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Chen X.,Fudan University | Zheng Y.,Shanghai JiaoTong University | Manole C.G.,University of Bucharest | Manole C.G.,National Institute of Pathology | And 2 more authors.
Journal of Cellular and Molecular Medicine | Year: 2013

Telocytes (TCs), a new type of interstitial cells, were identified in many different organs and tissues of mammalians and humans. In this study, we show the presence, in human oesophagus, of cells having the typical features of TCs in lamina propria of the mucosa, as well as in muscular layers. We used transmission electron microscopy (TEM), immunohistochemistry (IHC) and primary cell culture. Human oesophageal TCs present a small cell body with 2-3 very long Telopodes (Tps). Tps consist of an alternation of thin segments (podomers) and thick segments (podoms) and have a labyrinthine spatial arrangement. Tps establish close contacts ('stromal synapses') with other neighbouring cells (e.g. lymphocytes, macrophages). The ELISA testing of the supernatant of primary culture of TCs indicated that the concentrations of VEGF and EGF increased progressively. In conclusion, our study shows the existence of typical TCs at the level of oesophagus (mucosa, submucosa and muscular layer) and suggests their possible role in tissue repair. © 2013 The Authors.


PubMed | French Institute of Health and Medical Research, Lebanese University, National Institute of Pathology and Sainte Therese Hospital
Type: Journal Article | Journal: Molecular and clinical oncology | Year: 2016

Lung cancer is most prevalent human cancer worldwide. However, no molecular markers are currently available for predicting lung cancer prognosis. Therefore, identifying novel biomarkers may be useful for improving clinical diagnosis and patient stratification. Krppel-like factor 4 (KLF4) is a transcription factor with opposing roles in different human cancers. Its overexpression in several cancers is correlated with a poor prognosis. However, the expression and role of KLF4 in lung cancer remains to be elucidated. The aim of this study was to determine the profile of KLF4 expression in different types of lung cancer. The KLF4 protein expression level was tested and evaluated by immunohistochemical analysis in 47 lung tumors and normal tissues, and then correlated with clinical characteristics. A differential expression of KLF4 was observed between normal tissue and each of the lung cancer types. A significant decrease in KLF4 expression was observed in non-small-cell lung cancer (NSCLC) compared with that in normal tissue, while significant overexpression was detected in small-cell lung cancer. Furthermore, a higher rate of expression was observed in stage II, III and IV disease compared with stage I disease in NSCLC tissues. KLF4 expression was not found to be associated with age or gender. Our results suggested that the KLF4 protein level may be a potential biomarker in patients with advanced lung cancer.


Suciu L.,Carol Davila University of Medicine and Pharmacy | Suciu L.,National Institute of Pathology | Popescu L.M.,Carol Davila University of Medicine and Pharmacy | Popescu L.M.,National Institute of Pathology | And 8 more authors.
Cells Tissues Organs | Year: 2010

In the last few years, a new cell type - interstitial Cajal-like cell (ICLC) - has been described in digestive and extra-digestive organs. The name has recently been changed to telocytes (TC) and their typical thin, long processes have been named telopodes (TP). To support the hypothesis that TC may also be present in human placenta and add to the information already available, we provide evidence on the ultrastructure, immunophenotype, distribution, and interactions with the surrounding stromal cells of TC in the villous core of human term placenta. We used phase-contrast microscopy, light microscopy of semithin sections, transmission electron microscopy, immunohistochemistry, and immunofluorescence of tissue sections or cell cultures, following a pre-established diagnostic algorithm. Transmission electron microscopy showed cells resembling TC, most (∼76%) having 2-3 very thin, longprocesses (tens to hundreds of micrometers), with an uneven calibre(≤0.5 μm thick) and typical branching pattern. The dilations of processes accommodate caveolae, endoplasmic reticulum cisternae, and mitochondria. These TC have close contacts with perivascular SMC in stem villi. In situ, similar cells are positive for c-kit, CD34, vimentin, caveolin-1, vascular endothelial growth factor (VEGF), and inducible nitric oxide synathase (iNOS). The c-kit-positive cells inconsistently co-express CD34, CD44, αSMA, S100, neuron-specific enolase, and nestin. Among cells with a morphologic TC profile in cell cultures, about 13% co-express c-kit, vimentin, and caveolin-1; 70% of the c-kit-positive cells co-express CD34 and 12% co-express iNOS or VEGF. In conclusion, this study confirms the presence of TC in human term placenta and provides their ultrastructural and immunophenotypic characterization. © 2010 S. Karger AG, Basel.


Nader L.,Saint - Joseph University | Lahoud L.,National Institute of Pathology | Chouery E.,Saint - Joseph University | Aftimos G.,Saint - Joseph University | And 2 more authors.
Annales de Cardiologie et d'Angeiologie | Year: 2010

Brain natriuretic peptide (BNP) binds to three types of natriuretic peptide receptors, NPR-A, -B and -C (NPRs). The expression shape of BNP and NPRs seems to be an important modulator factor in the pathogenesis of cardiac hypertrophy. The aim of this study was to evaluate the expression of NPRs in an animal model of pressure overload hypertrophy. Left ventricular hypertrophy was induced by chronic abdominal aortic banding in adult male Wistar rats. After six weeks, NPRs gene expression was evaluated with RT-PCR, BNP plasma concentration and BNP positive myocytes were measured with ELISA and immunohistochemistry techniques respectively. NPR-A and NPR-C mRNA expression was significantly increased in left ventricular hypertrophied cardiomyocytes by 1.6-fold and 2.1-fold respectively (P<0.01). Abdominal aortic banding increased significantly BNP plasma concentration (630 ± 8 pg/ml vs 106 ± 4 pg/ml; P< 0.01). The percentage of BNP positive cells in normal myocardial tissue were 40% while in the hypertrophied one it raised to 80%. The data suggest that in our left ventricular hypertrophy model, the NPR-A and NPR-C receptors were increased in association to the increased BNP level. This relationship may amplify beneficial paracrine/autocrine effects of BNP on cardiac remodelling in response to hemodynamic overload. © 2009 Elsevier Masson SAS.


Raducanu A.,National Institute for Energy Research and Development ICEMENERG | Codorean E.,National Institute of Pathology | Grigoriu C.,Institute for Laser | Meghea A.,Polytechnic University of Bucharest
UPB Scientific Bulletin, Series B: Chemistry and Materials Science | Year: 2011

Workplace dusts generated in power plants, with particular reference to thermal power of Mintia - Deva have been studied. In order to determine the chemical composition of powder structural analysis was used by corroborating data obtained by elemental analysis performed by two methods: atomic absorption spectrometry and SEM-EDAX. Dust collected from various locations in power plant contained more than 25% SiO 2, 4% Al2O3 10% Fe2O3. The impact of these particles on health workers in these different workplaces was assessed by specific biochemical and hematological tests. The level of cytokines was proposed as an indicator for the inflammatory processes associated with exposure to occupational hazards.


Cismasiu V.B.,Victor Babes National Institute of Pathology | Popescu L.M.,Victor Babes National Institute of Pathology | Popescu L.M.,University of Bucharest | Popescu L.M.,National Institute of Pathology
Journal of Cellular and Molecular Medicine | Year: 2015

Telocytes (TCs) are cells ubiquitously distributed in the body and characterized by very long and thin prolongations named telopodes (Tps). Cardiac TCs are the best characterized TCs for the moment. Tps release extracellular vesicles (EVs) in vivo and in vitro suggesting that TCs regulate the activity of other cells by vesicular paracrine signals. TCs have been found within the stem cell niche of several organs. Electron microscopy or electron tomography has shown that Tps are located in close vicinity of stem cells (SC). Since stem cell regulation by niche components involves paracrine signalling, we have investigated if TCs could be part of this mechanism. Using fluorescent labelling of cells and EVs with calcein and Cy5-miR-21 oligos, we provide evidence that TCs can modulate SC through EVs loaded with microRNAs. TCs deliver microRNA to cardiac stem cells (CSCs), as well as to other types of SCs (e.g. hematopoietic SC) indicating that this mechanism is not restricted to cardiac tissue. We also found that CSCs deliver microRNA loaded EVs to TCs, suggesting that there is a continuous, post-transcriptional regulatory signal back and forth between TCs and SC. In conclusion, our data reveal the existence of a reciprocal (bidirectional) epigenetic signalling between TCs and SC. © 2015 The Authors.


Saliba Y.,Saint - Joseph University | Karam R.,Saint - Joseph University | Smayra V.,Saint - Joseph University | Aftimos G.,National Institute of Pathology | And 3 more authors.
Journal of the American Society of Nephrology | Year: 2015

Transient receptor potential canonical (TRPC) Ca2+-permeant channels, especially TRPC3, are increasingly implicated in cardiorenal diseases. We studied the possible role of fibroblast TRPC3 in the development of renal fibrosis. In vitro, a macromolecular complex formed by TRPC1/TRPC3/TRPC6 existed in isolated cultured rat renal fibroblasts. However, specific blockade of TRPC3 with the pharmacologic inhibitor pyr3 was sufficient to inhibit both angiotensin II-and 1-oleoyl-2-acetyl-sn-glycerolinduced Ca2+ entry in these cells, which was detected by fura-2 Ca2+ imaging. TRPC3 blockade or Ca2+ removal inhibited fibroblast proliferation andmyofibroblast differentiation by suppressing the phosphorylation of extracellular signalregulated kinase (ERK1/2). In addition, pyr3 inhibited fibrosis and inflammation-associated markers in a noncytotoxic manner. Furthermore, TRPC3 knockdown by siRNA confirmed these pharmacologic findings. In adult Male Wistar rats or wild-type mice subjected to unilateral ureteral obstruction, TRPC3 expression increased in the fibroblasts of obstructed kidneys and was associated with increased Ca2+ entry, ERK1/2 phosphorylation, and fibroblast proliferation. Both TRPC3 blockade in rats and TRPC3 knockout in mice inhibited ERK1/2 phosphorylation and fibroblast activation as well as myofibroblast differentiation and extracellular matrix remodeling in obstructed kidneys, thus ameliorating tubulointerstitial damage and renal fibrosis. In conclusion, TRPC3 channels are present in renal fibroblasts and control fibroblast proliferation, differentiation, and activation through Ca2+-mediated ERK signaling. TRPC3 channelsmight constitute important therapeutic targets for improving renal remodeling in kidney disease. © 2015 by the American Society of Nephrology.


Popescu L.M.,Carol Davila University of Medicine and Pharmacy | Popescu L.M.,National Institute of Pathology | Manole C.G.,Carol Davila University of Medicine and Pharmacy | Manole C.G.,National Institute of Pathology | And 7 more authors.
Journal of Cellular and Molecular Medicine | Year: 2010

The existence of the epicardial telocytes was previously documented by immunohistochemistry (IHC) or immunofluorescence. We have also demonstrated recently that telocytes are present in mice epicardium, within the cardiac stem-cell niches, and, possibly, they are acting as nurse cells for the cardiomyocyte progenitors. The rationale of this study was to show that telocytes do exist in human (sub)epicardium, too. Human autopsy hearts from 10 adults and 15 foetuses were used for conventional IHC for c-kit/CD117, CD34, vimentin, S-100, τ, Neurokinin 1, as well as using laser confocal microscopy. Tissue samples obtained by surgical biopsies from 10 adults were studied by digital transmission electron microscopy (TEM). Double immunolabelling for c-kit/CD34 and, for c-kit/vimentin suggests that in human beings, epicardial telocytes share similar immunophenotype features with myocardial telocytes. The presence of the telocytes in human epicardium is shown by TEM. Epicardial telocytes, like any of the telocytes are defined by telopodes, their cell prolongations, which are very long (several tens of μm), very thin (0.1-0.2 μm, below the resolving power of light microscopy) and with moniliform configuration. The interconnected epicardial telocytes create a 3D cellular network, connected with the 3D network of myocardial telocytes. TEM documented that telocytes release shed microvesicles or exocytotic multivesicular bodies in the intercellular space. The human epicardial telocytes have similar phenotype (TEM and IHC) with telocytes located among human working cardiomyocyte. It remains to be established the role(s) of telocytes in cardiac renewing/repair/regeneration processes, and also the pathological aspects induced by their 'functional inhibition', or by their variation in number. We consider telocytes as a real candidate for future developments of autologous cell-based therapy in heart diseases. © 2010 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.


Mandache E.,National Institute of Pathology | Gherghiceanu M.,National Institute of Pathology | Macarie C.,Institute for Cardiovascular Diseases | Kostin S.,Max Planck Institute for Heart and Lung Research | And 2 more authors.
Journal of Cellular and Molecular Medicine | Year: 2010

The human heart can be frequently affected by an organ-limited amyloidosis called isolated atrial amyloidosis (IAA). IAA is a frequent histopathological finding in patients with long-standing atrial fibrillation (AF). The aim of this paper was to investigate the ultrastructure of cardiomyocytes and telocytes in patients with AF and IAA. Human atrial biopsies were obtained from 37 patients undergoing cardiac surgery, 23 having AF (62%). Small fragments were harvested from the left and right atrial appendages and from the atrial sleeves of pulmonary veins and processed for electron microscopy (EM). Additional fragments were paraffin embedded for Congo-red staining. The EM examination certified that 17 patients had IAA and 82% of them had AF. EM showed that amyloid deposits, composed of characteristic 10-nm-thick filaments were strictly extra-cellular. Although, under light microscope some amyloid deposits seemed to be located within the cardiomyocyte cytoplasm, EM showed that these deposits are actually located in interstitial recesses. Moreover, EM revealed that telopodes, the long and slender processes of telocytes, usually surround the amyloid deposits limiting their spreading into the interstitium. Our results come to endorse the presumptive association of AF and IAA, and show the exclusive, extracellular localization of amyloid fibrils. The particular connection of telopodes with amyloid deposits suggests their involvement in isolated atrial amyloidosis and AF pathogenesis. © 2010 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.


Barile L.,Fondazione Cardiocentro Ticino | Gherghiceanu M.,National Institute of Pathology | Popescu L.M.,National Institute of Pathology | Moccetti T.,Fondazione Cardiocentro Ticino | And 2 more authors.
Stem Cells International | Year: 2013

Cardiospheres (CSs) are self-assembling multicellular clusters from the cellular outgrowth from cardiac explants cultured in nonadhesive substrates. They contain a core of primitive, proliferating cells, and an outer layer of mesenchymal/stromal cells and differentiating cells that express cardiomyocyte proteins and connexin 43. Because CSs contain both primitive cells and committed progenitors for the three major cell types present in the heart, that is, cardiomyocytes, endothelial cells, and smooth muscle cells, and because they are derived from percutaneous endomyocardial biopsies, they represent an attractive cell source for cardiac regeneration. In preclinical studies, CS-derived cells (CDCs) delivered to infarcted hearts resulted in improved cardiac function. CDCs have been tested safely in an initial phase-1 clinical trial in patients after myocardial infarction. Whether or not CDCs are superior to purified populations, for example, c-kit+ cardiac stem cells, or to gene therapy approaches for cardiac regeneration remains to be evaluated. © 2013 Lucio Barile et al.

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