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      Human myometrium – the ultrastructural 3D network of telocytes

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          Abstract

          Telocytes (TCs), a novel type of interstitial cells, were recently described in the interstitial space of tissues ( http://www.telocytes.com). Telocytes TCs have several very long, moniliform extensions, namely telopodes (Tps). However, the functional role(s) of TCs is not yet understood. Successive photomicrographs of ultrathin sections were concatenated to capture the entire length of Tps which usually measure tens to hundreds of micrometres. Besides the podoms (dilations) and podomers (thin segments), ultrastructural features of Tps include the dichotomous branching and establishing homo- and heterocellular contacts. Telopodes make a labyrinthine system by 3D convolution and overlapping, their number being roughly estimated at approximately 20 per 1000 μm 2. Moreover, the presence of extracellular vesicles (shedding vesicles/exosomes) along the Tps suggests an active intercellular signalling (micro- and macromolecules), with possible significance in regulating uterine contractility.

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          Cardiomyocyte Microvesicles Contain DNA/RNA and Convey Biological Messages to Target Cells

          Anders Waldenström, Nina Gennebäck, Urban Hellman … (2012)
          Background Shedding microvesicles are membrane released vesicles derived directly from the plasma membrane. Exosomes are released membrane vesicles of late endosomal origin that share structural and biochemical characteristics with prostasomes. Microvesicles/exosomes can mediate messages between cells and affect various cell-related processes in their target cells. We describe newly detected microvesicles/exosomes from cardiomyocytes and depict some of their biological functions. Methodology/Principal Findings Microvesicles/exosomes from media of cultured cardiomyocytes derived from adult mouse heart were isolated by differential centrifugation including preparative ultracentrifugation and identified by transmission electron microscopy and flow cytometry. They were surrounded by a bilayered membrane and flow cytometry revealed presence of both caveolin-3 and flotillin-1 while clathrin and annexin-2 were not detected. Microvesicle/exosome mRNA was identified and out of 1520 detected mRNA, 423 could be directly connected in a biological network. Furthermore, by a specific technique involving TDT polymerase, 343 different chromosomal DNA sequences were identified in the microvesicles/exosomes. Microvesicle/exosomal DNA transfer was possible into target fibroblasts, where exosomes stained for DNA were seen in the fibroblast cytosol and even in the nuclei. The gene expression was affected in fibroblasts transfected by microvesicles/exosomes and among 333 gene expression changes there were 175 upregulations and 158 downregulations compared with controls. Conclusions/Significance Our study suggests that microvesicles/exosomes released from cardiomyocytes, where we propose that exosomes derived from cardiomyocytes could be denoted “cardiosomes”, can be involved in a metabolic course of events in target cells by facilitating an array of metabolism-related processes including gene expression changes.
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            Telocytes, a distinct type of cell among the stromal cells present in the lamina propria of jejunum.

            L. Popescu, A Simionescu, D Cretoiu … (2012)
            Conventionally, cells described in the stroma of the intestinal wall are fibroblasts/fibrocytes, mast cells, plasma cells, eosinophils, macrophages and, interstitial cells of Cajal (ICCs), the latter being considered as the pacemakers of gastrointestinal rhythmicity. Recently, a new type of stromal cell called telocyte (TCs) was found in various cavitary and non-cavitary organs (www.telocytes.com). We show here direct electron microscopical evidence for the presence of TCs in the lamina propria of rat jejunum just beneath the epithelial layer of the mucosal crypts and in between the smooth muscle cells (SMCs) of muscularis mucosae. TCs are characterized by: several very long (tens to hundreds of µm) prolongations called telopodes (Tps). Tps (with caliber below the resolving power of light microscopy) display podomeres (thin segments ≤ 0.2 µm) and podoms (dilations accommodating caveolae, mitochondria, and endoplasmic reticulum). Tps present dichotomous branching and form a three dimensional network close to immune cells, SMCs or nerve bundles. TCs could play a role in intercellular signaling and control of local tissue homeostasis.
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              Telocytes and putative stem cells in the lungs: electron microscopy, electron tomography and laser scanning microscopy

              Laurențiu Popescu, Mihaela Gherghiceanu, Laura Suciu … (2011)
              This study describes a novel type of interstitial (stromal) cell — telocytes (TCs) — in the human and mouse respiratory tree (terminal and respiratory bronchioles, as well as alveolar ducts). TCs have recently been described in pleura, epicardium, myocardium, endocardium, intestine, uterus, pancreas, mammary gland, etc. (see www.telocytes.com). TCs are cells with specific prolongations called telopodes (Tp), frequently two to three per cell. Tp are very long prolongations (tens up to hundreds of μm) built of alternating thin segments known as podomers (≤ 200 nm, below the resolving power of light microscope) and dilated segments called podoms, which accommodate mitochondria, rough endoplasmic reticulum and caveolae. Tp ramify dichotomously, making a 3-dimensional network with complex homo- and heterocellular junctions. Confocal microscopy reveals that TCs are c-kit- and CD34-positive. Tp release shed vesicles or exosomes, sending macromolecular signals to neighboring cells and eventually modifying their transcriptional activity. At bronchoalveolar junctions, TCs have been observed in close association with putative stem cells (SCs) in the subepithelial stroma. SCs are recognized by their ultrastructure and Sca-1 positivity. Tp surround SCs, forming complex TC-SC niches (TC-SCNs). Electron tomography allows the identification of bridging nanostructures, which connect Tp with SCs. In conclusion, this study shows the presence of TCs in lungs and identifies a TC-SC tandem in subepithelial niches of the bronchiolar tree. In TC-SCNs, the synergy of TCs and SCs may be based on nanocontacts and shed vesicles. Electronic supplementary material The online version of this article (doi:10.1007/s00441-011-1229-z) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Cell Mol Med
                Journal ID (iso-abbrev): J. Cell. Mol. Med
                Journal ID (publisher-id): jcmm
                Title: Journal of Cellular and Molecular Medicine
                Publisher: BlackWell Publishing Ltd (Oxford, UK )
                ISSN (Print): 1582-1838
                ISSN (Electronic): 1582-4934
                Publication date (Print): November 2012
                Publication date (Electronic): 29 October 2012
                Volume: 16
                Issue: 11
                Pages: 2844-2849
                Affiliations
                [a ]Division of Cellular and Molecular Medicine, Department of Morphological Sciences, Carol Davila University of Medicine and Pharmacy Bucharest, Romania
                [b ]Department of Ultrastructural Pathology, Victor Babeş National Institute of Pathology Bucharest, Romania
                [c ]Molecular Medicine Department, Victor Babeş National Institute of Pathology Bucharest, Romania
                [d ]Division of Advanced Studies, Victor Babeş National Institute of Pathology Bucharest, Romania
                Author notes
                *Correspondence to: Prof. L.M. POPESCU, Division of Advanced Studies, Victor Babes National Institute of Pathology, 99-101 Spl. Independentei, Bucharest, Romania. Tel.: +40744535298 E-mail: LMP@ 123456jcmm.org
                Article
                DOI: 10.1111/j.1582-4934.2012.01651.x
                PMC ID: 4118253
                PubMed ID: 23009098
                SO-VID: e6acdb70-f8b5-4413-86d1-de8d5321b3ed
                Copyright © © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
                History
                Date received : 19 July 2012
                Date accepted : 22 September 2012
                Categories
                Subject: Short Communications

                ScienceOpen disciplines: Molecular medicine
                Keywords: telocytes,telopodes,podoms,podomers,human uterus,extracellular vesicles
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: telocytes, telopodes, podoms, podomers, human uterus, extracellular vesicles

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