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1.
Sci Rep ; 14(1): 14904, 2024 06 28.
Article in English | MEDLINE | ID: mdl-38942924

ABSTRACT

Telocytes are closely associated with the regulation of tissue smooth muscle dynamics in digestive system disorders. They are widely distributed in the biliary system and exert their influence on biliary motility through mechanisms such as the regulation of CCK and their electrophysiological effects on smooth muscle cells. To investigate the relationship between telocytes and benign biliary diseases,such as gallbladder stone disease and biliary dilation syndrome, we conducted histopathological analysis on tissues affected by these conditions. Additionally, we performed immunohistochemistry and immunofluorescence double staining experiments for telocytes. The results indicate that the quantity of telocytes in the gallbladder and bile duct is significantly lower in pathological conditions compared to the control group. This reveals a close association between the decrease in telocyte quantity and impaired gallbladder motility and biliary fibrosis. Furthermore, further investigations have shown a correlation between telocytes in cholesterol gallstones and cholecystokinin-A receptor (CCK-AR), suggesting that elevated cholesterol levels may impair telocytes, leading to a reduction in the quantity of CCK-AR and ultimately resulting in impaired gallbladder motility.Therefore, we hypothesize that telocytes may play a crucial role in maintaining biliary homeostasis, and their deficiency may be associated with the development of benign biliary diseases, including gallstone disease and biliary dilation.


Subject(s)
Cholelithiasis , Gallbladder , Telocytes , Telocytes/metabolism , Telocytes/pathology , Cholelithiasis/pathology , Cholelithiasis/metabolism , Humans , Gallbladder/pathology , Gallbladder/metabolism , Female , Male , Bile Ducts/pathology , Bile Ducts/metabolism , Middle Aged , Aged , Dilatation, Pathologic
2.
DNA Cell Biol ; 43(7): 341-352, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38634821

ABSTRACT

Telocytes have some cytoplasmic extensions called telopodes, which are thought to play a role in mitochondrial transfer in intercellular communication. Besides, it is hypothesized that telocytes establish cell membrane-mediated connections with breast cancer cells in coculture and may contribute to the survival of neoplastic cell clusters together with other stromal cells. The aim of this study is to investigate the contribution of telocytes and telocyte-derived mitochondria, which have also been identified in breast tumors, to the tumor development of breast cancer stem cells (CSCs) via miR-146a-5p. The isolation/characterization of telocytes from bone marrow mononuclear cells and the isolation of mitochondria from these cells were performed, respectively. In the next step, CSCs were isolated from the MDA-MB-231 cell line and were characterized. Then, miR-146a-5p expressions of CSCs were inhibited by anti-miR-146a-5p. The epithelial-mesenchymal transition (EMT) was determined by evaluating changes in vimentin protein levels and was evaluated by analyzing BRCA1, P53, SOX2, E-cadherin, and N-cadherin gene expression changes. Our results showed that miR-146a promoted stemness and oncogenic properties in CSCs. EMT (N-cadherin, vimentin, E-cadherin) and tumorigenic markers (BRCA1, P53, SOX2) of CSCs decreased after miR-146a inhibition. Bone marrow-derived telocytes and mitochondria derived from telocytes favored the reduction of CSC aggressiveness following this inhibition.


Subject(s)
Breast Neoplasms , Coculture Techniques , MicroRNAs , Mitochondria , Neoplastic Stem Cells , Telocytes , Humans , Telocytes/metabolism , Telocytes/pathology , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Mitochondria/metabolism , Mitochondria/pathology , Cell Line, Tumor , Female , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Carcinogenesis/pathology , Carcinogenesis/genetics , Carcinogenesis/metabolism
3.
Cell Mol Gastroenterol Hepatol ; 18(2): 101347, 2024.
Article in English | MEDLINE | ID: mdl-38670488

ABSTRACT

BACKGROUND & AIM: Telocytes, a recently identified type of subepithelial interstitial cell, have garnered attention for their potential roles in tissue homeostasis and repair. However, their contribution to gastric metaplasia remains unexplored. This study elucidates the role of telocytes in the development of metaplasia within the gastric environment. METHODS: To investigate the presence and behavior of telocytes during metaplastic transitions, we used drug-induced acute injury models (using DMP-777 or L635) and a genetically engineered mouse model (Mist1-Kras). Lineage tracing via the Foxl1-CreERT2;R26R-tdTomato mouse model was used to track telocyte migratory dynamics. Immunofluorescence staining was used to identify telocyte markers and evaluate their correlation with metaplasia-related changes. RESULTS: We confirmed the existence of FOXL1+/PDGFRα+ double-positive telocytes in the stomach's isthmus region. As metaplasia developed, we observed a marked increase in the telocyte population. The distribution of telocytes expanded beyond the isthmus to encompass the entire gland and closely reflected the expansion of the proliferative cell zone. Rather than a general response to mucosal damage, the shift in telocyte distribution was associated with the establishment of a metaplastic cell niche at the gland base. Furthermore, lineage-tracing experiments highlighted the active recruitment of telocytes to the emerging metaplastic cell niche, and we observed expression of Wnt5a, Bmp4, and Bmp7 in PDGFRα+ telocytes. CONCLUSIONS: These results suggest that telocytes contribute to the evolution of a gastric metaplasia niche. The dynamic behavior of these stromal cells, their responsiveness to metaplastic changes, and potential association with Wnt5a, Bmp4, and Bmp7 signaling emphasize the significance of telocytes in tissue adaptation and repair.


Subject(s)
Bone Morphogenetic Protein 4 , Gastric Mucosa , Metaplasia , Receptor, Platelet-Derived Growth Factor alpha , Telocytes , Wnt-5a Protein , Animals , Metaplasia/pathology , Mice , Telocytes/metabolism , Telocytes/pathology , Wnt-5a Protein/metabolism , Gastric Mucosa/pathology , Gastric Mucosa/metabolism , Bone Morphogenetic Protein 4/metabolism , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Stomach/pathology , Bone Morphogenetic Protein 7/metabolism , Cell Movement , Mice, Transgenic , Disease Models, Animal , Forkhead Transcription Factors
4.
Am J Dermatopathol ; 46(6): 346-352, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38574066

ABSTRACT

ABSTRACT: Some authors have suggested that the fibroblasts of the nail mesenchyme (onychofibroblasts) can be distinguished from skin fibroblasts by their high expression of CD10. My 2015 study documented the presence of a relatively sparse CD34 + /CD10 + dendritic subpopulation in the dermis and hypodermis of the matrix. For some time now, my hypothesis has been that these interstitial dendritic mesenchymal cells of the matrix correspond to telocytes. Telocytes have been described as peculiar interstitial dendritic cells present in the mesenchymal tissue of numerous organs, including the skin, but their presence and characteristics in the nail unit have not been explored. This study was undertaken to more comprehensively investigate the existence and characteristics of nail telocytes. A series of 20 normal adult nail units were examined with a combination of morphological and immunohistochemical analyses. The matrix dermis contained a sparse subpopulation of CD34 + /CD10 + elongated telocytes with a higher density in the lunular region and, at this distal level, a change in their immunohistochemical profile, resulting in a progressive loss of CD34 expression. The matrix hypodermis showed CD34 + /CD10 + telocytes in their classical elongated aspect, which acquired, especially in the distal fibromyxoid area of the thumb, an oval to round morphology with multiple intracytoplasmic vacuoles. The characteristic dynamic immunophenotypic profile of the dermal telocytes with a progressive distal loss of the defining molecule CD34 was equally observed in the distal hypodermis. The nail bed dermis was thick with a dense fibrous connective tissue. A reticular network of CD34 - /CD10 + telocytes was present in the superficial dermis of the proximal nail bed. The mesenchymal cells of the deep part of the proximal nail bed dermis and the entire distal nail bed dermis were CD34 - /CD10 - . The adult nail mesenchyme is composed of 3 microanatomically distinct regions. Only the thumb has a distal hypodermis rich in mucinous material. The population of telocytes is relatively sparse compared with the fibroblastic population of the entire nail mesenchyme. The concept of onychodermis/onychofibroblasts is not valid. Nail telocytes have a dynamic immunohistochemical profile depending on whether they are located proximally or distally. The CD34 + /CD10 + profile correlates with the onychogenic epithelial region, while the CD34 - /CD10 + profile correlates with a spatial rearrangement of the nail epidermal bed.


Subject(s)
Immunohistochemistry , Nails , Telocytes , Humans , Telocytes/pathology , Nails/pathology , Adult , Antigens, CD34/analysis , Antigens, CD34/metabolism , Female , Male , Middle Aged , Fibroblasts/pathology , Biomarkers/analysis , Biomarkers/metabolism , Aged
5.
Cardiovasc Pathol ; 70: 107617, 2024.
Article in English | MEDLINE | ID: mdl-38309490

ABSTRACT

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


Subject(s)
Aorta, Thoracic , Aortic Dissection , Homeostasis , Microscopy, Electron, Transmission , Telocytes , Humans , Telocytes/pathology , Telocytes/metabolism , Telocytes/ultrastructure , Aortic Dissection/pathology , Aortic Dissection/physiopathology , Aortic Dissection/metabolism , Aorta, Thoracic/pathology , Aorta, Thoracic/metabolism , Male , Middle Aged , Aged , Adventitia/pathology , Adventitia/metabolism , Aortic Aneurysm, Thoracic/pathology , Aortic Aneurysm, Thoracic/metabolism , Aortic Aneurysm, Thoracic/physiopathology , Female , Telopodes/pathology , Telopodes/metabolism , Adult , Fluorescent Antibody Technique , Case-Control Studies
6.
Medicine (Baltimore) ; 102(46): e35983, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37986278

ABSTRACT

Telocytes are a new type of interstitial cell with a diverse morphology and important functions, such as mechanical support, signal transduction, immune regulation, and tissue repair. In this paper, the origin and physiological and pathological functions of telocytes as well as their role in inflammation will be discussed, and the functions and targets of telocytes in inflammation will be fully reviewed, which may contribute to a new therapeutic strategy for inflammatory diseases in the future.


Subject(s)
Telocytes , Humans , Telocytes/pathology , Inflammation/pathology , Signal Transduction
7.
Histochem Cell Biol ; 160(1): 11-25, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37014442

ABSTRACT

Experimental autoimmune encephalomyelitis (EAE) is a classical animal model of human multiple sclerosis (MS) that is most commonly used to study the neuropathology and therapeutic effects of the disease. Telocytes (TCs) are a specialized type of interstitial or mesenchymal cell first identified by Popescu in various tissues and organs. However, the existence, distribution and role of CD34+ stromal cells (SCs)/TCs in the EAE-induced mouse spleen remain to be elucidated. We conducted immunohistochemistry, immunofluorescence (double staining for CD34 and c-kit, vimentin, F4/80, CD163, Nanog, Sca-1, CD31 or tryptase) and transmission electron microscopy experiments to investigate the existence, distribution and role of CD34+ SCs/TCs in the EAE-induced mouse spleen. Interestingly, immunohistochemistry, double-immunofluorescence, and transmission electron microscopy results revealed that CD34+ SCs/TCs were significantly upregulated in the EAE mouse spleen. Immunohistochemical or double-immunofluorescence staining of CD34+ SCs/TCs showed positive expression for CD34, c-kit, vimentin, CD34/vimentin, c-kit/vimentin and CD34/c-kit, and negative expression for CD31 and tryptase. Transmission electron microscopy (TEM) results demonstrated that CD34+ SCs/TCs established close connections with lymphocytes, reticular cells, macrophages, endothelial cells and erythrocytes. Furthermore, we also found that M1 (F4/80) or M2 (CD163) macrophages, and haematopoietic, pluripotent stem cells were markedly increased in EAE mice. Our results suggest that CD34+ SCs/TCs are abundant and may play a contributing role in modulating the immune response, recruiting macrophages and proliferation of haematopoietic and pluripotent stem cells following injury to promote tissue repair and regeneration in EAE mouse spleens. This suggests that their transplantation combined with stem cells might represent a promising therapeutic target for the treatment and prevention of multiple autoimmune and chronic inflammatory disorders.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Pluripotent Stem Cells , Telocytes , Animals , Mice , Antigens, CD34/metabolism , Cell Adhesion Molecules/metabolism , Encephalomyelitis, Autoimmune, Experimental/pathology , Endothelial Cells/metabolism , Pluripotent Stem Cells/metabolism , Spleen , Stromal Cells/metabolism , Telocytes/metabolism , Telocytes/pathology , Tryptases/metabolism , Vimentin/metabolism
8.
Actas dermo-sifiliogr. (Ed. impr.) ; 114(3): 229-239, mar. 2023. tab, ilus
Article in English | IBECS | ID: ibc-217030

ABSTRACT

The telocytes (TCs) are novel interstitial cells that have been overlooked for a long time due to their histologic similarity to other stromal cells. TCs can be separated from the stromal cells based on their distinct immunohistochemical, ultrastructural, and molecular features. Functionally, TCs are involved in the tissue renewal, mechanical support, and immune modulation. These cells are also involved in the signal transduction either through their direct interactions with the neighboring cells or through the paracrine signaling via extracellular vesicles. TCs are damaged in several inflammatory and fibrotic conditions such as ulcerative colitis, Crohn's disease, hepatic fibrosis, psoriasis, and systemic sclerosis. The transplantation of TCs in the damaged tissue can promote tissue regeneration. Therefore, enhancing tissue TCs either by their transplantation or by promoting their survival and growth using novel medications represents novel therapeutic strategy in the future. In this review, we addressed several aspects of TCs including their origin, distribution, morphologic features, and functions. We also discussed their involvement of the cutaneous TCs in the development various pathologic conditions (AU)


Los telocitos (TC) son células intersticiales noveles que han sido subvaloradas durante mucho tiempo debido a su similitud histológica con otras células estromales. Los TC pueden separarse de las células estromales debido a sus distintas características inmunohistoquímicas, ultraestructurales y moleculares. A nivel funcional, los TC están implicados en la renovación tisular, el soporte mecánico y la modulación inmune. Dichas células están implicadas también en la transducción de señal, bien mediante sus interacciones directas con las células circundantes, o bien mediante la señalización paracrina, a través de las vesículas extracelulares. Los TC se ven dañados en ciertas situaciones inflamatorias y fibróticas tales como colitis ulcerosa, enfermedad de Crohn, fibrosis hepática, psoriasis y esclerosis sistémica. El trasplante de TC en el tejido dañado puede promover la regeneración tisular. Por tanto, mejorar los TC tisulares mediante trasplante o promoción de su supervivencia y crecimiento, utilizando medicaciones novedosas, representa una estrategia terapéutica innovadora para el futuro. En esta revisión abordamos diversos aspectos de los TC, incluyendo su origen, su distribución, sus características morfológicas y sus funciones. También tratamos la implicación de los TC cutáneos en el desarrollo de diversas situaciones patológicas (AU)


Subject(s)
Humans , Psoriasis/pathology , Telocytes/pathology , Telocytes/ultrastructure , Signal Transduction , Skin/pathology
9.
Actas dermo-sifiliogr. (Ed. impr.) ; 114(3): t229-t239, mar. 2023. ilus, tab
Article in Spanish | IBECS | ID: ibc-217031

ABSTRACT

Los telocitos (TC) son células intersticiales noveles que han sido subvaloradas durante mucho tiempo debido a su similitud histológica con otras células estromales. Los TC pueden separarse de las células estromales debido a sus distintas características inmunohistoquímicas, ultraestructurales y moleculares. A nivel funcional, los TC están implicados en la renovación tisular, el soporte mecánico y la modulación inmune. Dichas células están implicadas también en la transducción de señal, bien mediante sus interacciones directas con las células circundantes, o bien mediante la señalización paracrina, a través de las vesículas extracelulares. Los TC se ven dañados en ciertas situaciones inflamatorias y fibróticas tales como colitis ulcerosa, enfermedad de Crohn, fibrosis hepática, psoriasis y esclerosis sistémica. El trasplante de TC en el tejido dañado puede promover la regeneración tisular. Por tanto, mejorar los TC tisulares mediante trasplante o promoción de su supervivencia y crecimiento, utilizando medicaciones novedosas, representa una estrategia terapéutica innovadora para el futuro. En esta revisión abordamos diversos aspectos de los TC, incluyendo su origen, su distribución, sus características morfológicas y sus funciones. También tratamos la implicación de los TC cutáneos en el desarrollo de diversas situaciones patológicas (AU)


The telocytes (TCs) are novel interstitial cells that have been overlooked for a long time due to their histologic similarity to other stromal cells. TCs can be separated from the stromal cells based on their distinct immunohistochemical, ultrastructural, and molecular features. Functionally, TCs are involved in the tissue renewal, mechanical support, and immune modulation. These cells are also involved in the signal transduction either through their direct interactions with the neighboring cells or through the paracrine signaling via extracellular vesicles. TCs are damaged in several inflammatory and fibrotic conditions such as ulcerative colitis, Crohn's disease, hepatic fibrosis, psoriasis, and systemic sclerosis. The transplantation of TCs in the damaged tissue can promote tissue regeneration. Therefore, enhancing tissue TCs either by their transplantation or by promoting their survival and growth using novel medications represents novel therapeutic strategy in the future. In this review, we addressed several aspects of TCs including their origin, distribution, morphologic features, and functions. We also discussed their involvement of the cutaneous TCs in the development various pathologic conditions (AU)


Subject(s)
Humans , Psoriasis/pathology , Telocytes/pathology , Telocytes/ultrastructure , Signal Transduction , Skin/pathology
10.
Int J Mol Sci ; 24(4)2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36835203

ABSTRACT

Kaposi sarcoma (KS) is an angioproliferative lesion in which two main KS cell sources are currently sustained: endothelial cells (ECs) and mesenchymal/stromal cells. Our objective is to establish the tissue location, characteristics and transdifferentiation steps to the KS cells of the latter. For this purpose, we studied specimens of 49 cases of cutaneous KS using immunochemistry and confocal and electron microscopy. The results showed that delimiting CD34+ stromal cells/Telocytes (CD34+SCs/TCs) in the external layer of the pre-existing blood vessels and around skin appendages form small convergent lumens, express markers for ECs of blood and lymphatic vessels, share ultrastructural characteristics with ECs and participate in the origin of two main types of neovessels, the evolution of which gives rise to lymphangiomatous or spindle-cell patterns-the substrate of the main KS histopathological variants. Intraluminal folds and pillars (papillae) are formed in the neovessels, which suggests they increase by vessel splitting (intussusceptive angiogenesis and intussusceptive lymphangiogenesis). In conclusion, delimiting CD34+SCs/TCs are mesenchymal/stromal cells that can transdifferentiate into KS ECs, participating in the formation of two types of neovessels. The subsequent growth of the latter involves intussusceptive mechanisms, originating several KS variants. These findings are of histogenic, clinical and therapeutic interest.


Subject(s)
Sarcoma, Kaposi , Skin Neoplasms , Stromal Cells , Telocytes , Humans , Antigens, CD34/metabolism , Endothelial Cells/metabolism , Sarcoma, Kaposi/pathology , Skin Neoplasms/pathology , Stromal Cells/metabolism , Stromal Cells/pathology , Telocytes/metabolism , Telocytes/pathology , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology
11.
J Reprod Dev ; 69(2): 87-94, 2023 Apr 03.
Article in English | MEDLINE | ID: mdl-36754390

ABSTRACT

Uterine peristalsis is essential for gamete transport and embryo implantation. It shares the characteristics of spontaneity, rhythmicity, and directivity with gastrointestinal peristalsis. Telocytes, the "interstitial Cajal-like cells" outside the digestive canal, are also located in the uterus and may act as pacemakers. To investigate the possible origin and regulatory mechanism of periodic uterine peristalsis in the human menstrual cycle, telocytes in the myometrium were studied to determine the effect of estradiol on T-type calcium channel regulation. In this study, biopsies of the human myometrium were obtained for cell culture, and double-labeling immunofluorescence screening was used to identify telocytes and T-type calcium channel expression. Intracellular calcium signal measurements and patch-clamp recordings were used to investigate the role of T-type calcium channels in regulating calcium currents with or without estradiol. Our study demonstrates that telocytes exist in the human uterus and express T-type calcium channels. The intracellular Ca2+ fluorescence intensity marked by Fluo-4AM was dramatically decreased by NNC 55-0396, a highly selective T-type calcium channel blocker, but enhanced by estradiol. T-type calcium current amplitude increased in telocytes incubated with estradiol in a dose-dependent manner compared to the control group. In conclusion, our study demonstrated that telocytes exist in the human myometrium, expressing T-type calcium channels and estradiol-enhanced T-type calcium currents, which may be a reasonable explanation for the origin of uterine peristalsis. The role of telocytes in the human uterus as pacemakers and message transfer stations in uterine peristalsis may be worth further investigation.


Subject(s)
Calcium Channels, T-Type , Telocytes , Female , Humans , Myometrium/metabolism , Myometrium/pathology , Calcium Channels, T-Type/metabolism , Calcium Channels, T-Type/pharmacology , Estradiol/pharmacology , Estradiol/metabolism , Calcium/metabolism , Telocytes/metabolism , Telocytes/pathology
12.
Actas Dermosifiliogr ; 114(3): T229-T239, 2023 Mar.
Article in English, Spanish | MEDLINE | ID: mdl-36690154

ABSTRACT

The telocytes (TCs) are novel interstitial cells that have been overlooked for a long time due to their histologic similarity to other stromal cells. TCs can be separated from the stromal cells based on their distinct immunohistochemical, ultrastructural, and molecular features. Functionally, TCs are involved in the tissue renewal, mechanical support, and immune modulation. These cells are also involved in the signal transduction either through their direct interactions with the neighboring cells or through the paracrine signaling via extracellular vesicles. TCs are damaged in several inflammatory and fibrotic conditions such as ulcerative colitis, Crohn's disease, hepatic fibrosis, psoriasis, and systemic sclerosis. The transplantation of TCs in the damaged tissue can promote tissue regeneration. Therefore, enhancing tissue TCs either by their transplantation or by promoting their survival and growth using novel medications represents novel therapeutic strategy in the future. In this review, we addressed several aspects of TCs including their origin, distribution, morphologic features, and functions. We also discussed their involvement of the cutaneous TCs in the development various pathologic conditions.


Subject(s)
Psoriasis , Telocytes , Humans , Telocytes/pathology , Telocytes/ultrastructure , Skin/pathology , Signal Transduction , Psoriasis/pathology , Biology
13.
Arch Gynecol Obstet ; 307(1): 39-49, 2023 01.
Article in English | MEDLINE | ID: mdl-35668319

ABSTRACT

Endometriosis involving the presence and growth of glands and stroma outside the uterine cavity is a common, inflammatory, benign gynecologic disease. Nevertheless, no single theory can exactly account for the pathogenesis of endometriosis. Telocytes, a kind of novel mesenchymal cells, have been suggested to be crucial in promoting angiogenesis and increasing the activity of endometrial interstitial cells and inflammatory cells. Given above roles, telocytes may be considered as the possible pathogenesis of endometriosis. We reviewed the current literature on telocytes. The following aspects were considered: (A) the telocytes' typical characteristics, function, and morphological changes in endometriosis; (B) the potential role of telocytes in endometriosis by impacting the inflammation, invasion, and angiogenesis; (C) telocytes as the potential treatment options for endometriosis.


Subject(s)
Endometriosis , Telocytes , Female , Humans , Endometriosis/pathology , Uterus/pathology , Telocytes/pathology , Inflammation/pathology , Endometrium/pathology
14.
Cell Oncol (Dordr) ; 46(2): 251-264, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36434360

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) cell-derived exosomal LncRNA SNHG16 is highly expressed and associated with poor overall survival of patients. Telocytes (TCs), as novel interstitial cells, have been reported to promote HCC metastasis. Therefore, in our study, we investigated whether a molecular interaction occurred between exosomal LncSNHG16 and TCs in the tumor microenvironment. METHODS: LncSNHG16 expression in HCC tissues and cell lines was measured, and bioinformatics analysis was performed. Exosomes were isolated and purified from HCC cells with LncSNHG16 overexpression/knockdown vectors and cocultured with TCs. Then, markers of the LncSNHG16/miR-942-3p/MMP9 axis were tested in TCs. Transwell assays and cell wound healing assays were designed to examine the invasion and migration of HCC cells after coincubation with TCs. RNA immunoprecipitation (RIP) assays and dual-luciferase gene reporter assays were performed to verify the binding effect of LncSNHG16, miR-942-3p, and MMP9 mRNA. In vivo, experimental animal models were established to confirm the effect of exosomal LncSNHG16-induced MMP9 expression on HCC metastasis. RESULTS: Exosomal LncSNHG16 was phagocytized by TCs and downregulated miR-942-3p, which induced targeted MMP9 upregulation, and it had specific binding sites with miR-942-3p in TCs to facilitate the migration of HCC cells in vitro and in vivo. Exosomal LncSNHG16 was found to act as a competing endogenous RNA of the miR-942-3p/MMP9 axis in TCs. CONCLUSION: Tumour-derived exosomal LncSNHG16 modulates MMP9 via competitively binding to miR-942-3p in TCs, thus promoting the metastasis of HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Matrix Metalloproteinase 9 , MicroRNAs , RNA, Long Noncoding , Telocytes , Animals , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Liver Neoplasms/pathology , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Telocytes/metabolism , Telocytes/pathology , Tumor Microenvironment
15.
Actas Dermosifiliogr ; 114(3): 229-239, 2023 Mar.
Article in English, Spanish | MEDLINE | ID: mdl-36332689

ABSTRACT

The telocytes (TCs) are novel interstitial cells that have been overlooked for a long time due to their histologic similarity to other stromal cells. TCs can be separated from the stromal cells based on their distinct immunohistochemical, ultrastructural, and molecular features. Functionally, TCs are involved in the tissue renewal, mechanical support, and immune modulation. These cells are also involved in the signal transduction either through their direct interactions with the neighboring cells or through the paracrine signaling via extracellular vesicles. TCs are damaged in several inflammatory and fibrotic conditions such as ulcerative colitis, Crohn's disease, hepatic fibrosis, psoriasis, and systemic sclerosis. The transplantation of TCs in the damaged tissue can promote tissue regeneration. Therefore, enhancing tissue TCs either by their transplantation or by promoting their survival and growth using novel medications represents novel therapeutic strategy in the future. In this review, we addressed several aspects of TCs including their origin, distribution, morphologic features, and functions. We also discussed their involvement of the cutaneous TCs in the development various pathologic conditions.


Subject(s)
Psoriasis , Telocytes , Humans , Telocytes/pathology , Telocytes/ultrastructure , Skin/pathology , Signal Transduction , Psoriasis/pathology , Biology
16.
Folia Med Cracov ; 62(3): 101-109, 2022 Sep 15.
Article in English | MEDLINE | ID: mdl-36309835

ABSTRACT

The interstitial cells known as telocytes have been described in various organs. Their role in the normal physiology and pathogenesis of numerous diseases is well known. They have been described in the context of various diseases (gallstone disease, endometriosis, uterine myoma, hydronephrosis, myocardial infraction, psoriasis, etc.), while their impact on inflammation, involvement in angiogenesis, and repair highlights their part in local homeostasis. What is known about their relationship with the immune system? Their secretomes, genome, immune profiles, contacts with surrounding cells, and specific localization allow us to give a possible explanation for their involvement in pathological pathways. This review aims to present the roles and features of telocytes in the context of intestinal immunity (the largest in our body), in the spleen, their interactions with immunocytes, and their place in stem cell niches.


Subject(s)
Interstitial Cells of Cajal , Leiomyoma , Telocytes , Female , Humans , Telocytes/pathology , Inflammation/metabolism , Leiomyoma/pathology , Myocardium/pathology
17.
Int J Mol Sci ; 23(13)2022 Jun 24.
Article in English | MEDLINE | ID: mdl-35806023

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 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.


Subject(s)
Inflammatory Bowel Diseases , Telocytes , Fibrosis , Humans , Inflammatory Bowel Diseases/pathology , Telocytes/pathology
18.
Int J Mol Sci ; 23(11)2022 May 31.
Article in English | MEDLINE | ID: mdl-35682833

ABSTRACT

Oxygen balance is crucial for angiogenesis, immunity, and tissue repair. The human oviduct is essential for reproductive function, and any imbalance in homeostasis leads to fertility disturbances and might be a reason for ectopic pregnancy development. Uterine myoma is a widespread benign tumour, which is often accompanied by infertility. Telocytes have been discussed in the contexts of motility, fibrosis development, and angiogenesis. We observed the oviducts from patients with and without uterine myoma, comparing the expression of HIF-1, HO, VEGF and its receptor, NOS, oestrogen, and progesterone receptors by immunolabeling. The myometrial and oviductal telocytes were also compared in both groups. Biochemical analyses were conducted for FSH, LH, AMH, sFlt, oestrogen, and progesterone in blood samples. Patients with uterine myoma have different expressions of sex steroid receptors and an increased number of telocytes. The decreasing VEFG expression was compensated by the rise in the HIF-1 and NOS expression. Blood biochemical analyses revealed a higher progesterone level and lower AMH in patients with uterine myoma. No differences in sFlt, FSH, and LF were observed. Uterine myoma impacts oviduct oxygen homeostasis and might cause fertility disturbances (uterine and oviductal infertility factors).


Subject(s)
Infertility , Leiomyoma , Myoma , Telocytes , Animals , Estrogens/metabolism , Female , Follicle Stimulating Hormone/metabolism , Homeostasis , Humans , Hypoxia/metabolism , Infertility/metabolism , Leiomyoma/metabolism , Myoma/metabolism , Myoma/pathology , Oviducts/metabolism , Oxygen/metabolism , Pregnancy , Progesterone/metabolism , Telocytes/pathology
19.
Mediators Inflamm ; 2021: 7534601, 2021.
Article in English | MEDLINE | ID: mdl-34373677

ABSTRACT

BACKGROUND: Telocytes (TCs) are a distinct type of interstitial cells that play a vital role in the pathogenesis of ulcerative colitis and colonic tissue hemostasis. The aim of this study was to examine the effect of nanocurcumin (NC) on the morphometric and immunohistochemical characterization of TCs in the ulcerative colitis (UC) rat model. METHODS: Forty rats were randomly divided into control, NC, UC, and UC+NC groups. At the end of the experiment, the colon was dissected and prepared for histopathological and immunohistochemical assessment. Tissue homogenates were prepared for real-time PCR assessment of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-ß) gene expression. Our results revealed extensive mucosal damage with inflammatory cell infiltration, significant reduction of CD34, and vimentin immunostained TCs in the colon of the UC group with significant elevation of expression of IL-6, TNF-α, and TGF-ß. The UC+NC-treated group revealed significant elevation of TC count compared to the UC group besides, a significant reduction of the three gene expression. CONCLUSION: NC successfully targeted the colonic tissue, improved the mucosal lesion, preserve TCs distribution, and count through its anti-inflammatory and fibrinolytic properties.


Subject(s)
Colitis, Ulcerative/pathology , Colon/pathology , Curcumin/chemistry , Nanoparticles/chemistry , Telocytes/pathology , Animals , Colitis , Colon/metabolism , Disease Models, Animal , Fibrinolysis , Gene Expression Regulation , Immunohistochemistry , Inflammation , Interleukin-6/metabolism , Intestinal Mucosa/metabolism , Male , Rats , Rats, Wistar , Spectroscopy, Fourier Transform Infrared , Transforming Growth Factor beta1/biosynthesis , Tumor Necrosis Factor-alpha/metabolism , Vimentin/chemistry
20.
Int J Mol Sci ; 22(14)2021 Jul 08.
Article in English | MEDLINE | ID: mdl-34298962

ABSTRACT

We studied CD34+ stromal cells/telocytes (CD34+SCs/TCs) in pathologic skin, after briefly examining them in normal conditions. We confirm previous studies by other authors in the normal dermis regarding CD34+SC/TC characteristics and distribution around vessels, nerves and cutaneous annexes, highlighting their practical absence in the papillary dermis and presence in the bulge region of perifollicular groups of very small CD34+ stromal cells. In non-tumoral skin pathology, we studied examples of the principal histologic patterns in which CD34+SCs/TCs have (1) a fundamental pathophysiological role, including (a) fibrosing/sclerosing diseases, such as systemic sclerosis, with loss of CD34+SCs/TCs and presence of stromal cells co-expressing CD34 and αSMA, and (b) metabolic degenerative processes, including basophilic degeneration of collagen, with stromal cells/telocytes in close association with degenerative fibrils, and cutaneous myxoid cysts with spindle-shaped, stellate and bulky vacuolated CD34+ stromal cells, and (2) a secondary reactive role, encompassing dermatitis-e.g., interface (erythema multiforme), acantholytic (pemphigus, Hailey-Hailey disease), lichenoid (lichen planus), subepidermal vesicular (bullous pemphigoid), psoriasiform (psoriasis), granulomatous (granuloma annulare)-vasculitis (leukocytoclastic and lymphocytic vasculitis), folliculitis, perifolliculitis and inflammation of the sweat and sebaceous glands (perifolliculitis and rosacea) and infectious dermatitis (verruca vulgaris). In skin tumor and tumor-like conditions, we studied examples of those in which CD34+ stromal cells are (1) the neoplastic component (dermatofibrosarcoma protuberans, sclerotic fibroma and solitary fibrous tumor), (2) a neoplastic component with varying presentation (fibroepithelial polyp and superficial myxofibrosarcoma) and (3) a reactive component in other tumor/tumor-like cell lines, such as those deriving from vessel periendothelial cells (myopericytoma), epithelial cells (trichoepithelioma, nevus sebaceous of Jadassohn and seborrheic keratosis), Merkel cells (Merkel cell carcinoma), melanocytes (dermal melanocytic nevi) and Schwann cells (neurofibroma and granular cell tumor).


Subject(s)
Antigens, CD34/metabolism , Dermatitis/metabolism , Dermis/metabolism , Neoplasm Proteins/metabolism , Skin Neoplasms/metabolism , Telocytes/metabolism , Animals , Dermatitis/pathology , Dermis/pathology , Humans , Skin Neoplasms/pathology , Telocytes/pathology
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