Type Of Interstitial Cells Research Articles

Morphologies and potential roles of telocytes in nervous tissue

AbstractStructurally similar cells have been found and termed telocytes (TCs) since the first characterisation of interstitial Cajal‐like cells in 1911. TCs are a novel and peculiar interstitial cell type with a small cellular body, markedly long cell processes named telopodes and a wide distribution in numerous tissues throughout the body. Besides specific morphological characteristics and immunohistochemical profiles, TCs build three‐dimensional mixed networks through homocellular (connection to each other) and/or heterocellular contacts (connection with other cell types), interaction with extracellular matrix and their vicinity to nerve endings, and thus might play, as part of an integrated system, roles in maintaining organ/tissue function. In this mini‐review, we summarise physical properties, general characteristics and distribution of TCs in diverse organs and tissues, focusing on their potential functions in nervous tissue and current challenges in investigating TCs as a distinct cell type.

Single-cell profiling reveals various types of interstitial cells in the bladder.

Clarifying the locations, molecular markers, functions and roles of bladder interstitial cells is crucial for comprehending the pathophysiology of the bladder. This research utilized human, rat and mouse bladder single-cell sequencing, bioinformatics analysis and experimental validation. The main cell types found in human, rat and mouse bladder tissues include epithelial cells, smooth muscle cells, endothelial cells, fibroblasts, myofibroblasts, neurons and various immune cells. Our study identified two significant types of interstitial cells (PTN+ IGFBP6+ PI16 (CD364)+ CD34+ ) and myofibroblasts (STC1+ PLAT+ TNC+ ). These two types of interstitial cells are mainly located in the subepithelial lamina propria, between muscles and between muscle bundles. In the CYP (cyclophosphamide)-induced bladder injury mouse model, the interaction types and signals (MK, MIF, GDF and CXCL) of fibroblasts and myofibroblasts significantly increased compared with the normal group. However, in the aging mouse model, the signals CD34, LAMININ, GALECTIN, MK, SELPLG, ncWNT, HSPG, ICAM and ITGAL-ITGB2 of fibroblasts and myofibroblasts disappeared, but the signals PTN and SEMA3 significantly increased. Our findings identified two crucial types of interstitial cells in bladder tissue, fibroblasts and myofibroblasts, which play a significant role in normal bladder physiology, CYP-induced bladder injury and aging bladder development.

Distributions of Platelet-Derived Growth Factor Receptor-α Positive Cells and Interstitial Cells of Cajal in the Colon of Rats with Diabetes Mellitus Type 2.

Background and Objectives: Diabetic gastroenteropathy (DG) is a common complication of diabetes mellitus type 2. Interstitial cells are non-neural cells of mesenchymal origin inserted between nerve elements and smooth muscle cells, necessary for normal function and peristaltic contractions in the gastrointestinal (GI) tract. There are at least two types of interstitial cells within the GI muscle layer-interstitial cells of Cajal (ICC) and interstitial platelet-derived growth factor receptor α-positive cells (IPC). The mechanism of diabetic gastroenteropathy is unclear, and interstitial cells disorders caused by metabolic changes in diabetes mellitus (DM) could explain the symptoms of DG (slow intestinal transit, constipation, fecal incontinence). The aim of this study was to identify PDGFRα and c-kit immunoreactive cells in the colon of rats with streptozotocin-nicotinamide-induced diabetes mellitus type 2, as well as to determine their distribution in relation to smooth muscle cells and enteric nerve structures. Materials and Methods: Male Wistar rats were used, and diabetes type 2 was induced by an intraperitoneal injection of streptozotocin, immediately after intraperitoneal application of nicotinamide. The colon specimens were exposed to PDGFRα and anti-c-kit antibodies to investigate interstitial cells; enteric neurons and smooth muscle cells were immunohistochemically labeled with NF-M and desmin antibodies. Results: Significant loss of the intramuscular ICC, myenteric ICC, and loss of their connection in intramuscular linear arrays and around the ganglion of the myenteric plexus were observed with no changes in nerve fiber distribution in the colon of rats with diabetes mellitus type 2. IPC were rarely present within the colon muscle layer with densely distributed PDGFRα+ cells in the colon mucosa and submucosa of both experimental groups. In summary, a decrease in intramuscular ICC, discontinuities and breakdown of contacts between myenteric ICC without changes in IPC and nerve fibers distribution were observed in the colon of streptozotocin/nicotinamide-induced diabetes type 2 rats.

Autonomic innervation, a peripheral glial cell web, and a novel S100B expressing interstitial cell type impart structural and functional complexity to the sinoatrial node.

The sinoatrial node (SAN) of the heart produces rhythmic action potentials, generated via calcium signaling within and among pacemaker cells. Our previous work has described the SAN as composed of a HCN4+-pacemaker cell meshwork, which merges with a network of connexin 43+/F-actin+ cells. It is also known that sympathetic and parasympathetic innervation create an autonomic plexus in the SAN that modulates heart rate and rhythm. However, the anatomical details of the interaction of this plexus with the pacemaker cell meshwork have yet to be described. The cytoarchitecture of SAN whole-mount preparations was examined by three-dimensional confocal laser scanning microscopy of triple immunolabeled with combinations of antibodies for HCN4, S100 calcium-binding protein B (S100B), glial fibrillary acidic protein (GFAP), choline acetyltransferase, or vesicular acetylcholine transporter, and tyrosine hydroxylase, and transmission electron microscopy. The SAN exhibited heterogeneous autonomic innervation, which was accompanied by a web of peripheral glial cells and a novel S100B+/GFAP- interstitial cell population, with a unique morphology and a distinct distribution pattern, creating complex interactions with other cell types in the node, particularly with HCN4-expressing cells. Transmission electron microscopy identified a similar population of interstitial cells as telocytes, which appeared to secrete vesicles toward pacemaker cells. Application of S100B to SAN preparations desynchronized Ca2þ signaling in HCN4-expressing cells and increased variability in SAN impulse rate and rhythm. The autonomic plexus, peripheral glial cell web, and a novel S100Bþ/GFAP- interstitial cell type embedded within the HCN4þ cell meshwork increase the structural and functional complexity of the SAN and provide a new regulatory pathway of rhythmogenesis.

Gene expression studies of WT1 mutant Wilms tumor cell lines in the frame work of published kidney development data reveals their early kidney stem cell origin.

In order to get a better insight into the timing of WT1 mutant Wilms tumor development, we compared the gene expression profiles of nine established WT1 mutant Wilms tumor cell lines with published data from different kidney cell types during development. Publications describing genes expressed in nephrogenic precursor cells, ureteric bud cells, more mature nephrogenic epithelial cells and interstitial cell types were used. These studies uncovered that the WT1 mutant Wilms tumor cells lines express genes from the earliest nephrogenic progenitor cells, as well as from more differentiated nephron cells with the highest expression from the stromal/interstitial compartment. The expression of genes from all cell compartments points to an early developmental origin of the tumor in a common stem cell. Although variability of the expression of specific genes was evident between the cell lines the overall expression pattern was very similar. This is likely dependent on their different genetic backgrounds with distinct WT1 mutations and the absence/presence of mutant CTNNB1.

Telocyte-Derived Exosomes Provide an Important Source of Wnts That Inhibits Fibrosis and Supports Regeneration and Repair of Endometrium

Intrauterine adhesions (IUAs) often occurred after common obstetrical and gynecological procedures or infections in women of reproductive age. It was characterized by the formation of endometrial fibrosis and prevention of endometrial regeneration, usually with devastating fertility consequences and poor treatment outcomes so far. Telocytes (TCs), as a novel interstitial cell type, present in female uterus with in vitro therapeutic potential in decidualization-defective gynecologic diseases. This study aims to further investigate the role of TC-derived Wnt ligands carried by exosomes (Exo) in reversal of fibrosis and enhancement of regeneration repair in endometrium. IUA cellular and animal models were established from endometrial stromal cells (ESCs) and mice, followed with treatment of TC-conditioned medium (TCM) or TC-derived Exo. In cellular model, fibrosis markers (collagen type 1 alpha 1 [COL1A1], fibronectin [FN], and α-smooth muscle actin [α-SMA]), angiogenesis (vascular endothelial growth factor [VEGF]), and pathway protein (β-catenin) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting (WB), and immunofluorescence. Results showed that, TCs (either TCM or TC-derived Exo) provide a source of Wnts that inhibit cellular fibrosis, as evidenced by significantly elevated VEGF and β-catenin with decreased fibrotic markers, whereas TCs lost salvage on fibrosis after being blocked with Wnt/β-catenin inhibitors (XAV939 or ETC-159). Further in mouse model, regeneration repair (endometrial thickness, number of glands, and fibrosis area ratio), fibrosis markers (fibronectin [FN]), mesenchymal–epithelial transition (MET) (E-cadherin, N-cadherin), and angiogenesis (VEGF, microvessel density [MVD]) were studied by hematoxylin–eosin (HE), Masson staining, and immunohistochemistry. Results demonstrated that TC-Exo treatment effectively promotes regeneration repair of endometrium by relieving fibrosis, enhancing MET, and angiogenesis. These results confirmed new evidence for therapeutic perspective of TC-derived Exo in IUAs.

Distribution of interstitial cells of Cajal and nerve fibers in rat stomach in streptozotocin-nicotinamide-induced diabetes mellitus

Diabetic peristalsis disorders are common complications in diabetes mellitus type 2. Disturbance of interstitial cells of Cajal (ICC) caused by metabolic changes in diabetes could explain the symptoms of diabetic gastroenteropathy. Although heterogenous interstitial cell types represent only 5% of the cell population of the muscle layer in the gastrointestinal tract (GIT), they are important for conducting electrical signals and regulating muscle excitability. The aim of this study was to investigate the alterations of the myenteric and intramuscular ICCs in the gaster of rats with diabetes mellitus type 2 (DMT2), as well as determine their distribution in relation to smooth muscle cells and enteric nerve structures. Male Wistar rats were used and DT2 was induced by streptozotocin-nicotinamide (STZ-NA) application. The stomach specimens were exposed to type III transmembrane tyrosine kinase (c-KIT), neurofilament (NF-M) protein and desmin antibodies to investigate the ICC, enteric neurons and smooth muscle cells. Morphological changes of the cells were quantified by the numerical areal density of intramuscular ICC, the ICC score of myenteric ICC and the volume density of nerve fibers. In conclusion, a statistically significant decrease in the number of intramuscular ICC and myenteric ICC without nerve fiber loss were observed in all stomach regions in rats with STZ-NA-induced DMT2.

Distribution and Ultrastructural Features of Telocytes in the Pars Distalis of the Rat Pituitary Gland.

Telocytes (TCs), a novel type of interstitial cells, are characterized by their smaller cellular body and extremely long, thin processes which are called telopodes (Tps). They have been described in multiple organs from diverse animals. Currently, the existence of TCs in rat pars distalis (PD) has remained unexplored. This investigation was undertaken to visualize the distribution and structural features of TCs in the PD using immunofluorescence (IF) and further validated by transmission electron microscopy (TEM). HE staining revealed the presence of interstitial cells in the peri-sinusoidal vessels spaces of the PD. Using IF, CD34/vimentin double-positive interstitial cells were identified as TCs in accordance with identification standards. TEM further verified the presence of TCs based on their unique ultrastructural features. TCs exhibited communication structures including cell connections and extracellular vesicles (EVs). Interestingly, TCs were in close proximity to the nerves. Most importantly, Tps extended toward the nerves, blood vessels, and glandular cells. TCs could be the structural foundation of a third regulatory system in rat PD according to the tight connections of TCs with sinusoid vessels, glandular cells, EVs and most crucially the nerves. Taken together, these morphological and structural findings demonstrate that TCs are vital components of the rat PD.

Evaluation of the Plasticity of Novel Regulatory Cells-Telocytes-in the Gonad of the Male Chinese Soft-Shelled Turtle (Pelodiscus sinensis) Associated with Seasonal Reproductive Activity.

Telocyte (TC)—a new type of interstitial cell with long telopodes, can form cellular junctions with various tissues or cells to participate in the regulation of multitudes of physiological activities and diseases. This study aimed to characterize the morphology, molecular features, and potential functions of hormone regulation in Chinese soft-shelled turtle (Pelodiscus sinensis) testis TCs at different reproductive stages by histological evaluation, immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy. During hibernation, TCs were widely distributed in the interstitial tissue. In contrast, during reproductive activity, TCs were noted to be in close proximity with peritubular myoid cells surrounding the seminiferous tubule. Moreover, formed cell–cell junctions were observed between TCs and PTMs. The results of IHC and IF showed that the immunophenotype of testicular TCs in hibernating Chinese soft-shelled turtles is CD34+Vimentin−, while the reproductive telopodes (Tps) show low expression of vimentin. The androgen receptor is expressed in Tps of TCs of testis during hibernation. Our results showed also that TCs in seasonal breeding animals regulate the activity of neighboring cells by releasing extracellular microvesicles (EXMVs), thus influencing the activity of spermatogenesis and steroidogenesis. Consideration of our novel and interesting results indicate that the whole area warrants further research.

Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging.

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.

Significance and perspectives of telocytes in lung diseases

AbstractTelocytes (TCs) are a type of interstitial cells with essential roles in regenerative medicine. TCs spatially exist in the stem cell niche and are considered a ‘stem cell helper cell’. Mesenchymal stromal cells therapy has been widely used in treating lung diseases, while there is increasing evidence from preclinical studies to show the beneficial effects of TCs to support smooth muscle cells and treat lung diseases, by releasing paracrine factors, exosomes, and microvesicles. There are still limitations and challenges to be overcome for TCs‐based translational medicine and clinical applications, by developing new methods and improving therapeutic strategies. The present review overviews the historical development, morphology and spatialization, biomarker specificity and values, biological functions, therapeutic effects on preclinical lung diseases, as well as potential mechanisms and future perspectives in lung diseases. TCs exert beneficial effects on preclinical asthma and acute lung injury and essential roles in repairing injured lung tissues and angiogenesis, by releasing paracrine factors and exosomes.

How to stay attached-Formation of the ricefish plug and changes of internal reproductive structures in the pelvic brooding ricefish, Oryzias eversi Herder et al.(2012) (Beloniformes: Adrianichthyidae).

Teleost fishes show an enormous diversity of parental care, ranging from no care to viviparity with maternal provisioning of embryos. External brooders carry their developing eggs attached to their bodies. This requires the formation of novel morphological structures to support attachment. The pelvic brooding ricefish Oryzias eversi evolved such a structure, called the "plug."The plug anchors attaching filaments from the fertilized eggs inside the female reproductive system, allowing the female to carry the embryos until hatching. Using histological sections and µ-computed tomography scanning, we show that the plug is formed by several types of interstitial cells, blood capillaries, and collagen fibrils that encapsulate the end of the attaching filaments in the anterior part of the gonoduct. Even 15 days after the loss of the protruding attaching filaments, the plug remains. In addition, the developed plug contains multinucleated giant cells that are derived from fusing macrophages. We thus hypothesize that the ricefish plug, which is vital for egg attachment in O. eversi, evolved due to an inflammatory reaction. We assume that it forms similar to a foreign body granuloma, as a reaction to irritation or injury of the gonoduct epithelium by the attaching filaments. Our study further corroborates that pelvic brooding entails a complex set of adaptations to prolonged egg-carrying in the female reproductive system. During brooding, for instance, ovulation in the ovary is suppressed and the anterior part of the gonoduct is characterized by an intricate, recessed folding.

The Heart's Pacemaker Mimics Brain Cytoarchitecture and Function: Novel Interstitial Cells Expose Complexity of the SAN.

The sinoatrial node (SAN) of the heart produces rhythmic action potentials, generated via calcium signaling within and among pacemaker cells. Our previous work has described the SAN as composed of a hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4)-expressing pacemaker cell meshwork, which merges with a network of connexin 43⁺/F-actin⁺ cells. It is also known that sympathetic and parasympathetic innervation create an autonomic plexus in the SAN that modulates heart rate and rhythm. However, the anatomical details of the interaction of this plexus with the pacemaker cell meshwork have yet to be described. This study sought to describe the 3-dimensional cytoarchitecture of the mouse SAN, including autonomic innervation, peripheral glial cells, and pacemaker cells. The cytoarchitecture of SAN whole-mount preparations was examined by three-dimensional confocal laser-scanning microscopy of triple immunolabeled with combinations of antibodies for HCN4, S100 calcium-binding protein B (S100B), glial fibrillary acidic protein (GFAP), choline acetyltransferase, or vesicular acetylcholine transporter, and tyrosine hydroxylase, and transmission electron microscopy. The SAN exhibited heterogeneous autonomic innervation, which was accompanied by a web of peripheral glial cells and a novel S100B⁺/GFAP^- interstitial cell population, with a unique morphology and a distinct distribution pattern, creating complex interactions with other cell types in the node, particularly with HCN4-expressing cells. Transmission electron microscopy identified a similar population of interstitial cells as telocytes, which appeared to secrete vesicles toward pacemaker cells. Application of S100B to SAN preparations desynchronized Ca²⁺ signaling in HCN4-expressing cells and increased variability in SAN impulse rate and rhythm. The autonomic plexus, peripheral glial cell web, and a novel S100B⁺/GFAP^- interstitial cell type embedded within the HCN4⁺ cell meshwork increase the structural and functional complexity of the SAN and provide a new regulatory pathway of rhythmogenesis.

Too bright for 2 dimensions: recent progress in advanced 3-dimensional microscopy of the kidney

The kidney is a structurally and functionally complex organ responsible for the control of water, ion, and other solute homeostasis. Moreover, the kidneys excrete metabolic waste products and produce hormones, such as renin and erythropoietin. The functional unit of the kidney is the nephron, which is composed by a serial arrangement of a filter unit called the renal corpuscle and several tubular segments that modulate the filtered fluid by reabsorption and secretion. Within each kidney, thousands of nephrons are closely intermingled and surrounded by an intricate network of blood vessels and various interstitial cell types, including fibroblasts and immune cells. This complex tissue architecture is essential for proper kidney function. In fact, kidney disease is often reflected or even caused by a derangement of the histologic structures. Frequently, kidney histology is studied using microscopic analysis of 2-dimensional tissue sections, which, however, misses important 3-dimensional spatial information. Reconstruction of serial sections tries to overcome this limitation, but is technically challenging, time-consuming, and often inherently linked to sectioning artifacts. In recent years, advances in tissue preparation (e.g., optical clearing) and new light- and electron-microscopic methods have provided novel avenues for 3-dimensional kidney imaging. Combined with novel machine-learning algorithms, these approaches offer unprecedented options for large-scale and automated analysis of kidney structure and function. This review provides a brief overview of these emerging imaging technologies and presents key examples of how these approaches are already used to study the normal and the diseased kidney.

A Sedentary and Unhealthy Lifestyle Fuels Chronic Disease Progression by Changing Interstitial Cell Behaviour: A Network Analysis.

Managing chronic diseases, such as heart disease, stroke, diabetes, chronic lung disease and Alzheimer’s disease, account for a large proportion of health care spending, yet they remain in the top causes of premature mortality and are preventable. It is currently accepted that an unhealthy lifestyle fosters a state of chronic low-grade inflammation that is linked to chronic disease progression. Although this is known to be related to inflammatory cytokines, how an unhealthy lifestyle causes cytokine release and how that in turn leads to chronic disease progression are not well known. This article presents a theory that an unhealthy lifestyle fosters chronic disease by changing interstitial cell behavior and is supported by a six-level hierarchical network analysis. The top three networks include the macroenvironment, social and cultural factors, and lifestyle itself. The fourth network includes the immune, autonomic and neuroendocrine systems and how they interact with lifestyle factors and with each other. The fifth network identifies the effects these systems have on the microenvironment and two types of interstitial cells: macrophages and fibroblasts. Depending on their behaviour, these cells can either help maintain and restore normal function or foster chronic disease progression. When macrophages and fibroblasts dysregulate, it leads to chronic low-grade inflammation, fibrosis, and eventually damage to parenchymal (organ-specific) cells. The sixth network considers how macrophages change phenotype. Thus, a pathway is identified through this hierarchical network to reveal how external factors and lifestyle affect interstitial cell behaviour. This theory can be tested and it needs to be tested because, if correct, it has profound implications. Not only does this theory explain how chronic low-grade inflammation causes chronic disease progression, it also provides insight into salutogenesis, or the process by which health is maintained and restored. Understanding low-grade inflammation as a stalled healing process offers a new strategy for chronic disease management. Rather than treating each chronic disease separately by a focus on parenchymal pathology, a salutogenic strategy of optimizing interstitial health could prevent and mitigate multiple chronic diseases simultaneously.

The Mechanism of Wnt Pathway Regulated by Telocytes to Promote the Regeneration and Repair of Intrauterine Adhesions.

Background Telocytes (TCs), a novel interstitial cell type in the reproductive tract, participating in pathophysiology of intrauterine adhesions (IUA). This study further investigates the hypothesis that TCs, a source of Wnt, promote the regeneration and repair of IUA. Methods RNA sequencing datasets of IUA patient (GSE160633) and mouse intestine mesenchymal cells (GSE94072) in GEO database were analyzed for differentially expressed genes (DEGs), and quantitative real-time PCR (qRT-PCR) measured indicated gene expression in TC-educated endometrial stromal cells (ESCs) and noneducated ESCs and verified the results of data mining from GEO database. Results The expression levels of Wnt genes were downregulated in IUA compared to the control and were upregulated in TCs. In particular, the changes of Wnt5a expression level were the most significant (logFC = 4.0314 and adjusted P value = 0.0023), and the relative Wnt5a expression level was remarkably higher in TC-educated ESCs than noneducated ESCs verified by qRT-PCR (P = 0.0027). Conclusions TCs may enhance the regeneration and repair of IUA through the Wnt signaling pathway.

CD34 is Expressed in Endothelial Cells in Embryonic Testes and is Additionally Expressed in Non-Endothelial Cells in Postnatal Mouse Testes.

CD34 is expressed in various cell types in various tissues/organs, and has been regarded as being expressed in progenitors in various differentiation pathways. On the other hand, morphological studies have reported the presence of a special type of interstitial cells, telocytes, which generally express CD34, and have extremely long moniliform prolongations in various tissues/organs in vertebrates. We have recently reported the successful reconstruction of testicular structures by 3-D re-aggregation culture of dissociated prepubertal mouse testicular cells, and the roles of CD34 + cells in the reconstruction. However, it was unknown whether CD34 is expressed in embryonic through adult testes, and if so, in what cell type it is expressed. In order to clarify the expression of CD34 and behavior of CD34 + cells during development of mouse testes, we performed immunohistochemical studies. The results show that CD34 is expressed in two cell types in testes; one is endothelial cells which co-express CD31, VE-cadherin, and integrin β1, but barely express PDGFRα and integrin α4 and α9, throughout development, while the other one is non-endothelial cells in which CD34 expression is initiated after birth, and which co-express PDGFRα and integrin α4, α9, and β1. The latter corresponds to telocytes. The present findings will lead to clarifying the roles of these two types of CD34 + cells in spermatogenesis.

The complex role of telocytes in female prostate tumorigenesis in a rodent model.

The prostate is not an organ exclusive to the male. It is also found in females of several species, including humans, in which part of the Skene gland is homologous to the male prostate. Evidence is accumulating that changes in the stroma are central to tumorigenesis. Equally, telocytes, a recently discovered type of interstitial cell, are essential for the maintenance of stromal organization. However, it is still uncertain whether there are telocytes in the female prostate and if they play a role in tumorigenesis. The present study used ultrastructural and immunofluorescence techniques to investigate the presence of telocytes in the prostate of Mongolian gerbil females, a rodent model that often has a functional prostate in females, as well as to assess the impact of a combination of N-ethyl-N-nitrosourea, testosterone, and estradiol on telocytes. The results point to the presence of telocytes in the female prostate in the perialveolar and interalveolar regions, and reveal that these cells are absent in regions of benign and premalignant lesions in the gland, in which the perialveolar smooth muscle is altered. Additionally, telocytes are also closely associated with infiltrated immune cells in the stroma. Our data suggest that telocytes are important for both the maintenance of smooth muscle and prostatic epithelium integrity, which indicates a protective role against the advancement of tumorigenesis. But telocytes are also associated with immune cells and a proinflammatory/proangiogenic role for these cells cannot be ruled out, implying that telocytes have a complex role in prostatic tumorigenesis in females.

Human derived tendon cells contribute to myotube formation in vitro

Skeletal muscle possesses remarkable adaptability to mechanical loading and regenerative potential following muscle injury primarily due to satellite cell activity. Although the roles of several types of interstitial cells in skeletal muscle have been documented, the signaling interplay between the skeletal muscle and the adjacent tendon tissue has not been elucidated. Here, we tested whether human tendon derived cells (tenocytes) could induce human myogenic cells (myoblasts) proliferation and differentiation in vitro using co-culture experiments that allowed us to investigate the effect of tenocytes secretion upon myogenic progression. This was done in vitro by introducing insert wells with either myoblasts, tenocytes, or no cells (control) into a myoblast containing well (co-culture). Immunofluorescence analysis revealed a higher fusion index (≥5 nuclei within one Desmin + myotube) and a higher myotube diameter in co-cultures with tenocytes compared to myoblasts condition. Correspondingly, MHC-IIX gene expression was up-regulated when co-cultured with tenocytes. However, the proliferation of myoblasts (either Ki67 or BrdU + cells) was not enhanced under the presence of tenocytes. These findings show that tenocytes influence myotube formation upon human primary cells in vitro and contribute to understanding the role of tendon derived cells in skeletal muscle during development and regeneration.

The hyperpolarization-activated, cyclic nucleotide-gated channel resides on myocytes in mouse bladders and contributes to adrenergic-induced detrusor relaxation.

Control of urinary continence is predicated on sensory signaling about bladder volume. Bladder sensory nerve activity is dependent on tension, implicating autonomic control over detrusor myocyte activity during bladder filling. Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels are known contributors to bladder control, but their mechanism of action is not well understood. The lack of a definitive identification of cell type(s) expressing HCN in the bladder presents a significant knowledge gap. We recently reported a complete transcriptomic atlas of the C57BL/6 mouse bladder showing the dominant HCN paralog in mouse bladder, Hcn1, is limited to a subpopulation of detrusor smooth myocytes (DSMs). Here, we report details of these findings, along with results of patch-clamp experiments, immunohistochemistry, and functional myobath/tension experiments in bladder strips. With the use of a transgenic mouse expressing fluorescence-tagged α-smooth muscle actin, our data confirmed location and function of DSM HCN channels. Despite previous associations of HCN with postulated bladder interstitial cells, neither evidence of specific interstitial cell types nor an association of nonmyocytes with HCN was discovered. We confirm that HCN activation participates in reducing sustained (tonic) detrusor tension via cAMP, with no effect on intermittent (phasic) detrusor activity. In contrast, blockade of HCN increases phasic activity induced by a protein kinase A (PKA) blocker or a large-conductance Ca2+-activated K+ (BK) channel opener. Our findings, therefore, suggest a central role for detrusor myocyte HCN in regulating and constraining detrusor myocyte activity during bladder filling.