that TCs were not Cajal-like cells, and thus the new name "telocyte" was proposed in 2010. With the help of different techniques, e.g., transmission electron microscopy, immunohistochemistry, or omics science, TCs have been detected in various tissues and organs from different species. The pathological role of TCs in different diseases was also studied. According to observation in situ or in vitro, TCs played a vital role in mechanical support, signaling transduction, tissue renewal or repair, immune surveillance, and mechanical sensor via establishing homo- or heterogenous junctions with neighboring cells to form 3D network or release extracellular vesicles to form juxtacrine and paracrine. This review will introduce the origin, distribution, morphology, functions, omics science, methods, and interaction of TCs with other cells and provide a better understanding of the new cell type.

A Tale of Two Cells: Telocyte and Stem Cell Unique Relationship.

Telocytes have been identified as a distinctive type of interstitial cells and have been recognized in most tissues and organs. Telocytes are characterized by having extraordinary long cytoplasmic processes, telopodes, that extend to form three-dimensional networks and commonly constitute specialized forms of cell-to-cell junctions with other neighboring cells. Telocytes have been localized in the stem cell niche of different organs such as the heart, lung, skeletal muscle, and skin. Electron microscopy and electron tomography revealed a specialized link between telocytes and stem cells that postulates a potential role for telocytes during tissue regeneration and repair. In this review, the distribution of telocytes in different stem cell niches will be explored, highlighting the intimate relationship between the two types of cells and their possible functional relationship.

Ultrastructural identification of telocytes in the muscularis of chicken ileum.

Telocytes (TCs) are a specialized type of interstitial cells, characterized by a small cell body and long, thin processes, that have recently been identified in various cavitary and non-cavitary organs of humans and laboratory mammals. Chickens present significant economical and scientific notability; however, ultrastructural identification of TCs remains unclear in birds. The aim of the present study was to describe electron microscopic evidence for the presence of TCs in the chicken gut. The ileum of healthy adult broiler chickens (n=10) was studied by transmission electron microscopy. TCs are characterized by several, long (tens to hundreds of µm) prolongations called telopodes (Tps). Tps, which are below the resolving power of light microscopy, display podomeres (thin segments of ≤0.2 µm) and podoms (dilations accommodating caveolae, mitochondria and endoplasmic reticulum). TCs were observed in every field, but were predominantly located in the myenteric plexus and the lamina propria. Tps frequently establish close spatial relationships with immune cells, blood vessels and nerve endings. On the basis of their distribution and morphology, it was hypothesized that the different locations of TCs may be associated with different roles.

Global comparison of chromosome X genes of pulmonary telocytes with mesenchymal stem cells, fibroblasts, alveolar type II cells, airway epithelial cells, and lymphocytes

BackgroundTelocytes (TCs) are suggested as a new type of interstitial cells with specific telopodes. Our previous study evidenced that TCs differed from fibroblasts and stem cells at the aspect of gene expression profiles. The present study aims to search the characters and patterns of chromosome X genes of TC-specific or TC-dominated gene profiles and fingerprints, investigate the network of principle genes, and explore potential functional association.MethodsWe compared gene expression profiles in chromosome X of pulmonary TCs with mesenchymal stem cells (MSC), fibroblasts (Fb), alveolar type II cells (ATII), airway basal cells (ABC), proximal airway cells (PAC), CD8+ T cells come from bronchial lymph nodes (T-BL), or CD8+ T cells from lungs (T-L) by global analyses, and selected the genes which were consistently up or down regulated (>1 fold) in TCs compared to other cells as TC-specific genes. The functional and characteristic networks were identified and compared by bioinformatics tools.ResultsWe selected 31 chromosome X genes as the TC-specific or dominated genes, among which 8 up-regulated (Flna, Msn, Cfp, Col4a5, Mum1l1, Rnf128, Syn1, and Srpx2) and 23 down-regulated (Abcb7, Atf1, Ddx26b, Drp2, Fam122b, Gyk, Irak1, Lamp2, Mecp2, Ndufb11, Ogt, Pdha1, Pola1, Rab9, Rbmx2, Rhox9, Thoc2, Vbp1, Dkc1, Nkrf, Piga, Tmlhe and Tsr2), as compared with other cells.ConclusionsOur data suggested that gene expressions of chromosome X in TCs are different with those in other cells in the lung tissue. According to the selected TC-specific genes, we infer that pulmonary TCs function as modulators which may enhance cellular growth and migration, resist senescence, protect cells from external stress, regulate immune responses, participate in tissue remodeling and repair, regulate neural function, and promote vessel formation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0669-8) contains supplementary material, which is available to authorized users.

Skin telocytes versus fibroblasts: two distinct dermal cell populations.

It is already accepted that telocytes (TCs) represent a new type of interstitial cells in human dermis. In normal skin, TCs have particular spatial relations with different dermal structures such as blood vessels, hair follicles, arrector pili muscles or segments of sebaceous and/or eccrine sweat glands. The distribution and the density of TCs is affected in various skin pathological conditions. Previous studies mentioned the particular (ultra)structure of TCs and also their immunophenotype, miR imprint or proteome, genome or secretome features. As fibroblast is the most common intersitital cell (also in human dermis), a dedicated comparison between human skin TCs and fibroblasts (Fbs) was required to be performed. In this study, using different techniques, we document several points of difference between human dermis TCs and Fbs. By transmission electron microscopy (TEM) and scanning electron microscopy (SEM), we demonstrated TCs with their hallmark cellular prolongations – telopodes. Thus, we showed their ultrastructural distinctiveness from Fbs. By RayBio Human Cytokine Antibody Array V analyses performed on the supernatant from separately cultured TCs and Fbs, we detected the cytokine profile of both cell types, individually. Two of 79 detected cytokines – epithelial-derived neutrophil-activating peptide 78 and granulocyte chemotactic protein-2 – were 1.5 times higher in the supernatant of TCs (comparing with Fbs). On the other hand, 37 cytokines were at least 1.5 higher in Fbs supernatant (comparing with TCs), and among them six cytokines – interleukin 5, monocyte chemotactic protein-3 (MCP-3), MCP-4, macrophage inflammatory protein-3, angiogenin, thrombopoietin – being 9.5 times higher (results also confirmed by ELISA testing). In summary, using different techniques, we showed that human dermal TCs and Fbs are different in terms of ultrastructure and cytokine profile.

Telocytes in the Spleen.

Telocytes, a novel type of interstitial cells with very long and thin prolongations, have been identified in many organs in mammals. At present, the ultrastructural, immunocytochemical and electrophysiological properties of telocytes in multiple organs have been understood. However, telocytes in spleen, especially their roles in spleen have not been reported. The aim of this study was to investigate the ultrastructure, distribution and immunophenotypes of splenic telocytes. Rat spleen was harvested for the ultrastructure analysis by transmission electron microscopy (TEM). The primary culture of telocytes was performed after combined enzymatic digestion. The characteristic morphology was analyzed by a scanning electron microscopy (SEM). It was shown that telocytes displayed a piriform/spindle/triangular shape with long and slender telopods and extremely long prolongation contracting with surrounding cells in the spleen. Their dynamic profiles of cytoplasmic separation were recorded by the Live Cell Imaging System. The length of telopods was mostly distributing in 20–30 μm, in accordance with normal distribution. Most telocytes had three or two telopods (28.71% and 22.58% respectively). Immunostaining indicated that these cells were positive for vimentin, CD34, nanog and sca-1, but negative for c-kit. These data prove the existence of telocytes in the spleen, which may serve as the experimental base for exploring their roles in the spleen.

Electron microscopy of human fascia lata: focus on telocytes.

From the histological point of view, fascia lata is a dense connective tissue. Although extracellular matrix is certainly the most predominant fascia’s feature, there are also several cell populations encountered within this structure. The aim of this study was to describe the existence and characteristics of fascia lata cell populations viewed through a transmission electron microscope. Special emphasis was placed on telocytes as a particular interstitial cell type, recently discovered in a wide variety of tissues and organs such as the heart, skeletal muscles, skin, gastrointestinal tract, uterus and urinary system. The conducted study confirmed the existence of a telocyte population in fascia lata samples. Those cells fulfil main morphological criteria of telocytes, namely, the presence of very long, thin cell processes (telopodes) extending from a relatively small cell body. Aside from telocytes, we have found fibroblasts, mast cells and cells with features of myofibroblastic differentiation. This is the first time it has been shown that telocytes exist in human fascia. Currently, the exact role of those cells within the fascia is unknown and definitely deserves further attention. One can speculate that fascia lata telocytes likewise telocytes in other organs may be involved in regeneration, homeostasis and intracellular signalling.

The failing human heart is characterized by decreased numbers of telocytes as result of apoptosis and altered extracellular matrix composition.

Telocytes (TCs) are a novel type of interstitial cells only recently described. This study aimed at characterizing and quantifying TCs and telopodes (Tps) in normal and diseased hearts. We have been suggested that TCs are influenced by the extracellular matrix (ECM) composition. We used transmission electron microscopy and c-kit immunolabelling to identify and quantify TCs in explanted human hearts with heart failure (HF) because of dilated, ischemic or inflammatory cardiomyopathy. LV myectomy samples from patients with aortic stenosis with preserved ejection fraction and samples from donor hearts which could not be used for transplantation served as controls. Quantitative immunoconfocal analysis revealed that 1 mm2 of the normal myocardium contains 14.9 ± 3.4 TCs and 41.6 ± 5.9 Tps. As compared with the control group, the number of TCs and Tps in HF decreased more than twofold. There were no differences between HF and control in the number of Ki67-positive TCs. In contrast, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive TCs increased threefold in diseased hearts as compared to control. Significant inverse correlations were found between the amount of mature fibrillar collagen type I and the number of TCs (r = −0.84; P < 0.01) and Tps (r = −0.85; P < 0.01). The levels of degraded collagens showed a significant positive relationship with the TCs numbers. It is concluded that in HF the number of TCs are decreased because of higher rates of TCs apoptosis. Moreover, our results indicate that a close relationship exists between TCs and the ECM protein composition such that the number of TCs and Tps correlates negatively with the amount of mature fibrillar collagens and correlates positively with degraded collagens.

Covering the Cover

Covering the Cover

Cardiac telocytes are double positive for CD34/PDGFR‐α

Telocytes (TCs) are a distinct type of interstitial cells, which are featured with a small cellular body and long and thin elongations called telopodes (Tps). TCs have been widely identified in lots of tissues and organs including heart. Double staining for CD34/PDGFR-β (Platelet-derived growth factor receptor β) or CD34/Vimentin is considered to be critical for TC phenotyping. It has recently been proposed that CD34/PDGFR-α (Platelet-derived growth factor receptor α) is actually a specific marker for TCs including cardiac TCs although the direct evidence is still lacking. Here, we showed that cardiac TCs were double positive for CD34/PDGFR-α in primary culture. CD34/PDGFR-α positive cells (putative cardiac TCs) also existed in mice ventricle and human cardiac valves including mitral valve, tricuspid valve and aortic valve. Over 87% of cells in a TC-enriched culture of rat cardiac interstitial cells were positive for PDGFR-α, while CD34/PDGFR-α double positive cells accounted for 30.25% of the whole cell population. We show that cardiac TCs are double positive for CD34/PDGFR-α. Better understanding of the immunocytochemical phenotypes of cardiac TCs might help using cardiac TCs as a novel source in cardiac repair.

Telocytes in regenerative medicine.

Telocytes (TCs) are a distinct type of interstitial cells characterized by a small cell body and extremely long and thin telopodes (Tps). The presence of TCs has been documented in many tissues and organs (go to http://www.telocytes.com). Functionally, TCs form a three-dimensional (3D) interstitial network by homocellular and heterocellular communication and are involved in the maintenance of tissue homeostasis. As important interstitial cells to guide or nurse putative stem and progenitor cells in stem cell niches in a spectrum of tissues and organs, TCs contribute to tissue repair and regeneration. This review focuses on the latest progresses regarding TCs in the repair and regeneration of different tissues and organs, including heart, lung, skeletal muscle, skin, meninges and choroid plexus, eye, liver, uterus and urinary system. By targeting TCs alone or in tandem with stem cells, we might promote regeneration and prevent the evolution to irreversible tissue damage. Exploring pharmacological or non-pharmacological methods to enhance the growth of TCs would be a novel therapeutic strategy besides exogenous transplantation for many diseased disorders.

Cardiac telocytes and fibroblasts in primary culture: different morphologies and immunophenotypes.

Telocytes (TCs) are a peculiar type of interstitial cells with very long prolongations termed telopodes. TCs have previously been identified in different anatomic structures of the heart, and have also been isolated and cultured from heart tissues in vitro. TCs and fibroblasts, both located in the interstitial spaces of the heart, have different morphologies and functionality. However, other than microscopic observation, a reliable means to make differential diagnosis of cardiac TCs from fibroblasts remains unclear. In the present study, we isolated and cultured cardiac TCs and fibroblasts from heart tissues, and observed their different morphological features and immunophenotypes in primary culture. Morphologically, TCs had extremely long and thin telopodes with moniliform aspect, stretched away from cell bodies, while cell processes of fibroblasts were short, thick and cone shaped. Furthermore, cardiac TCs were positive for CD34/c-kit, CD34/vimentin, and CD34/PDGFR-β, while fibroblasts were only vimentin and PDGFR-β positive. In addition, TCs were also different from pericytes as TCs were CD34 positive and α-SMA weak positive while pericytes were CD34 negative but α-SMA positive. Besides that, we also showed cardiac TCs were homogenously positive for mesenchymal marker CD29 but negative for hematopoietic marker CD45, indicating that TCs could be a source of cardiac mesenchymal cells. The differences in morphological features and immunophenotypes between TCs and fibroblasts will provide more compelling evidence to differentiate cardiac TCs from fibroblasts.

Telocytes in human liver fibrosis.

Liver fibrosis is a wound-healing response which engages a variety of cell types to encapsulate injury. Telocyte (TC), a novel type of interstitial cell, has been identified in a variety of tissues and organs including liver. TCs have been reported to be reduced in fibrotic areas after myocardial infarction, human interstitial wall's fibrotic remodelling caused either by ulcerative colitis or Crohn's disease, and skin of systemic sclerosis. However, the role of TCs in human liver fibrosis remains unclear. Liver samples from human liver biopsy were collected. All samples were stained with Masson's trichrome to determine fibrosis. TCs were identified by several immunofluorescence stainings including double labelling for CD34 and c-kit/CD117, or vimentin, or PDGF Receptor-α, or β. We found that hepatic TCs were significantly decreased by 27%–60% in human liver fibrosis, suggesting that loss of TCs might lead to the altered organization of extracellular matrix and loss the control of fibroblast/myofibroblast activity and favour the genesis of fibrosis. Adding TCs might help to develop effective and targeted antifibrotic therapies for human liver fibrosis.

Morphological evidence of telocytes in mice aorta.

Background:Telocytes (TCs) are a novel type of interstitial cells, which have been recently described in a large variety of cavitary and noncavitary organs. TCs have small cell bodies, and remarkably thin, long, and moniliform prolongations called telopodes (Tps). Until now, TCs have been found in various loose connective tissues surrounding the arterioles, venules, and capillaries, but as a histological cellular component, whether TCs exist in large arteries remains unexplored.Methods:TCs were identified by transmission electron microscope in the aortic arch of male C57BL/6 mice.Results:TCs in aortic arch had small cell bodies (length: 6.06–13.02 μm; width: 1.05–4.25 μm) with characteristics of specific long (7.74–39.05 μm), thin, and moniliform Tps; TCs distributed in the whole connective tissue layer of tunica adventitia: TCs in the innermost layer of tunica adventitia, located at the juncture between media and adventitia, with their long axes oriented parallel to the outer elastic membrane; and TCs in outer layers of tunica adventitia, were embedded among transverse and longitudinal oriented collagen fibers, forming a highly complex three-dimensional meshwork. Moreover, desmosomes were observed, serving as pathways connecting neighboring Tps. In addition, vesicles shed from the surface of TCs into the extracellular matrix, participating in some biological processes.Conclusions:TCs in aorta arch are a newly recognized complement distinct from other interstitial cells in large arteries, such as fibroblasts. And further biologically functional correlations need to be elucidated.

Telocytes in human coronary arteries – scanning electron microscope study

Introduction: A telocyte is a novel type of interstitial cell in the stromal connective tissue of many animals and human organs. Morphologically, telocytes are composed of small cell bodies with telopodes – very long prolongations of uneven calibre. The existence of telopodes and the 3D network indicates that telocytes may function in intercellular communication and regulation. The presence of telocytes has been identified in human heart valves, atria, ventricles, but not yet in human coronary arteries. The pro-angiogenesis behaviour of telocytes and their close spatial relationships with newly formed blood vessels was outlined within the border zone of myocardial infarction. Objectives: To show visual evidence of the presence of telocytes within human coronary arteries. Materials and methods: Human coronary arteries were collected during routine forensic medical autopsies from people who did not have cardiovascular pathologies. The endothelial surface of human coronary arteries was examined and the images were captured using a scanning electron microscope. The study was approved by the Bioethical Committee of the Jagiellonian University Medical College. Results: Telocytes were present on the endothelial surface of human coronary arteries and had one to six long telopodes emerging from the small cell body (varying in shape depending on the number of telopodes). Telocytes seem to be adherent to the endothelial surface. They appear either singular or in groups and their density differs by region. Contacts between telopodes of two distinct adjacent telocytes were observed. Conclusions: We provide visual evidence for the presence of telocytes on the endothelial surface in human coronary arteries. It remains to be determined how telocytes support the ability of arteries to re-establish normal structure and function following injury and its impact on the regeneration of infarcted myocardium. Acknowledgements: Dr WieslawaKlimek-Piotrowska MD, PhD, for supervising this project.

Global analyses of Chromosome 17 and 18 genes of lung telocytes compared with mesenchymal stem cells, fibroblasts, alveolar type II cells, airway epithelial cells, and lymphocytes.

BackgroundTelocytes (TCs) is an interstitial cell with extremely long and thin telopodes (Tps) with thin segments (podomers) and dilations (podoms) to interact with neighboring cells. TCs have been found in different organs, while there is still a lack of TCs-specific biomarkers to distinguish TCs from the other cells.ResultsWe compared gene expression profiles of murine pulmonary TCs on days 5 (TC5) and days 10 (TC10) with mesenchymal stem cells (MSCs), fibroblasts (Fbs), alveolar type II cells (ATII), airway basal cells (ABCs), proximal airway cells (PACs), CD8+ T cells from bronchial lymph nodes (T-BL), and CD8+ T cells from lungs (T-LL). The chromosome 17 and 18 genes were extracted for further analysis. The TCs-specific genes and functional networks were identified and analyzed by bioinformatics tools. 16 and 10 of TCs-specific genes were up-regulated and 68 and 22 were down-regulated in chromosome 17 and 18, as compared with other cells respectively. Of them, Mapk14 and Trem2 were up-regulated to indicate the biological function of TCs in immune regulation, and up-regulated MCFD2 and down-regulated E4F1 and PDCD2 had an association with tissue homeostasis for TCs. Over-expressed Dpysl3 may promote TCs self-proliferation and cell-cell network forming.ConclusionsThe differential gene expression in chromosomes 17 and 18 clearly revealed that TCs were the distinctive type of interstitial cells. Our data also indicates that TCs may play a dual role in immune surveillance and immune homoeostasis to keep from immune disorder in acute and chronic pulmonary diseases. TCs also participated in proliferation, differentiation and regeneration.ReviewersThis article was reviewed by Qing Kay Li and Dragos Cretoiu.Electronic supplementary materialThe online version of this article (doi:10.1186/s13062-015-0042-0) contains supplementary material, which is available to authorized users.

Telocytes revisited.

Telocytes (TCs) are a novel interstitial (stromal) cell type described in many tissues and organs (www.telocytes.com). A TC is characterized by a small cell body (9-15 μm) and a variable number (one to five) of extremely long and thin telopodes (Tps), with alternating regions of podomers (∼80 nm) and podoms (250-300 nm). Tps are interconnected by homo- and heterocellular junctions and form three-dimensional networks. Moreover, Tps release three types of extracellular vesicles: exosomes, ectosomes, and multivesicular cargos, which are involved in paracrine signaling. Different techniques have been used to characterize TCs, from classical methods (light microscopy, electron microscopy) to modern 'omics'. It is considered that electron microscopy is essential for their identification, and CD34/PDGFRα double immunohistochemistry can orientate the diagnosis. Functional evidence is accumulating that TCs may be intimately involved in the maintenance of tissue homeostasis and renewal by short- and long-distance intercellular communication. This review focuses on the most recent findings regarding TC features and locations and the principal hypotheses about their functions in normal and diseased organs. TC involvement in regenerative medicine is also considered.

Telocytes in liver regeneration: possible roles.

Telocytes (TCs) are a novel type of interstitial cells which are potentially involved in tissue regeneration and repair (http://www.telocytes.com). Previously, we documented the presence of TCs in liver. However, the possible roles of TCs in liver regeneration remain unknown. In this study, a murine model of partial hepatectomy (PH) was used to induce liver regeneration. The number of TCs detected by double labelling immunofluorescence methods (CD34/PDGFR-α, CD34/PDGFR-ß and CD34/Vimentin) was significantly increased when a high level of hepatic cell proliferation rate (almost doubled) as shown by 5-ethynyl-2′-deoxyuridine (EdU) immunostaining and Western Blot of Proliferating cell nuclear antigen (PCNA) was found at 48 and 72 hrs post-PH. Meanwhile, the number of CK-19 positive-hepatic stem cells peaked at 72 hrs post-PH, co-ordinating with the same time-point, when the number of TCs was most significantly increased. Taken together, the results indicate a close relationship between TCs and the cells essentially involved in liver regeneration: hepatocytes and stem cells. It remains to be determined how TCs affect hepatocytes proliferation and/or hepatic stem cell differentiation in liver regeneration. Besides intercellular junctions, we may speculate a paracrine effect via ectovesicles.

Telocytes in mice bone marrow: electron microscope evidence.

Telocytes (TCs) are a novel type of interstitial cell of whom presence has been recently documented in many tissues and organs. However, whether TCs exists in bone marrow is still not reported. This study aims to find out TCs in mice bone marrow by using scanning electron microscope (SEM) and transmission electron microscope (TEM). SEM images showed that in mice bone marrow most of TCs have small spherical cell body (usually 4–6 μm diameter) with thin long telopodes (Tps; usually one to three). The longest Tp observed was about 70 μm, with an uneven calibre. Direct intercellular contacts exist between TCs. TEM shows mitochondria within dilations of Tps. Also, by TEM, we show the close spatial relations of Tps with blood vessels. In conclusion, this study provides ultrastructural evidence regarding the existence of TCs in mice bone marrow, in situ.

Differences in the expression of chromosome 1 genes between lung telocytes and other cells: mesenchymal stem cells, fibroblasts, alveolar type II cells, airway epithelial cells and lymphocytes.

Telocytes (TCs) are a unique type of interstitial cells with specific, extremely long prolongations named telopodes (Tps). Our previous study showed that TCs are distinct from fibroblasts (Fbs) and mesenchymal stem cells (MSCs) as concerns gene expression and proteomics. The present study explores patterns of mouse TC-specific gene profiles on chromosome 1. We investigated the network of main genes and the potential functional correlations. We compared gene expression profiles of mouse pulmonary TCs, MSCs, Fbs, alveolar type II cells (ATII), airway basal cells (ABCs), proximal airway cells (PACs), CD8+ T cells from bronchial lymph nodes (T-BL) and CD8+ T cells from lungs (T-LL). The functional and feature networks were identified and compared by bioinformatics tools. Our data showed that on TC chromosome 1, there are about 25% up-regulated and 70% down-regulated genes (more than onefold) as compared with the other cells respectively. Capn2, Fhl2 and Qsox1 were over-expressed in TCs compared to the other cells, indicating that biological functions of TCs are mainly associated with morphogenesis and local tissue homoeostasis. TCs seem to have important roles in the prevention of tissue inflammation and fibrogenesis development in lung inflammatory diseases and as modulators of immune cell response. In conclusion, TCs are distinct from the other cell types.