|
1
|
Ez Elarab SM, Mohamed HM, El-Gendy SAA, El-Mansi AA, Eldesoqui MB, Dawood AF, Alsafy MAM, Rashwan AM. Novel identification of telocytes in the skin of the desert tortoise (Testudo graeca): A correlative study using semithin section, transmission electron microscopy, and immunofluorescence. Res Vet Sci 2025; 191:105689. [PMID: 40345112 DOI: 10.1016/j.rvsc.2025.105689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Revised: 04/23/2025] [Accepted: 05/04/2025] [Indexed: 05/11/2025]
Abstract
This study comprehensively investigates the presence and characteristics of telocytes in the skin of desert tortoises, employing a multifaceted approach that includes light microscopy, transmission electron microscopy (TEM), and immunofluorescence analyses. A groundbreaking revelation is made as our study, for the first time, unveils the existence of telocytes in the skin of the Greek tortoise. The intricate architecture of the skin, comprising scales, a keratin layer, an epidermis, a dermis, and a hypodermis, is meticulously examined. The epidermis, marked by a stratified epithelium and a substantial keratin layer, features a corrugated basement membrane. Notably, the dermis is a significant site housing telocytes, identified by their distinctive rod-shaped morphology and extensive cytoplasmic processes, including a thick podom and a thin podomere containing nanovesicles. Extracellular nanovesicles play a crucial role in facilitating communication between telocytes and melanophores. Utilizing CD34, PDGFRα, and Vimentin markers, we observe the abundance and intensity of CD34, particularly in the central dermis, and the widespread presence of PDGFRα throughout the dermis. Although less abundant near the epidermis and hypodermis, Vimentin increases in the central dermis with reduced intensity compared to CD34 and PDGFRα. Co-expression analyses reveal robust associations between CD34 and PDGFRα, highlighting them as dominant markers in telocytes. This suggests their potential significance in supporting the tortoise's skin health and resilience in harsh desert conditions. The understanding of these molecular dynamics provides insights into the adaptive strategies employed by desert tortoises, emphasizing the therapeutic relevance of these markers in enhancing skin health in challenging environments.
Collapse
Affiliation(s)
- Samar M Ez Elarab
- Department of Histology and Cytology, Faculty of Veterinary Medicine, Alexandria University, Abis 10th P.O., 21944 Alexandria, Egypt
| | - Hagar M Mohamed
- Department of Medical Laboratory Analysis, Faculty of Medical & Health Sciences, Liwa College, Abu Dhabi, United Arab Emirates; Department of Applied Medical Chemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Samir A A El-Gendy
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Alexandria University, Abis 10th P.O., 21944 Alexandria, Egypt
| | - Ahmed A El-Mansi
- Biology Department, Faculty of Science, King Khalid University, Abha 61413, Saudi Arabia
| | - Mamdouh B Eldesoqui
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Diriyah 13713, Riyadh, Saudi Arabia
| | - Amal F Dawood
- Department of Basic Medical Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Mohamed A M Alsafy
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Alexandria University, Abis 10th P.O., 21944 Alexandria, Egypt.
| | - Ahmed M Rashwan
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt; Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
| |
Collapse
|
|
2
|
Gao R, Zhang X, Ju H, Zhou Y, Yin L, Yang L, Wu P, Sun X, Fang H. Telocyte-derived exosomes promote angiogenesis and alleviate acute respiratory distress syndrome via JAK/STAT-miR-221-E2F2 axis. MOLECULAR BIOMEDICINE 2025; 6:21. [PMID: 40198510 PMCID: PMC11979044 DOI: 10.1186/s43556-025-00259-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 02/27/2025] [Accepted: 03/06/2025] [Indexed: 04/10/2025] Open
Abstract
Acute respiratory distress syndrome (ARDS) is characterized by severe respiratory failure and significant inflammation, leading to vascular and epithelial cell damage. The absence of effective pharmacologic treatments underscores the need for novel therapeutic approaches. Telocytes (TCs), a newly identified type of interstitial cells, have shown potential in tissue repair and angiogenesis, particularly through the release of exosomal microRNAs (miRNAs). Exosomes were isolated from LPS (lipopolysaccharide)-stimulated TCs and characterized using western blotting and nanoparticle tracking analysis. The role of exosomal miR-221 in angiogenesis was assessed through tube formation, migration, and proliferation assays in mouse vascular endothelial cells (MVECs). The JAK/STAT pathway's involvement in miR-221 regulation was determined using western blotting and qRT-PCR. A dual-luciferase assay confirmed E2F2 as a direct target of miR-221. ARDS mouse model was established via LPS instillation, and the therapeutic effects of TCs-derived exosomes were evaluated by histopathological scoring, cytokine analysis, and endothelial barrier integrity assays. Our findings demonstrated that exosomes from LPS-stimulated TCs significantly promoted angiogenesis, proliferation, and migration in MVECs. These effects were mediated by miR-221, which downregulated E2F2 expression, an important regulator of endothelial cell functions. The JAK/STAT pathway played a crucial role in miR-221 production, with pathway inhibition reducing miR-221 levels and attenuating its pro-angiogenic effects. In vivo, TCs-derived exosomes reduced lung inflammation and tissue damage in ARDS mice, effects that were reversed by miR-221 inhibition. These results suggested that TCs-derived exosomes promoted angiogenesis and alleviated ARDS through the JAK/STAT-miR-221-E2F2 axis.
Collapse
Affiliation(s)
- Rongrong Gao
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Clinical Center for Biotherapy at Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xu Zhang
- NHC Key Lab of Reproduction Regulation, Shanghai Engineering Research Center of Reproductive Health Drug and Devices, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
- Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
| | - Huihui Ju
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yile Zhou
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Luoyue Yin
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Liuke Yang
- College of Plant Protection, Nanjing Agricultural University, Nanjing, 210000, China
| | - Pinwen Wu
- Department of Anesthesiology, Minhang Hospital, Fudan University, Shanghai, China
| | - Xia Sun
- Department of Anesthesiology, Shanghai Geriatric Medical Center, Shanghai, China.
| | - Hao Fang
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.
- Department of Anesthesiology, Shanghai Geriatric Medical Center, Shanghai, China.
| |
Collapse
|
|
3
|
Jiang H, Tang Y, Liu A, Ren C, Lin W, Liu K, Zhao X, Li Y. Elucidating the preventive and therapeutic effects of cardiac telocytes paracrine microRNAs on ischemic heart disease. Front Cardiovasc Med 2025; 12:1540051. [PMID: 40236257 PMCID: PMC11997980 DOI: 10.3389/fcvm.2025.1540051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 02/24/2025] [Indexed: 04/17/2025] Open
Abstract
Telocytes (TCs), a newly identified type of mesenchymal cell since 2010, possess substantial potential in maintaining tissue homeostasis, orchestrating organ development, and facilitating tissue regeneration. Their distribution in blood, the adventitia of blood vessels, and the intima implies a close association with vascular function. Ischemic heart disease (IHD), a significant challenge in cardiovascular disease, is characterized by the occlusion of major vessels, obstruction of collateral circulation, and disruption of the capillary network-pathological features closely linked to endothelial cell damage. Myocardial tissue is rich in cardiac telocytes (cTCs), which, following myocardial injury, can secrete numerous miRNAs that promote angiogenesis, including miR-let-7e, miR-10a, and miR-126-3p. This indicates that cTCs may have therapeutic potential for IHD. The primary mechanism by which cTCs-derived exosomes exert paracrine effects is through reducing endothelial cell injury, suggesting that enhancing the production of cTCs could offer a novel therapeutic approach for treating IHD.
Collapse
Affiliation(s)
- Hugang Jiang
- Department of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Yan Tang
- Department of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Ai Liu
- Department of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Chunzhen Ren
- Department of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Wenyan Lin
- Daytime Diagnosis and Treatment Center, Gansu Provincial People’s Hospital, Lanzhou, Gansu, China
| | - Kai Liu
- Department of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Xinke Zhao
- Cardiovascular Clinical Medical Center, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Yingdong Li
- Department of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| |
Collapse
|
|
4
|
Borges LF, Manetti M. Telocytes and Stem Cells. RESIDENT STEM CELLS AND REGENERATIVE THERAPY 2024:305-337. [DOI: 10.1016/b978-0-443-15289-4.00011-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
5
|
Babadag S, Çelebi-Saltik B. A cellular regulator of the niche: telocyte. Tissue Barriers 2023; 11:2131955. [PMID: 36218299 PMCID: PMC10606812 DOI: 10.1080/21688370.2022.2131955] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 09/24/2022] [Accepted: 09/28/2022] [Indexed: 10/17/2022] Open
Abstract
Interstitial cells are present in the environment of stem cells in order to increase stem cell proliferation and differentiation and they are important to increase the efficiency of their transplantation. Telocytes (TCs) play an important role both in the preservation of tissue organ integrity and in the pathophysiology of many diseases, especially cancer. They make homo- or heterocellular contacts to form the structure of 3D network through their telopodes and deliver signaling molecules via a juxtacrine and/or paracrine association by budding shed vesicles into the vascular, nervous and endocrine systems. During this interaction, along with organelles, mRNA, microRNA, long non-coding RNA, and genomic DNA are transferred. This review article not only specifies the properties of TCs and their roles in the tissue organ microenvironment but also gives information about the factors that play a role in the transport of epigenetic information by TCs.
Collapse
Affiliation(s)
- Sena Babadag
- Department of Stem Cell Sciences, Hacettepe University Graduate School of Health Sciences, Sihhiye, Turkey
- Center for Stem Cell Research and Development, Hacettepe University, Sihhiye, Turkey
| | - Betül Çelebi-Saltik
- Department of Stem Cell Sciences, Hacettepe University Graduate School of Health Sciences, Sihhiye, Turkey
- Center for Stem Cell Research and Development, Hacettepe University, Sihhiye, Turkey
| |
Collapse
|
|
6
|
Zhang X, Lu P, Shen X. Morphologies and potential roles of telocytes in nervous tissue. CLINICAL AND TRANSLATIONAL DISCOVERY 2023; 3. [DOI: 10.1002/ctd2.186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 03/16/2023] [Indexed: 01/03/2025]
Abstract
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.
Collapse
Affiliation(s)
- Xu Zhang
- Institute for Reproductive Health Shanghai Institute for Biomedical and Pharmaceutical Technologies Shanghai China
| | - Ping Lu
- Institute for Reproductive Health Shanghai Institute for Biomedical and Pharmaceutical Technologies Shanghai China
| | - Xiaorong Shen
- Institute for Reproductive Health Shanghai Institute for Biomedical and Pharmaceutical Technologies Shanghai China
| |
Collapse
|
|
7
|
Wei XJ, Chen TQ, Yang XJ. Telocytes in Fibrosis Diseases: From Current Findings to Future Clinical Perspectives. Cell Transplant 2022; 31:9636897221105252. [PMID: 35748420 PMCID: PMC9235300 DOI: 10.1177/09636897221105252] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/11/2022] [Indexed: 11/17/2022] Open
Abstract
Telocytes (TCs), a distinct type of interstitial (stromal) cells, have been discovered in many organs of human and mammal animals. TCs, which have unique morphological characteristics and abundant paracrine substance, construct a three-dimensional (3D) interstitial network within the stromal compartment by homocellular and heterocellular communications which are important for tissue homeostasis and normal development. Fibrosis-related diseases remain a common but challenging problem in the field of medicine with unclear pathogenesis and limited therapeutic options. Recently, increasing evidences suggest that where TCs are morphologically or numerically destructed, many diseases continuously develop, finally lead to irreversible interstitial fibrosis. It is not difficult to find that TCs are associated with chronic inflammation and fibrosis. This review mainly discusses relationship between TCs and the occurrence of fibrosis in various diseases. We analyzed in detail the potential roles and speculated mechanisms of TCs in onset and progression of systemic fibrosis diseases, as well as providing the most up-to-date research on the current therapeutic roles of TCs and involved related pathways. Only through continuous research and exploration in the future can we uncover its magic veil and provide strategies for treatment of fibrosis-related disease.
Collapse
Affiliation(s)
- Xiao-jiao Wei
- Department of Obstetrics and
Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, P.R.
China
| | - Tian-quan Chen
- Department of Obstetrics and
Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, P.R.
China
| | - Xiao-jun Yang
- Department of Obstetrics and
Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, P.R.
China
| |
Collapse
|
|
8
|
Condrat CE, Barbu MG, Thompson DC, Dănilă CA, Boboc AE, Suciu N, Crețoiu D, Voinea SC. Roles and distribution of telocytes in tissue organization in health and disease. TISSUE BARRIERS IN DISEASE, INJURY AND REGENERATION 2021:1-41. [DOI: 10.1016/b978-0-12-818561-2.00001-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
9
|
Cretoiu D, Roatesi S, Bica I, Plesca C, Stefan A, Bajenaru O, Condrat CE, Cretoiu SM. Simulation and Modeling of Telocytes Behavior in Signaling and Intercellular Communication Processes. Int J Mol Sci 2020; 21:ijms21072615. [PMID: 32283771 PMCID: PMC7177713 DOI: 10.3390/ijms21072615] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 04/06/2020] [Accepted: 04/07/2020] [Indexed: 02/07/2023] Open
Abstract
Background: Telocytes (TCs) are unique interstitial or stromal cells of mesodermal origin, defined by long cellular extensions called telopodes (Tps) which form a network, connecting them to surrounding cells. TCs were previously found around stem and progenitor cells, and were thought to be most likely involved in local tissue metabolic equilibrium and regeneration. The roles of telocytes are still under scientific scrutiny, with existing studies suggesting they possess various functions depending on their location. Methods: Human myometrium biopsies were collected from pregnant and non-pregnant women, telocytes were then investigated in myometrial interstitial cell cultures based on morphological criteria and later prepared for time-lapse microscopy. Semi-analytical and numerical solutions were developed to highlight the geometric characteristics and the behavior of telocytes. Results: Results were gathered in a database which would further allow efficient telocyte tracking and indexing in a content-based image retrieval (CBIR) of digital medical images. Mathematical analysis revealed pivotal information regarding the homogeneity, hardness and resistance of telocytes’ structure. Cellular activity models were monitored in vitro, therefore supporting the creation of databases of telocyte images. Conclusions: The obtained images were analyzed, using segmentation techniques and mathematical models in conjunction with computer simulation, in order to depict TCs behavior in relation to surrounding cells. This paper brings an important contribution to the development of bioinformatics systems by creating software-based telocyte models that could be used both for diagnostic and educational purposes.
Collapse
Affiliation(s)
- Dragos Cretoiu
- Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (D.C.); (S.M.C.)
- Alessandrescu-Rusescu National Institute of Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania;
| | - Simona Roatesi
- Department of Applied Informatics, Faculty of Information Systems and Cyber Security, “Ferdinand I” Military Technical Academy, 050141 Bucharest, Romania;
- Correspondence:
| | - Ion Bica
- Department of Computers and Cyber Security, Faculty of Information Systems and Cyber Security, “Ferdinand I” Military Technical Academy, 050141 Bucharest, Romania;
| | - Cezar Plesca
- Department of Applied Informatics, Faculty of Information Systems and Cyber Security, “Ferdinand I” Military Technical Academy, 050141 Bucharest, Romania;
| | - Amado Stefan
- Department of Integrated Systems of Aviation and Mechanics, Faculty of Aircraft and Military Vehicles, Technical Military Academy “Ferdinand I”, 050141 Bucharest, Romania;
| | | | - Carmen Elena Condrat
- Alessandrescu-Rusescu National Institute of Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania;
| | - Sanda Maria Cretoiu
- Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (D.C.); (S.M.C.)
| |
Collapse
|
|
10
|
Mitrofanova L, Hazratov A, Galkovsky B, Gorshkov A, Bobkov D, Gulyaev D, Shlyakhto E. Morphological and immunophenotypic characterization of perivascular interstitial cells in human glioma: Telocytes, pericytes, and mixed immunophenotypes. Oncotarget 2020; 11:322-346. [PMID: 32064038 PMCID: PMC6996916 DOI: 10.18632/oncotarget.27340] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 10/26/2019] [Indexed: 12/12/2022] Open
Abstract
Telocytes (Tcs) and pericytes (Pcs) are two types of perivascular interstitial cell known to be widespread in various organs and tissues, including the brain. We postulated that Tcs and Pcs may be involved in glioblastoma (GBM) neovascularization.
Collapse
Affiliation(s)
- Lubov Mitrofanova
- Almazov National Medical Research Centre, Pathomorphology Research Laboratory, St. Petersburg, Russia
| | - Anton Hazratov
- Almazov National Medical Research Centre, Pathomorphology Research Laboratory, St. Petersburg, Russia
| | - Boris Galkovsky
- Almazov National Medical Research Centre, Pathomorphology Research Laboratory, St. Petersburg, Russia
| | - Andrey Gorshkov
- Almazov National Medical Research Centre, Pathomorphology Research Laboratory, St. Petersburg, Russia.,Smorodintsev Research Institute of Influenza, Laboratory of Intracellular Signaling and Transport, St. Petersburg, Russia
| | - Danila Bobkov
- Smorodintsev Research Institute of Influenza, Laboratory of Intracellular Signaling and Transport, St. Petersburg, Russia.,Institute of Cytology of the Russian Academy of Science, Laboratory of Cell Biology in Culture, St. Petersburg, Russia
| | - Dmitry Gulyaev
- Almazov National Medical Research Centre, Research Department of Neurosurgery, St. Petersburg, Russia
| | - Evgeny Shlyakhto
- Almazov National Medical Research Centre, General Director, St. Petersburg, Russia
| |
Collapse
|
|
11
|
Zhou Y, Yang Y, Liang T, Hu Y, Tang H, Song D, Fang H. The regulatory effect of microRNA-21a-3p on the promotion of telocyte angiogenesis mediated by PI3K (p110α)/AKT/mTOR in LPS induced mice ARDS. J Transl Med 2019; 17:427. [PMID: 31878977 PMCID: PMC6933909 DOI: 10.1186/s12967-019-02168-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 12/04/2019] [Indexed: 02/07/2023] Open
Abstract
Background Telocytes (TCs) are newly identified interstitial cells that participate in tissue protection and repair. The present study investigated the mechanisms underlying the protective effect of TCs in a mouse model of respiratory distress. Methods The mouse model of acute respiratory distress syndrome (ARDS) was established by intratracheal instillation of lipopolysaccharide (LPS). After instillation of TCs culture medium, lung injury was assessed, and angiogenesis markers, including CD31 and endothelial nitric oxide synthase (eNOS), were detected by immunofluorescence. Bioinformatics analysis was used to screen significantly differentially expressed microRNAs (miRNAs) in cultured TCs stimulated with LPS, and the regulation of downstream angiogenesis genes by these miRNAs was analysed and verified. PI3K subunits and pathways were evaluated by using a PI3K p110α inhibitor to study the involved mechanisms. Results In ARDS mice, instillation of TCs culture medium ameliorated LPS-induced inflammation and lung injury and increased the protein levels of CD31 and eNOS in the injured lungs. A total of 7 miRNAs and 1899 mRNAs were differentially regulated in TCs stimulated with LPS. Functional prediction analysis showed that the differentially expressed mRNAs were enriched in angiogenesis-related processes, which were highly correlated with miR-21a-3p. Culture medium from TCs with miR-21a-3p inhibition failed to promote angiogenesis in mouse models of LPS-induced ARDS. In cultured TCs, LPS stimulation upregulated the expression of miR-21a-3p, which further targeted the transcription factor E2F8 and decreased Notch2 protein expression. TCs culture medium enhanced hemangioendothelioma endothelial cells (EOMA cells) proliferation, which was blocked by the miR-21a-3p inhibitor. The PI3K p110α inhibitor decreased vascular endothelial growth factor levels in LPS-stimulated TCs and reversed the enhancing effect of TCs culture medium on EOMA cells proliferation. Conclusions TCs exerted protective effects under inflammatory conditions by promoting angiogenesis via miR-21a-3p. The PI3K p110α subunit and transcriptional factor E2F8 could be involved in this process.
Collapse
Affiliation(s)
- Yile Zhou
- Department of Anaesthesiology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201508, People's Republic of China
| | - Yajie Yang
- Department of Anaesthesiology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201508, People's Republic of China
| | - Tao Liang
- Department of Anaesthesiology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201508, People's Republic of China
| | - Yan Hu
- Department of Anaesthesiology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201508, People's Republic of China.,Department of Anaesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China
| | - Haihong Tang
- Department of Anaesthesiology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201508, People's Republic of China
| | - Dongli Song
- Zhongshan Hospital Institute for Clinical Science, Shanghai Institute of Clinical Bioinformatics, Shanghai Engineering Research for AI Technology for Cardiopulmonary Diseases, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Hao Fang
- Department of Anaesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China. .,Department of Anaesthesiology, Minhang Branch, Zhongshan Hospital, Fudan University, 170 Xinsong Road, Shanghai, 201199, People's Republic of China.
| |
Collapse
|
|
12
|
Awad M, Gaber W, Ibrahim D. Onset of Appearance and Potential Significance of Telocytes in the Developing Fetal Lung. MICROSCOPY AND MICROANALYSIS : THE OFFICIAL JOURNAL OF MICROSCOPY SOCIETY OF AMERICA, MICROBEAM ANALYSIS SOCIETY, MICROSCOPICAL SOCIETY OF CANADA 2019; 25:1246-1256. [PMID: 31524125 DOI: 10.1017/s1431927619014922] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
CD34, vimentin, and vascular endothelial growth factor immunohistochemical analysis and electron microscopic tools were employed to record the initial appearance of telocytes (TCs) and stage-by-stage variations in TC localizations in the developing rabbit lung. TCs could not be identified in the primitive embryonic lung until day 18 of gestation. In the pseudoglandular lung, CD34+ TCs had been recorded under the cartilage of the main bronchus, in the wall of large-sized pulmonary vessels and large epithelial tubes. In the canalicular phase, TCs could be demonstrated in the smooth muscle layer of the bronchioles including the terminal ones. The strength of CD34 immunoreactive signals had been amplified by age until the day of parturition. Ultrastructurally, TCs consisted of a tiny body and exceptionally long telopodes (Tps). The Tp consisted of alternating thin segments (podomers) and dilated ones (podoms). The Tp sometimes branched with a dichotomous pattern. TCs interconnected in a network either by homocellular junctions with neighboring TCs or by heterocellular junctions with smooth muscle cells and alveolar cells. Collectively, early detection of TCs in pulmonary vessels suggests a potential role for TCs in their angiogenesis. For the lung tissue, TCs seem to be involved in the regulation of lung histogenesis.
Collapse
Affiliation(s)
- Mahmoud Awad
- Department of Histology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt
| | - Wafaa Gaber
- Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, Assuit University, Assuit, Egypt
| | - Dalia Ibrahim
- Department of Histology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt
| |
Collapse
|
|
13
|
Rusu MC, Hostiuc S, Fildan AP, Tofolean DE. Critical Review: What Cell Types Are the Lung Telocytes? Anat Rec (Hoboken) 2019; 303:1280-1292. [PMID: 31443120 DOI: 10.1002/ar.24237] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Revised: 03/11/2019] [Accepted: 05/13/2019] [Indexed: 12/15/2022]
Abstract
Telocytes (TCs) are stromal cells defined by peculiar long, thin, moniliform prolongations known as telopodes. When isolated, their morphology often lacks the specificity for the proper definition of a particular cell type. Recent studies have linked TCs with different functions and different cell lineages. Although some authors have studied pulmonary TCs, their research has important limitations that we will attempt to summarize in this article. We will focus our analysis on the following: the culture methods used to study them, the lack of proper discrimination of TCs from lymphatic endothelial cells (LECs), whose ultrastructures are very similar, and the immune phenotype of TCs, which may appear in other cell types such as those related to the endothelial lineage or stem/progenitor cells. In conclusion, the cellular diagnosis of lung TCs should be considered with caution until properly designed studies can positively identify these cells and differentiate them from other cell types such as LECs and stem/progenitor cells. Anat Rec, 303:1280-1292, 2020. © 2019 American Association for Anatomy.
Collapse
Affiliation(s)
- Mugurel C Rusu
- Division of Anatomy, Faculty of Dental Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Sorin Hostiuc
- Department of Legal Medicine and Bioethics, Faculty of Dental Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Ariadna P Fildan
- Internal Medicine Department, Faculty of Medicine, Ovidius University of Constanţa, Constatnţa, Romania
| | - Doina E Tofolean
- Internal Medicine Department, Faculty of Medicine, Ovidius University of Constanţa, Constatnţa, Romania
| |
Collapse
|
|
14
|
Varga I, Polák Š, Kyselovič J, Kachlík D, Danišovič Ľ, Klein M. Recently Discovered Interstitial Cell Population of Telocytes: Distinguishing Facts from Fiction Regarding Their Role in the Pathogenesis of Diverse Diseases Called "Telocytopathies". MEDICINA (KAUNAS, LITHUANIA) 2019; 55:E56. [PMID: 30781716 PMCID: PMC6410178 DOI: 10.3390/medicina55020056] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 01/14/2019] [Accepted: 02/11/2019] [Indexed: 12/19/2022]
Abstract
In recent years, the interstitial cells telocytes, formerly known as interstitial Cajal-like cells, have been described in almost all organs of the human body. Although telocytes were previously thought to be localized predominantly in the organs of the digestive system, as of 2018 they have also been described in the lymphoid tissue, skin, respiratory system, urinary system, meninges and the organs of the male and female genital tracts. Since the time of eminent German pathologist Rudolf Virchow, we have known that many pathological processes originate directly from cellular changes. Even though telocytes are not widely accepted by all scientists as an individual and morphologically and functionally distinct cell population, several articles regarding telocytes have already been published in such prestigious journals as Nature and Annals of the New York Academy of Sciences. The telocyte diversity extends beyond their morphology and functions, as they have a potential role in the etiopathogenesis of different diseases. The most commonly described telocyte-associated diseases (which may be best termed "telocytopathies" in the future) are summarized in this critical review. It is difficult to imagine that a single cell population could be involved in the pathogenesis of such a wide spectrum of pathological conditions as extragastrointestinal stromal tumors ("telocytomas"), liver fibrosis, preeclampsia during pregnancy, tubal infertility, heart failure and psoriasis. In any case, future functional studies of telocytes in vivo will help to understand the mechanism by which telocytes contribute to tissue homeostasis in health and disease.
Collapse
Affiliation(s)
- Ivan Varga
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, 813 72 Bratislava, Slovakia.
| | - Štefan Polák
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, 813 72 Bratislava, Slovakia.
| | - Ján Kyselovič
- Fifth Department of Internal Medicine, Faculty of Medicine, Comenius University in Bratislava, 813 72 Bratislava, Slovakia.
| | - David Kachlík
- Institute of Anatomy, Second Faculty of Medicine, Charles University, 128 00 Prague, Czech Republic.
| | - Ľuboš Danišovič
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, 813 72 Bratislava, Slovakia.
| | - Martin Klein
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, 813 72 Bratislava, Slovakia.
| |
Collapse
|
|
15
|
Ma R, Wu P, Shi Q, Song D, Fang H. Telocytes promote VEGF expression and alleviate ventilator-induced lung injury in mice. Acta Biochim Biophys Sin (Shanghai) 2018; 50:817-825. [PMID: 29924305 DOI: 10.1093/abbs/gmy066] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Indexed: 01/17/2023] Open
Abstract
Mechanical ventilation (MV) is an important procedure for the treatment of patients with acute lung injury or acute respiratory distress syndrome in a clinical setting; however, MV can lead to severe complications, including ventilator-induced lung injury (VILI). Telocytes (TCs) can promote tissue repair following injury in the heart, kidneys, and other organs. The aim of this study was to investigate the role of TCs in VILI in mice and the associated mechanisms. By using in vivo studies in mice and in vitro studies in cells, we demonstrated that an airway injection of TCs can reduce the pulmonary inflammatory response and improve the lung function in mice with VILI and promote the proliferation of pulmonary vascular endothelial cells. We also demonstrated that the impact of TCs on VILI repair might partially due to vascular endothelial growth factor (VEGF) secreted by TCs upon VILI stimulation, and that VEGF could induce the proliferation of hemangioendothelioma endothelial cells (EOMA). Collectively, our results revealed novel functions of TCs in VILA repair and shed light on the complications that are caused by MV.
Collapse
Affiliation(s)
- Ruihua Ma
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Pinwen Wu
- Department of Anesthesiology, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qiqing Shi
- Department of Anesthesiology, Children's Hospital of Fudan University, Shanghai, China
| | - Dongli Song
- Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hao Fang
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Anesthesiology, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai, China
| |
Collapse
|
|
16
|
Zani BC, Sanches BDA, Maldarine JS, Biancardi MF, Santos FCA, Barquilha CN, Zucão MI, Baraldi CMB, Felisbino SL, Góes RM, Vilamaior PSL, Taboga SR. Telocytes role during the postnatal development of the Mongolian gerbil jejunum. Exp Mol Pathol 2018; 105:130-138. [PMID: 30003874 DOI: 10.1016/j.yexmp.2018.07.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Revised: 06/26/2018] [Accepted: 07/07/2018] [Indexed: 01/29/2023]
Abstract
Telocytes are recently categorised CD34-positive interstitial cells that comprise the cells which were previously called interstitial Cajal-like cells (ICLCs). These were detected in the stroma of various organs such as the prostate, lungs, mammary glands, liver, gallbladder, and jejunum, among others. Several functions have been proposed for telocytes, such as a supportive role in smooth muscle contraction and immune function in adult organs, and tissue organisation and paracrine signalling during development, as well as others. In the jejunum, little is known about the function of telocytes in the adult organ, or is there any information about when these cells develop or if they could have an auxiliary role in the development of the jejunum. The present study employed histological, immunohistochemical and immunofluorescence techniques on histological sections of the jejunum of Mongolian gerbil pups on two different days of postnatal development of the jejunum, covering the maturation period of the organ. By immunolabelling for CD34, it was observed that telocytes are already present in the jejunum during the first week of postnatal life and exist in close association with the developing muscularis mucosae, which are therefore TGFβ1-positive. The telocytes are still present at the end of the first month of life, and a portion of them present co-localisation with c-Kit. Fibroblast-like cells, which are exclusively c-Kit-positive, are also observed, which may indicate the presence of interstitial Cajal cells (ICCs). Finally, it can be hypothesised that a portion of the telocytes may give rise to ICCs, which are c-Kit-positive but CD34 negative.
Collapse
Affiliation(s)
- Bruno C Zani
- Univ. Estadual Paulista - UNESP, Department of Biology, Laboratory of Microscopy and Microanalysis, Cristóvão Colombo St., 2265, São José do Rio Preto, São Paulo, Brazil
| | - Bruno D A Sanches
- Department of Structural and Functional Biology, State University of Campinas, Bertrand Russel Av., Campinas, São Paulo, Brazil
| | - Juliana S Maldarine
- Department of Structural and Functional Biology, State University of Campinas, Bertrand Russel Av., Campinas, São Paulo, Brazil
| | - Manoel F Biancardi
- Department of Histology, Embryology and Cell Biology, Federal University of Goiás, Samambaia II, Goiânia, Goiás 74001970, Brazil
| | - Fernanda C A Santos
- Department of Histology, Embryology and Cell Biology, Federal University of Goiás, Samambaia II, Goiânia, Goiás 74001970, Brazil
| | - Caroline N Barquilha
- Univ. Estadual Paulista - UNESP, Institute of Biosciences, Prof. Dr. Antônio Celso Wagner Zanin St., 250, Rubião Júnior District, Botucatu, São Paulo 18618-689, Brazil
| | - Mariele I Zucão
- Univ. Estadual Paulista - UNESP, Department of Biology, Laboratory of Microscopy and Microanalysis, Cristóvão Colombo St., 2265, São José do Rio Preto, São Paulo, Brazil
| | - Carolina M B Baraldi
- Univ. Estadual Paulista - UNESP, Department of Biology, Laboratory of Microscopy and Microanalysis, Cristóvão Colombo St., 2265, São José do Rio Preto, São Paulo, Brazil
| | - Sergio L Felisbino
- Univ. Estadual Paulista - UNESP, Department of Biology, Laboratory of Microscopy and Microanalysis, Cristóvão Colombo St., 2265, São José do Rio Preto, São Paulo, Brazil; Univ. Estadual Paulista - UNESP, Institute of Biosciences, Prof. Dr. Antônio Celso Wagner Zanin St., 250, Rubião Júnior District, Botucatu, São Paulo 18618-689, Brazil
| | - Rejane M Góes
- Univ. Estadual Paulista - UNESP, Department of Biology, Laboratory of Microscopy and Microanalysis, Cristóvão Colombo St., 2265, São José do Rio Preto, São Paulo, Brazil; Department of Structural and Functional Biology, State University of Campinas, Bertrand Russel Av., Campinas, São Paulo, Brazil
| | - Patricia S L Vilamaior
- Univ. Estadual Paulista - UNESP, Department of Biology, Laboratory of Microscopy and Microanalysis, Cristóvão Colombo St., 2265, São José do Rio Preto, São Paulo, Brazil
| | - Sebastião R Taboga
- Univ. Estadual Paulista - UNESP, Department of Biology, Laboratory of Microscopy and Microanalysis, Cristóvão Colombo St., 2265, São José do Rio Preto, São Paulo, Brazil; Department of Structural and Functional Biology, State University of Campinas, Bertrand Russel Av., Campinas, São Paulo, Brazil.
| |
Collapse
|
|
17
|
Tan HW, Xu YM, Wu DD, Lau ATY. Recent insights into human bronchial proteomics - how are we progressing and what is next? Expert Rev Proteomics 2018; 15:113-130. [PMID: 29260600 DOI: 10.1080/14789450.2017.1417847] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The human respiratory system is highly prone to diseases and complications. Many lung diseases, including lung cancer (LC), tuberculosis (TB), and chronic obstructive pulmonary disease (COPD) have been among the most common causes of death worldwide. Cystic fibrosis (CF), the most common genetic disease in Caucasians, has adverse impacts on the lungs. Bronchial proteomics plays a significant role in understanding the underlying mechanisms and pathogenicity of lung diseases and provides insights for biomarker and therapeutic target discoveries. Areas covered: We overview the recent achievements and discoveries in human bronchial proteomics by outlining how some of the different proteomic techniques/strategies are developed and applied in LC, TB, COPD, and CF. Also, the future roles of bronchial proteomics in predictive proteomics and precision medicine are discussed. Expert commentary: Much progress has been made in bronchial proteomics. Owing to the advances in proteomics, we now have better ability to isolate proteins from desired cellular compartments, greater protein separation methods, more powerful protein detection technologies, and more sophisticated bioinformatic techniques. These all contributed to our further understanding of lung diseases and for biomarker and therapeutic target discoveries.
Collapse
Affiliation(s)
- Heng Wee Tan
- a Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics , Shantou University Medical College , Shantou , People's Republic of China
| | - Yan-Ming Xu
- a Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics , Shantou University Medical College , Shantou , People's Republic of China
| | - Dan-Dan Wu
- a Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics , Shantou University Medical College , Shantou , People's Republic of China
| | - Andy T Y Lau
- a Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics , Shantou University Medical College , Shantou , People's Republic of China
| |
Collapse
|
|
18
|
Sanches BDA, Maldarine JS, Zani BC, Tamarindo GH, Biancardi MF, Santos FCA, Rahal P, Góes RM, Felisbino SL, Vilamaior PSL, Taboga SR. Telocytes play a key role in prostate tissue organisation during the gland morphogenesis. J Cell Mol Med 2017; 21:3309-3321. [PMID: 28840644 PMCID: PMC5706570 DOI: 10.1111/jcmm.13234] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 04/15/2017] [Indexed: 01/19/2023] Open
Abstract
Telocytes are CD34-positive interstitial cells, known to exert several functions, one of which is a role in tissue organisation, previously demonstrated by telocytes in the myocardium. The existence of telocytes in the prostate has recently been reported, however, there is a lack of information regarding the function of these cells in prostate tissue, and information regarding the possible role of these cells in prostatic development. This study used immunofluorescence techniques in prostate tissue and prostatic telocytes in culture to determine the relationship between telocytes and prostate morphogenesis. Furthermore, immunofluorescent labelling of telocytes was performed on prostate tissue at different stages of early postnatal development. Initially, CD34-positive cells are found at the periphery of the developing alveoli, later in the same region, c-kit-positive cells and cells positive for both factors are verified and CD34-positive cells were predominantly observed in the interalveolar stroma and the region surrounding the periductal smooth muscle. Fluorescence assays also demonstrated that telocytes secrete TGF-β1 and are ER-Beta (ERβ) positive. The results suggest that telocytes play a changing role during development, initially supporting the differentiation of periductal and perialveolar smooth muscle, and later, producing dense networks that separate alveoli groups and form a barrier between the interalveolar region and periurethral smooth muscle. We conclude that telocytes play a relevant role in prostate tissue organisation during postnatal development.
Collapse
Affiliation(s)
- Bruno D A Sanches
- Department of Structural and Functional Biology, State University of Campinas, Campinas, São Paulo, Brazil
| | - Juliana S Maldarine
- Department of Biology, Univ. Estadual Paulista (UNESP), São José do Rio Preto, São Paulo, Brazil
| | - Bruno C Zani
- Department of Biology, Univ. Estadual Paulista (UNESP), São José do Rio Preto, São Paulo, Brazil
| | - Guilherme H Tamarindo
- Department of Structural and Functional Biology, State University of Campinas, Campinas, São Paulo, Brazil
| | - Manoel F Biancardi
- Department of Histology, Embryology and Cell Biology, Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Fernanda C A Santos
- Department of Histology, Embryology and Cell Biology, Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Paula Rahal
- Department of Biology, Univ. Estadual Paulista (UNESP), São José do Rio Preto, São Paulo, Brazil
| | - Rejane M Góes
- Department of Biology, Univ. Estadual Paulista (UNESP), São José do Rio Preto, São Paulo, Brazil
| | - Sérgio L Felisbino
- Department of Morphology, Institute of Biology (IB), Univ. Estadual Paulista - UNESP, Botucatu, São Paulo, Brazil
| | - Patricia S L Vilamaior
- Department of Biology, Univ. Estadual Paulista (UNESP), São José do Rio Preto, São Paulo, Brazil
| | - Sebastião R Taboga
- Department of Biology, Univ. Estadual Paulista (UNESP), São José do Rio Preto, São Paulo, Brazil
| |
Collapse
|
|
19
|
Ibba-Manneschi L, Rosa I, Manetti M. Telocytes in Chronic Inflammatory and Fibrotic Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 913:51-76. [PMID: 27796880 DOI: 10.1007/978-981-10-1061-3_4] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Telocytes are a peculiar stromal (interstitial) cell type implicated in tissue homeostasis and development, as well as in the pathophysiology of several disorders. Severe damage and reduction of telocytes have been reported during fibrotic remodeling of multiple organs in various diseases, including scleroderma, Crohn's disease, ulcerative colitis, and liver fibrosis, as well as in chronic inflammatory lesions like those of primary Sjögren's syndrome and psoriasis. Owing to their close relationship with stem cells, telocytes are also supposed to contribute to tissue repair/regeneration. Indeed, telocytes are universally considered as "connecting cells" mostly oriented to intercellular signaling. On the basis of recent promising experimental findings, in the near future, telocyte transplantation might represent a novel therapeutic opportunity to control the evolution of chronic inflammatory and fibrotic diseases. Notably, there is evidence to support that telocytes could help in preventing abnormal activation of immune cells and fibroblasts, as well as in attenuating the altered matrix organization during the fibrotic process. By targeting telocytes alone or in tandem with stem cells, we might be able to promote regeneration and prevent the evolution to irreversible tissue injury. Besides exogenous transplantation, exploring pharmacological or non-pharmacological methods to enhance the growth and/or survival of telocytes could be an additional therapeutic strategy for many disorders.
Collapse
Affiliation(s)
- Lidia Ibba-Manneschi
- Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, Florence, 50134, Italy
| | - Irene Rosa
- Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, Florence, 50134, Italy
| | - Mirko Manetti
- Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, Florence, 50134, Italy.
| |
Collapse
|
|
20
|
Abstract
Telocyte (TC) is a new identified interstitial cell type with a small nuclear and one or several long and thin prolongations with enlargements on them. They were found in many mammals including humans, mouse, rats, dogs, and monkeys and play vital roles in many physiological and pathological conditions. The ultrastructure of mitochondria was observed in TCs, and the alterations were found in TCs from inflammatory ureter tissue. MtDNA is associated with mitochondria normal functions and involved in physiological and pathological processes. However, mitochondria and mtDNA in TCs were not investigated deeply. This review will introduce the origin, distribution, morphology, and functions of TCs and the distribution and functions of TC mitochondria in order to improve a better understanding of the potential functions of mtDNA in TCs.
Collapse
|
|
21
|
Zhang B, Yang C, Qiao L, Li Q, Wang C, Yan X, Lin J. Telocytes: a potential defender in the spleen of Npc1 mutant mice. J Cell Mol Med 2016; 21:848-859. [PMID: 27860245 PMCID: PMC5387173 DOI: 10.1111/jcmm.13024] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Accepted: 10/02/2016] [Indexed: 12/30/2022] Open
Abstract
Niemann–Pick disease, type C1 (Npc1), is an atypical lysosomal storage disorder caused by autosomal recessive inheritance of mutations in Npc1 gene. In the Npc1 mutant mice (Npc1−/−), the initial manifestation is enlarged spleen, concomitant with free cholesterol accumulation. Telocytes (TCs), a novel type of interstitial cell, exist in a variety of tissues including spleen, presumably thought to be involved in many biological processes such as nursing stem cells and recruiting inflammatory cells. In this study, we found that the spleen is significantly enlarged in Npc1−/− mice, and the results from transmission electron microscopy examination and immunostaining using three different TCs markers, c‐Kit, CD34 and Vimentin revealed significantly increased splenic TCs in Npc1−/− mice. Furthermore, hematopoietic stem cells and macrophages were also elevated in Npc1−/− spleen. Taken together, our data indicate that splenic TCs might alleviate the progress of splenic malfunction via recruiting hematopoietic stem cells and macrophages.
Collapse
Affiliation(s)
- Bichao Zhang
- College of Life Science and Technology, Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China
| | - Ciqing Yang
- College of Life Science and Technology, Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China
| | - Liang Qiao
- College of Life Science and Technology, Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China
| | - Qiuling Li
- College of Life Science and Technology, Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China
| | - Congrui Wang
- College of Life Science and Technology, Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China
| | - Xin Yan
- College of Life Science and Technology, Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China
| | - Juntang Lin
- College of Life Science and Technology, Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China.,College of Biomedical Engineering, Stem Cell and Biotherapy Engineering Research Center of Henan, Xinxiang Medical University, Xinxiang, China.,Institute of Anatomy I, University of Jena School of Medicine, Jena University Hospital, Jena, Germany
| |
Collapse
|
|
22
|
Yang P, Zhu X, Wang L, Ahmed N, Huang Y, Chen H, Zhang Q, Ullah S, Liu T, Guo D, Brohi SA, Chen Q. Cellular Evidence of Telocytes as Novel Interstitial Cells Within the Magnum of Chicken Oviduct. Cell Transplant 2016; 26:135-143. [PMID: 27590447 DOI: 10.3727/096368916x692942] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Telocytes are a novel type of interstitial cell that has been identified in many organs of mammals, but there is little information available on these cells in avian species. This study shows the latest findings associated with telocytes in the muscular layer and lamina propria of the magnum of chicken oviduct analyzed by transmission electron microscopy. Telocytes are characterized by telopodes, which are thin and long prolongations, and a small amount of cytoplasm rich with mitochondria. Spindle- or triangular-shaped telocytes were detected at various locations in the magnum. In the muscular layer, telocytes have direct connection with smooth muscle cells. The cell body of telocytes along with their long telopodes mainly exists in the interstitial space between the smooth muscle bundles, whereas large numbers of short telopodes are scattered in between the smooth muscle cells. In the lamina propria, extremely long telopodes are twisting around each other and are usually collagen embedded. Both in the lamina propria and muscular layer, telocytes have a close relationship with other cell types, such as immune cells and blood vessels. Telopodes appear with dichotomous branching alternating between the podom and podomer, forming a 3D network structure with complex homo- and heterocellular junctions. In addition, a distinctive size of the vesicles is visible around the telopodes and may be released from telopodes because of the close relation between the vesicle and telopode. All characteristics of telocytes in the magnum indicate that telocytes may play a potential, but important, role in the pathogenesis of oviduct diseases.
Collapse
|
|
23
|
Arafat EA. Ultrastructural and immunohistochemical characteristics of telocytes in the skin and skeletal muscle of newborn rats. Acta Histochem 2016; 118:574-580. [PMID: 27344553 DOI: 10.1016/j.acthis.2016.06.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Revised: 05/29/2016] [Accepted: 06/06/2016] [Indexed: 02/06/2023]
Abstract
Telocytes (TCs) are newly described interstitial cells that might play a role in normal and pathological conditions. The aim of this study was designed to investigate its existence in the skin and skeletal muscle of one day old newborn rats and to study their ultrastructure and immunohistochemical characteristics. Ten rats (one day old newborn) were used in this study. Dorsal skin and femoral skeletal muscle samples were obtained and examined by CD117, CD34, semi-thin and ultrathin sections examination. Semi-thin sections examination revealed multiple spindle shape cells with cytoplasmic extension in the skin and in between muscle fibers. Telocytes showed positive reaction for both CD117 and CD34 immunostains. By electron microscopy these cells were spindle shaped with small cell bodies and long processes. Telocytes showed homo-cellular junctions between two adjacent telocytes and hetero-cellular junctions between telocytes and other cellular and non-cellular structures. Multiple vesicles were seen either intra-cellular or budding from the cell membrane or detached from the telocytes leaving caveolae. It could be concluded that telocytes are present in the skin and skeletal muscle of one day old newborn rats. They might play a role in pathologies and regenerative medicine due to their ability to release vesicles.
Collapse
|
|
24
|
Kostin S. Cardiac telocytes in normal and diseased hearts. Semin Cell Dev Biol 2016; 55:22-30. [PMID: 26912117 DOI: 10.1016/j.semcdb.2016.02.023] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Accepted: 02/16/2016] [Indexed: 12/28/2022]
|
|
25
|
Li YY, Lu SS, Xu T, Zhang HQ, Li H. Comparative Analysis of Telomerase Activity in CD117⁺ CD34⁺ Cardiac Telocytes with Bone Mesenchymal Stem Cells, Cardiac Fibroblasts and Cardiomyocytes. Chin Med J (Engl) 2016; 128:1942-7. [PMID: 26168836 PMCID: PMC4717931 DOI: 10.4103/0366-6999.160560] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background: This study characterized the cardiac telocyte (TC) population both in vivo and in vitro, and investigated its telomerase activity related to mitosis. Methods: Using transmission electron microscopy and a phase contrast microscope, the typical morphological features of cardiac TCs were observed; by targeting the cell surface proteins CD117 and CD34, CD117+CD34+ cardiac TCs were sorted via flow cytometry and validated by immunofluorescence based on the primary cell culture. Then the optimized basal nutrient medium for selected population was examined with the cell counting kit 8. Under this conditioned medium, the process of cell division was captured, and the telomerase activity of CD117+CD34+ cardiac TCs was detected in comparison with bone mesenchymal stem cells (BMSCs), cardiac fibroblasts (CFBs), cardiomyocytes (CMs). Results: Cardiac TCs projected characteristic telopodes with thin segments (podomers) in alternation with dilation (podoms). In addition, 64% of the primary cultured cardiac TCs were composed of CD117+CD34+ cardiac TCs; which was verified by immunofluorescence. In a live cell imaging system, CD117+CD34+ cardiac TCs were observed to enter into cell division in a short time, followed by an significant invagination forming across the middle of the cell body. Using a real-time quantitative telomeric-repeat amplification assay, the telomerase concentration in CD117+CD34+ cardiac TCs was obviously lower than in BMSCs and CFBs, and significantly higher than in CMs. Conclusions: Cardiac TCs represent a unique cell population and CD117+CD34+ cardiac TCs have relative low telomerase activity that differs from BMSCs, CFBs and CMs and thus they might play an important role in maintaining cardiac homeostasis.
Collapse
Affiliation(s)
| | | | | | | | - Hua Li
- State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
| |
Collapse
|
|
26
|
Bei Y, Zhou Q, Sun Q, Xiao J. Telocytes in cardiac regeneration and repair. Semin Cell Dev Biol 2016; 55:14-21. [PMID: 26826525 DOI: 10.1016/j.semcdb.2016.01.037] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Accepted: 01/24/2016] [Indexed: 02/08/2023]
Abstract
Telocytes (TCs) are a novel type of stromal cells reported by Popescu's group in 2010. The unique feature that distinguishes TCs from other "classical" stromal cells is their extremely long and thin telopodes (Tps). As evidenced by electron microscopy, TCs are widely distributed in almost all tissues and organs. TCs contribute to form a three-dimensional interstitial network and play as active regulators in intercellular communication via homocellular/heterocellular junctions or shed vesicles. Interestingly, increasing evidence suggests the potential role of TCs in regenerative medicine. Although the heart retains some limited endogenous regenerative capacity, cardiac regenerative and repair response is however insufficient to make up the loss of cardiomyocytes upon injury. Developing novel strategies to increase cardiomyocyte renewal and repair is of great importance for the treatment of cardiac diseases. In this review, we focus on the role of TCs in cardiac regeneration and repair. We particularly describe the intercellular communication between TCs and cardiomyocytes, stem/progenitor cells, endothelial cells, and fibroblasts. Also, we discuss the current knowledge about TCs in cardiac repair after myocardial injury, as well as their potential roles in cardiac development and aging. TC-based therapy or TC-derived exosome delivery might be used as novel therapeutic strategies to promote cardiac regeneration and repair.
Collapse
Affiliation(s)
- Yihua Bei
- Regeneration and Aging Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China; Shanghai Key Laboratory of Bio-Energy Crops, School of Life Science, Shanghai University, Shanghai 200444, China
| | - Qiulian Zhou
- Regeneration and Aging Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China
| | - Qi Sun
- Regeneration and Aging Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China
| | - Junjie Xiao
- Regeneration and Aging Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China; Shanghai Key Laboratory of Bio-Energy Crops, School of Life Science, Shanghai University, Shanghai 200444, China.
| |
Collapse
|
|
27
|
Ibba-Manneschi L, Rosa I, Manetti M. Telocyte implications in human pathology: An overview. Semin Cell Dev Biol 2016; 55:62-9. [PMID: 26805444 DOI: 10.1016/j.semcdb.2016.01.022] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Accepted: 01/18/2016] [Indexed: 12/23/2022]
Abstract
Telocytes are a recently described interstitial cell population widely distributed in the stromal compartment of many organs in vertebrates, including humans. Owing to their close spatial relationship with multiple cell types, telocytes are universally considered as 'connecting cells' mostly committed to intercellular signaling by converting the interstitium into an integrated system that drives organ development and contributes to the maintenance of local tissue homeostasis. Increasing evidence indicates that telocytes may cooperate with tissue-resident stem cells to foster organ repair and regeneration, and that telocyte damage and dysfunction may occur in several disorders. The goal of this review is to provide an overview of the most recent findings concerning the implication of telocytes in a variety of pathologic conditions in humans, including heart disease, chronic inflammation and multiorgan fibrosis. Based on recent promising experimental data, there is realistic hope that by targeting telocytes alone or in tandem with stem cells, we might be able to promote organ regeneration and/or prevent irreversible end-stage organ damage in different pathologies.
Collapse
Affiliation(s)
- Lidia Ibba-Manneschi
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy
| | - Irene Rosa
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy
| | - Mirko Manetti
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy.
| |
Collapse
|
|
28
|
Paracrine Signaling in the Prostatic Stroma: A Novel Role for the Telocytes Revealed in Rodents’ Ventral Prostate. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 913:193-206. [DOI: 10.1007/978-981-10-1061-3_13] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
|
|
29
|
Abstract
Telocytes (TCs) are a novel type of interstitial cells, with extremely long and thin cellular prolongations termed telopodes (Tps). TCs were first identified by Popescu et al. and described their finding as "cells with telopodes." The presence of TCs has been reported in the majority of tissues and organs (for details please visit www.telocytes.com ). TCs have been ignored or overlooked for a long time due to our inability to observe these cells via a light microscopy. TCs represent a distinct cell population, different from other types of interstitial cells, based on their distinct (ultra)structure, immunophenotype, microRNA profile, gene feature, proteome signature, and secretome features. As TCs have been suggested as new cellular targets for forthcoming therapies, developing specific methods to modulate TC numbers represents an important objective.
Collapse
Affiliation(s)
- Junjie Xiao
- Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai, 200444, China.
| | - Yihua Bei
- Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai, 200444, China
| |
Collapse
|
|
30
|
Zheng Y, Wang X. Roles of Telocytes in the Development of Angiogenesis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 913:253-261. [DOI: 10.1007/978-981-10-1061-3_17] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
|
|
31
|
Zhu Y, Zheng M, Song D, Ye L, Wang X. Global comparison of chromosome X genes of pulmonary telocytes with mesenchymal stem cells, fibroblasts, alveolar type II cells, airway epithelial cells, and lymphocytes. J Transl Med 2015; 13:318. [PMID: 26416664 PMCID: PMC4587873 DOI: 10.1186/s12967-015-0669-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 09/11/2015] [Indexed: 02/05/2023] Open
Abstract
Background Telocytes (TCs) are suggested as a new type of interstitial cells with specific telopodes. Our previous study evidenced that TCs differed from fibroblasts and stem cells at the aspect of gene expression profiles. The present study aims to search the characters and patterns of chromosome X genes of TC-specific or TC-dominated gene profiles and fingerprints, investigate the network of principle genes, and explore potential functional association. Methods We compared gene expression profiles in chromosome X of pulmonary TCs with mesenchymal stem cells (MSC), fibroblasts (Fb), alveolar type II cells (ATII), airway basal cells (ABC), proximal airway cells (PAC), CD8+ T cells come from bronchial lymph nodes (T-BL), or CD8+ T cells from lungs (T-L) by global analyses, and selected the genes which were consistently up or down regulated (>1 fold) in TCs compared to other cells as TC-specific genes. The functional and characteristic networks were identified and compared by bioinformatics tools. Results We selected 31 chromosome X genes as the TC-specific or dominated genes, among which 8 up-regulated (Flna, Msn, Cfp, Col4a5, Mum1l1, Rnf128, Syn1, and Srpx2) and 23 down-regulated (Abcb7, Atf1, Ddx26b, Drp2, Fam122b, Gyk, Irak1, Lamp2, Mecp2, Ndufb11, Ogt, Pdha1, Pola1, Rab9, Rbmx2, Rhox9, Thoc2, Vbp1, Dkc1, Nkrf, Piga, Tmlhe and Tsr2), as compared with other cells. Conclusions Our data suggested that gene expressions of chromosome X in TCs are different with those in other cells in the lung tissue. According to the selected TC-specific genes, we infer that pulmonary TCs function as modulators which may enhance cellular growth and migration, resist senescence, protect cells from external stress, regulate immune responses, participate in tissue remodeling and repair, regulate neural function, and promote vessel formation. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0669-8) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Yichun Zhu
- Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Bioinformatics, Fudan University, Shanghai, China.
| | - Minghuan Zheng
- Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Bioinformatics, Fudan University, Shanghai, China.
| | - Dongli Song
- Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Bioinformatics, Fudan University, Shanghai, China.
| | - Ling Ye
- Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Bioinformatics, Fudan University, Shanghai, China.
| | - Xiangdong Wang
- Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Bioinformatics, Fudan University, Shanghai, China.
| |
Collapse
|
|
32
|
Richter M, Kostin S. The failing human heart is characterized by decreased numbers of telocytes as result of apoptosis and altered extracellular matrix composition. J Cell Mol Med 2015; 19:2597-606. [PMID: 26311501 PMCID: PMC4627565 DOI: 10.1111/jcmm.12664] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Accepted: 06/30/2015] [Indexed: 12/23/2022] Open
Abstract
Telocytes (TCs) are a novel type of interstitial cells only recently described. This study aimed at characterizing and quantifying TCs and telopodes (Tps) in normal and diseased hearts. We have been suggested that TCs are influenced by the extracellular matrix (ECM) composition. We used transmission electron microscopy and c-kit immunolabelling to identify and quantify TCs in explanted human hearts with heart failure (HF) because of dilated, ischemic or inflammatory cardiomyopathy. LV myectomy samples from patients with aortic stenosis with preserved ejection fraction and samples from donor hearts which could not be used for transplantation served as controls. Quantitative immunoconfocal analysis revealed that 1 mm2 of the normal myocardium contains 14.9 ± 3.4 TCs and 41.6 ± 5.9 Tps. As compared with the control group, the number of TCs and Tps in HF decreased more than twofold. There were no differences between HF and control in the number of Ki67-positive TCs. In contrast, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive TCs increased threefold in diseased hearts as compared to control. Significant inverse correlations were found between the amount of mature fibrillar collagen type I and the number of TCs (r = −0.84; P < 0.01) and Tps (r = −0.85; P < 0.01). The levels of degraded collagens showed a significant positive relationship with the TCs numbers. It is concluded that in HF the number of TCs are decreased because of higher rates of TCs apoptosis. Moreover, our results indicate that a close relationship exists between TCs and the ECM protein composition such that the number of TCs and Tps correlates negatively with the amount of mature fibrillar collagens and correlates positively with degraded collagens.
Collapse
Affiliation(s)
- Manfred Richter
- Department of Cardiac Surgery, Kerckhoff-Clinic, Bad Nauheim, Germany
| | - Sawa Kostin
- Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany
| |
Collapse
|
|
33
|
Yang J, Chi C, Liu Z, Yang G, Shen ZJ, Yang XJ. Ultrastructure damage of oviduct telocytes in rat model of acute salpingitis. J Cell Mol Med 2015; 19:1720-1728. [PMID: 25753567 PMCID: PMC4511368 DOI: 10.1111/jcmm.12548] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 01/08/2015] [Indexed: 12/22/2022] Open
Abstract
Acute salpingitis (AS) is an inflammatory disease which causes severe damage to a subset of classically described cells lining in oviduct wall and contributes to interstitial fibrosis and fertility problems. Telocytes (TCs), a newly discovered peculiar type of stromal cells, have been identified in many organs, including oviduct, with proposed multiple potential bio-functions. However, with recent increasing reports regarding TCs alterations in disease-affected tissues, there is still lack of evidence about TCs involvement in AS-affected oviduct tissues and potential pathophysiological roles. We presently identified normal TCs by their characteristic ultrastructural features and immunophenotype. However, in AS-affected oviduct tissues, TCs displayed multiple ultrastructural damage both in cellular body and prolongations, with obvious loss of TCs and development of tissue fibrosis. Furthermore, TCs lose their interstitial 3-D network connected by homocellular or heterocellular junctions between TCs and adjacent cells. And especially, TCs connected to the activated immunocytes (mononuclear cells, eosinophils) and affected local immune state (repression or activation). Meanwhile, massive neutrophils infiltration and overproduced Inducible Nitric Oxide Synthase (iNOS), COX-2, suggested mechanism of inflammatory-induced TCs damage. Consequently, TCs damage might contribute to AS-induced structural and reproductive functional abnormalities of oviduct, probably via: (i) substances, energy and functional insufficiency, presumably, e.g. TC-specific genetic material profiles, ion channels, cytoskeletal elements, Tps dynamics, etc., (ii) impaired TCs-mediated multicellular signalling, such as homeostasis/angiogenesis, tissue repair/regeneration, neurotransmission, (iii) derangement of 3-D network and impaired mechanical support for TCs-mediated multicellular signals within the stromal compartment, consequently induced interstitial fibrosis, (iv) involvement in local inflammatory process/ immunoregulation and possibly immune-mediated early pregnancy failure.
Collapse
Affiliation(s)
- Jian Yang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversitySuzhou, China
| | - Chi Chi
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversitySuzhou, China
| | - Zhen Liu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversitySuzhou, China
| | - Gang Yang
- Lab Center, Medical College of Soochow UniversitySuzhou, China
| | - Zong-Ji Shen
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversitySuzhou, China
| | - Xiao-Jun Yang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversitySuzhou, China
| |
Collapse
|
|
34
|
Bei Y, Wang F, Yang C, Xiao J. Telocytes in regenerative medicine. J Cell Mol Med 2015; 19:1441-54. [PMID: 26059693 PMCID: PMC4511344 DOI: 10.1111/jcmm.12594] [Citation(s) in RCA: 110] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Accepted: 03/15/2015] [Indexed: 12/13/2022] Open
Abstract
Telocytes (TCs) are a distinct type of interstitial cells characterized by a small cell body and extremely long and thin telopodes (Tps). The presence of TCs has been documented in many tissues and organs (go to http://www.telocytes.com). Functionally, TCs form a three-dimensional (3D) interstitial network by homocellular and heterocellular communication and are involved in the maintenance of tissue homeostasis. As important interstitial cells to guide or nurse putative stem and progenitor cells in stem cell niches in a spectrum of tissues and organs, TCs contribute to tissue repair and regeneration. This review focuses on the latest progresses regarding TCs in the repair and regeneration of different tissues and organs, including heart, lung, skeletal muscle, skin, meninges and choroid plexus, eye, liver, uterus and urinary system. By targeting TCs alone or in tandem with stem cells, we might promote regeneration and prevent the evolution to irreversible tissue damage. Exploring pharmacological or non-pharmacological methods to enhance the growth of TCs would be a novel therapeutic strategy besides exogenous transplantation for many diseased disorders.
Collapse
Affiliation(s)
- Yihua Bei
- Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai UniversityShanghai, China
| | - Fei Wang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Shanghai Tongji Hospital, Tongji University School of MedicineShanghai, China
| | - Changqing Yang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Shanghai Tongji Hospital, Tongji University School of MedicineShanghai, China
| | - Junjie Xiao
- Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai UniversityShanghai, China
| |
Collapse
|
|
35
|
Manole CG, Gherghiceanu M, Simionescu O. Telocyte dynamics in psoriasis. J Cell Mol Med 2015; 19:1504-19. [PMID: 25991475 PMCID: PMC4511349 DOI: 10.1111/jcmm.12601] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Accepted: 04/03/2015] [Indexed: 12/18/2022] Open
Abstract
The presence of telocytes (TCs) as distinct interstitial cells was previously documented in human dermis. TCs are interstitial cells completely different than dermal fibroblasts. TCs are interconnected in normal dermis in a 3D network and may be involved in skin homeostasis, remodelling, regeneration and repair. The number, distribution and ultrastructure of TCs were recently shown to be affected in systemic scleroderma. Psoriasis is a common inflammatory skin condition (estimated to affect about 0.1-11.8% of population), a keratinization disorder on a genetic background. In psoriasis, the dermis contribution to pathogenesis is frequently eclipsed by remarkable epidermal phenomena. Because of the particular distribution of TCs around blood vessels, we have investigated TCs in the dermis of patients with psoriasis vulgaris using immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy (TEM). IHC and IF revealed that CD34/PDGFRα-positive TCs are present in human papillary dermis. More TCs were present in the dermis of uninvolved skin and treated skin than in psoriatic dermis. In uninvolved skin, TEM revealed TCs with typical ultrastructural features being involved in a 3D interstitial network in close vicinity to blood vessels in contact with immunoreactive cells in normal and treated skin. In contrast, the number of TCs was significantly decreased in psoriatic plaque. The remaining TCs demonstrated multiple degenerative features: apoptosis, membrane disintegration, cytoplasm fragmentation and nuclear extrusion. We also found changes in the phenotype of vascular smooth muscle cells in small blood vessels that lost the protective envelope formed by TCs. Therefore, impaired TCs could be a 'missed' trigger for the characteristic vascular pathology in psoriasis. Our data explain the mechanism of Auspitz's sign, the most pathognomonic clinical sign of psoriasis vulgaris. This study offers new insights on the cellularity of psoriatic lesions and we suggest that TCs should be considered new cellular targets in forthcoming therapies.
Collapse
Affiliation(s)
- C G Manole
- Department of Cell Biology and Histology, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.,Laboratory of Ultrastructural Research, 'Victor Babeş' National Institute of Pathology, Bucharest, Romania
| | - Mihaela Gherghiceanu
- Laboratory of Ultrastructural Research, 'Victor Babeş' National Institute of Pathology, Bucharest, Romania
| | - Olga Simionescu
- Department of Dermatology, Colentina University Hospital, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania
| |
Collapse
|
|
36
|
Li H, Zhang H, Yang L, Lu S, Ge J. Telocytes in mice bone marrow: electron microscope evidence. J Cell Mol Med 2015; 18:975-8. [PMID: 25059385 PMCID: PMC4508138 DOI: 10.1111/jcmm.12337] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Accepted: 04/26/2014] [Indexed: 12/27/2022] Open
Abstract
Telocytes (TCs) are a novel type of interstitial cell of whom presence has been recently documented in many tissues and organs. However, whether TCs exists in bone marrow is still not reported. This study aims to find out TCs in mice bone marrow by using scanning electron microscope (SEM) and transmission electron microscope (TEM). SEM images showed that in mice bone marrow most of TCs have small spherical cell body (usually 4-6 μm diameter) with thin long telopodes (Tps; usually one to three). The longest Tp observed was about 70 μm, with an uneven calibre. Direct intercellular contacts exist between TCs. TEM shows mitochondria within dilations of Tps. Also, by TEM, we show the close spatial relations of Tps with blood vessels. In conclusion, this study provides ultrastructural evidence regarding the existence of TCs in mice bone marrow, in situ.
Collapse
Affiliation(s)
- Hua Li
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Physiology and Medicine/Cardiology, University of California, Los Angeles, CA, USA
| | | | | | | | | |
Collapse
|
|
37
|
Sun X, Zheng M, Zhang M, Qian M, Zheng Y, Li M, Cretoiu D, Chen C, Chen L, Popescu LM, Wang X. Differences in the expression of chromosome 1 genes between lung telocytes and other cells: mesenchymal stem cells, fibroblasts, alveolar type II cells, airway epithelial cells and lymphocytes. J Cell Mol Med 2015; 18:801-10. [PMID: 24826900 PMCID: PMC4119386 DOI: 10.1111/jcmm.12302] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2014] [Accepted: 03/21/2014] [Indexed: 01/18/2023] Open
Abstract
Telocytes (TCs) are a unique type of interstitial cells with specific, extremely long prolongations named telopodes (Tps). Our previous study showed that TCs are distinct from fibroblasts (Fbs) and mesenchymal stem cells (MSCs) as concerns gene expression and proteomics. The present study explores patterns of mouse TC-specific gene profiles on chromosome 1. We investigated the network of main genes and the potential functional correlations. We compared gene expression profiles of mouse pulmonary TCs, MSCs, Fbs, alveolar type II cells (ATII), airway basal cells (ABCs), proximal airway cells (PACs), CD8+ T cells from bronchial lymph nodes (T-BL) and CD8+ T cells from lungs (T-LL). The functional and feature networks were identified and compared by bioinformatics tools. Our data showed that on TC chromosome 1, there are about 25% up-regulated and 70% down-regulated genes (more than onefold) as compared with the other cells respectively. Capn2, Fhl2 and Qsox1 were over-expressed in TCs compared to the other cells, indicating that biological functions of TCs are mainly associated with morphogenesis and local tissue homoeostasis. TCs seem to have important roles in the prevention of tissue inflammation and fibrogenesis development in lung inflammatory diseases and as modulators of immune cell response. In conclusion, TCs are distinct from the other cell types.
Collapse
Affiliation(s)
- Xiaoru Sun
- Department of Pulmonary Medicine, Fudan University, Zhongshan Hospital, Shanghai Respiratory Research Institute, Shanghai, China; Department of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
38
|
Wang J, Ye L, Jin M, Wang X. Global analyses of Chromosome 17 and 18 genes of lung telocytes compared with mesenchymal stem cells, fibroblasts, alveolar type II cells, airway epithelial cells, and lymphocytes. Biol Direct 2015; 10:9. [PMID: 25888380 PMCID: PMC4355521 DOI: 10.1186/s13062-015-0042-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2014] [Accepted: 02/10/2015] [Indexed: 12/15/2022] Open
Abstract
Background Telocytes (TCs) is an interstitial cell with extremely long and thin telopodes (Tps) with thin segments (podomers) and dilations (podoms) to interact with neighboring cells. TCs have been found in different organs, while there is still a lack of TCs-specific biomarkers to distinguish TCs from the other cells. Results We compared gene expression profiles of murine pulmonary TCs on days 5 (TC5) and days 10 (TC10) with mesenchymal stem cells (MSCs), fibroblasts (Fbs), alveolar type II cells (ATII), airway basal cells (ABCs), proximal airway cells (PACs), CD8+ T cells from bronchial lymph nodes (T-BL), and CD8+ T cells from lungs (T-LL). The chromosome 17 and 18 genes were extracted for further analysis. The TCs-specific genes and functional networks were identified and analyzed by bioinformatics tools. 16 and 10 of TCs-specific genes were up-regulated and 68 and 22 were down-regulated in chromosome 17 and 18, as compared with other cells respectively. Of them, Mapk14 and Trem2 were up-regulated to indicate the biological function of TCs in immune regulation, and up-regulated MCFD2 and down-regulated E4F1 and PDCD2 had an association with tissue homeostasis for TCs. Over-expressed Dpysl3 may promote TCs self-proliferation and cell-cell network forming. Conclusions The differential gene expression in chromosomes 17 and 18 clearly revealed that TCs were the distinctive type of interstitial cells. Our data also indicates that TCs may play a dual role in immune surveillance and immune homoeostasis to keep from immune disorder in acute and chronic pulmonary diseases. TCs also participated in proliferation, differentiation and regeneration. Reviewers This article was reviewed by Qing Kay Li and Dragos Cretoiu. Electronic supplementary material The online version of this article (doi:10.1186/s13062-015-0042-0) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Jian Wang
- Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Biomedical Research Center, Fudan University Medical School, Shanghai, China.
| | - Ling Ye
- Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Biomedical Research Center, Fudan University Medical School, Shanghai, China.
| | - Meiling Jin
- Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Biomedical Research Center, Fudan University Medical School, Shanghai, China.
| | - Xiangdong Wang
- Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Biomedical Research Center, Fudan University Medical School, Shanghai, China.
| |
Collapse
|
|
39
|
Roatesi I, Radu BM, Cretoiu D, Cretoiu SM. Uterine Telocytes: A Review of Current Knowledge. Biol Reprod 2015; 93:10. [PMID: 25695721 DOI: 10.1095/biolreprod.114.125906] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2014] [Accepted: 02/10/2015] [Indexed: 01/05/2023] Open
Abstract
Telocytes (TCs), a novel cell type, are briefly defined as interstitial cells with telopodes (Tps). However, a specific immunocytochemical marker has not yet been found; therefore, electron microscopy is currently the only accurate method for identifying TCs. TCs are considered to have a mesenchymal origin. Recently proteomic analysis, microarray-based gene expression analysis, and the micro-RNA signature clearly showed that TCs are different from fibroblasts, mesenchymal stem cells, and endothelial cells. The dynamics of Tps were also revealed, and some electrophysiological properties of TCs were described (such as membrane capacitance, input resistance, membrane resting potential, and absence of action potentials correlated with different ionic currents characteristics), which can be used to distinguish uterine TCs from smooth muscle cells (SMCs). Here, we briefly present the most recent findings on the characteristics of TCs and their functions in human pregnant and nonpregnant uteri.
Collapse
Affiliation(s)
- Iurie Roatesi
- Victor Babeş National Institute of Pathology, Bucharest, Romania Division of Cell Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Beatrice Mihaela Radu
- Department of Neurological and Movement Sciences, University of Verona, Verona, Italy Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest, Romania
| | - Dragos Cretoiu
- Victor Babeş National Institute of Pathology, Bucharest, Romania Division of Cell Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Sanda Maria Cretoiu
- Victor Babeş National Institute of Pathology, Bucharest, Romania Division of Cell Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| |
Collapse
|
|
40
|
Yang XJ, Yang J, Liu Z, Yang G, Shen ZJ. Telocytes damage in endometriosis-affected rat oviduct and potential impact on fertility. J Cell Mol Med 2015; 19:452-462. [PMID: 25388530 PMCID: PMC4407595 DOI: 10.1111/jcmm.12427] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Accepted: 08/14/2014] [Indexed: 12/28/2022] Open
Abstract
Women with endometriosis (EMs) have unexplained infertility. The recently identified telocytes (TCs) might participate in the maintenance of structural and functional integrity of oviduct tissue, but so far the involvement of TCs in EMs-affected oviduct tissue and potential impact on fertility capacity remain unknown. By an integrated technique of haematoxylin and eosin staining, in situ immunohistochemistry and double-labelled immunofluorescence staining and electron microscopy approach, TCs were studied in the autotransplantation Sprague-Dawley rat model of EMs-affected oviduct tissue and in sham control, respectively, together with determination of iNOS, COX-2, LPO and estradiol. TCs were found in perivascular connective tissue and smooth muscle bundles in sham oviduct, with typical ultrastructural features (a slender piriform/spindle/triangular cell body, and one or more extremely long prolongations, emerged from cell bodies and extend to various directions), and specific immunophenotype of CD34-positive/vimentin-positive/c-kit-negative. However, in EMs-affected oviduct tissue (grade III), extensive ultrastructural damage (degeneration, discontinue, dissolution and destruction), significant decrease or loss of TCs and interstitial fibrosis were observed, together with elevated level of iNOS, COX-2, LPO and estradiol, thus suggestive of inflammation and ischaemia-induced TCs damage. Based on TCs distribution and intercellular connections, we proposed that such damage might be involved in structural and functional abnormalities of oviduct, such as attenuated intercellular signalling and oviduct contractility, impaired immunoregulation and stem cell-mediated tissue repair, 3-D interstitial architectural derangement and tissue fibrosis. Therefore, TCs damage might provide a new explanation and potential target for EMs-induced tubal damage and fertility disorders.
Collapse
Affiliation(s)
- Xiao-Jun Yang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversitySuzhou, China
| | - Jian Yang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversitySuzhou, China
| | - Zhen Liu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversitySuzhou, China
| | - Gang Yang
- Lab Center, Medical College of Soochow UniversitySuzhou, China
| | - Zong-Ji Shen
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversitySuzhou, China
| |
Collapse
|
|
41
|
Qi G, Lin M, Xu M, Manole CG, Wang X, Zhu T. Telocytes in the human kidney cortex. J Cell Mol Med 2014; 16:3116-22. [PMID: 23241355 PMCID: PMC4393739 DOI: 10.1111/j.1582-4934.2012.01582.x] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2012] [Accepted: 04/17/2012] [Indexed: 02/06/2023] Open
Abstract
Renal interstitial cells play an important role in the physiology and pathology of the kidneys. As a novel type of interstitial cell, telocytes (TCs) have been described in various tissues and organs, including the heart, lung, skeletal muscle, urinary tract, etc. (www.telocytes.com). However, it is not known if TCs are present in the kidney interstitium. We demonstrated the presence of TCs in human kidney cortex interstitium using primary cell culture, transmission electron microscopy (TEM) and in situ immunohistochemistry (IHC). Renal TCs were positive for CD34, CD117 and vimentin. They were localized in the kidney cortex interstitial compartment, partially covering the tubules and vascular walls. Morphologically, renal TCs resemble TCs described in other organs, with very long telopodes (Tps) composed of thin segments (podomers) and dilated segments (podoms). However, their possible roles (beyond intercellular signalling) as well as their specific phenotype in the kidney remain to be established.
Collapse
Affiliation(s)
- Guisheng Qi
- Department of Urology, Fudan University Zhongshan Hospital, Shanghai, China
| | | | | | | | | | | |
Collapse
|
|
42
|
Zheng Y, Chen X, Qian M, Zhang M, Zhang D, Bai C, Wang Q, Wang X. Human lung telocytes could promote the proliferation and angiogenesis of human pulmonary microvascular endothelial cells in vitro. MOLECULAR AND CELLULAR THERAPIES 2014; 2:3. [PMID: 26056572 PMCID: PMC4452074 DOI: 10.1186/2052-8426-2-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Accepted: 11/22/2013] [Indexed: 01/11/2023]
Abstract
BACKGROUND In the previous studies, telocytes were found near the capillaries in many tissues, especially on the extracellular matrix of blood vessels and positive to CD34 and c-kit. Therefore, the present study aimed to explore if telocytes could produce angiogenesis associated cytokines, promote the proliferation and the angiogenesis of vascular endothelial cells in vitro. METHODS Human lung telocytes were isolated and cultured, and were identified by immunofluorescence cytochemistry with CD34, c-kit and vimentin. Telocytes conditional media (TCM) was prepared, and the expressions of angiogenesis associated cytokines in TCM were detected by ELISA. Human pulmonary microvascular endothelial cells (HPMECs) were cultured with DMEM media or TCM for 72 hours. The proliferation of HPMECs was continuously detected with CCK-8 kit at an interval of 12 hours. HPMECs were also injured by lipopolysaccharide, and cultured with TCM and DMEM respectively, and the tube formation capacity was detected. RESULTS Telocytes were positive for CD34, c-kit and vimentin. The expressions of VEGF and EGF in TCM were significantly higher, the proliferation of HPMECs cultured with TCM significantly increased, and the tube formation of HPMECs injured by endotoxin was improved with the culture of TCM, as compared with the culture of DMEM. CONCLUSION The present study provides the evidence that human lung telocytes could produce the growth factors, such as VEGF and EGF. Telocytes conditional media induced the proliferation of pulmonary endothelial cells and prevented from endotoxin-induced compromise of pulmonary endothelial angiogenesis.
Collapse
Affiliation(s)
- Yonghua Zheng
- />Department of Respiratory Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University School of Medicine, Fenglin Rd, No 180, Xuhui Dist, Shanghai, 320003 China
| | - Xiaoke Chen
- />Department of thoracic surgery, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University School of Medicine, Fenglin Rd, No 180, Xuhui Dist, Shanghai, 320003 China
| | - Mengjia Qian
- />Biomedical Research Center, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University School of Medicine, Fenglin Rd, No 180, Xuhui Dist, Shanghai, 320003 China
| | - Miaomiao Zhang
- />Biomedical Research Center, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University School of Medicine, Fenglin Rd, No 180, Xuhui Dist, Shanghai, 320003 China
| | - Ding Zhang
- />Department of Respiratory Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University School of Medicine, Fenglin Rd, No 180, Xuhui Dist, Shanghai, 320003 China
| | - Chunxue Bai
- />Department of Respiratory Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University School of Medicine, Fenglin Rd, No 180, Xuhui Dist, Shanghai, 320003 China
| | - Qun Wang
- />Department of thoracic surgery, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University School of Medicine, Fenglin Rd, No 180, Xuhui Dist, Shanghai, 320003 China
| | - Xiangdong Wang
- />Department of Respiratory Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University School of Medicine, Fenglin Rd, No 180, Xuhui Dist, Shanghai, 320003 China
| |
Collapse
|
|
43
|
Zheng Y, Zhang M, Qian M, Wang L, Cismasiu VB, Bai C, Popescu LM, Wang X. Genetic comparison of mouse lung telocytes with mesenchymal stem cells and fibroblasts. J Cell Mol Med 2013; 17:567-77. [PMID: 23621815 PMCID: PMC3822657 DOI: 10.1111/jcmm.12052] [Citation(s) in RCA: 121] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2012] [Revised: 12/20/2012] [Accepted: 12/20/2012] [Indexed: 12/23/2022] Open
Abstract
Telocytes (TCs) are interstitial cells with telopodes – very long prolongations that establish intercellular contacts with various types of cells. Telocytes have been found in many organs and various species and have been characterized ultrastructurally, immunophenotypically and electrophysiologically (http://www.telocytes.com). Telocytes are distributed through organ stroma forming a three-dimensional network in close contacts with blood vessels, nerve bundles and cells of the local immune system. Moreover, it has been shown that TCs express a broad range of microRNAs, such as pro-angiogenic and stromal-specific miRs. In this study, the gene expression profile of murine lung TCs is compared with other differentiated interstitial cells (fibroblasts) and with stromal stem/progenitor cells. More than 2000 and 4000 genes were found up- or down-regulated, respectively, in TCs as compared with either MSCs or fibroblasts. Several components or regulators of the vascular basement membrane are highly expressed in TCs, such as Nidogen, Collagen type IV and Tissue Inhibitor of Metalloproteinase 3 (TIMP3). Given that TCs locate in close vicinity of small vessels and capillaries, the data suggest the implication of TCs in vascular branching. Telocytes express also matrix metalloproteases Mmp3 and Mmp10, and thus could regulate extracellular matrix during vascular branching and de novo vessel formation. In conclusion, our data show that TCs are not fibroblasts, as the ultrastructure, immunocytochemistry and microRNA assay previously indicated. Gene expression profile demonstrates that TCs are functionally distinct interstitial cells with specific roles in cell signalling, tissue remodelling and angiogenesis.
Collapse
Affiliation(s)
- Yonghua Zheng
- Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Chen X, Zheng Y, Manole CG, Wang X, Wang Q. Telocytes in human oesophagus. J Cell Mol Med 2013; 17:1506-12. [PMID: 24188731 PMCID: PMC4117563 DOI: 10.1111/jcmm.12149] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2013] [Accepted: 08/24/2013] [Indexed: 12/17/2022] Open
Abstract
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.
Collapse
Affiliation(s)
- Xiaoke Chen
- Department of thoracic surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | | | | | | | | |
Collapse
|
|
45
|
Bassotti G, Villanacci V, Creƫoiu D, Creƫoiu SM, Becheanu G. Cellular and molecular basis of chronic constipation: taking the functional/idiopathic label out. World J Gastroenterol 2013; 19:4099-4105. [PMID: 23864772 PMCID: PMC3710411 DOI: 10.3748/wjg.v19.i26.4099] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Revised: 05/16/2013] [Accepted: 05/18/2013] [Indexed: 02/06/2023] Open
Abstract
In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called "functional" or "idiopathic" disease, where conditions thought for decades to be based mainly on alterations of visceral perception or aberrant psychosomatic mechanisms have, in fact, be reconducted to an organic basis (or, at the very least, have shown one or more demonstrable abnormalities). This is particularly true, for instance, for irritable bowel syndrome, the prototype entity of "functional" gastrointestinal disorders, where low-grade inflammation of both mucosa and myenteric plexus has been repeatedly demonstrated. Thus, researchers have also investigated other functional/idiopathic gastrointestinal disorders, and found that some organic ground is present, such as abnormal neurotransmission and myenteric plexitis in esophageal achalasia and mucosal immune activation and mild eosinophilia in functional dyspepsia. Here we show evidence, based on our own and other authors' work, that chronic constipation has several abnormalities reconductable to alterations in the enteric nervous system, abnormalities mainly characterized by a constant decrease of enteric glial cells and interstitial cells of Cajal (and, sometimes, of enteric neurons). Thus, we feel that (at least some forms of) chronic constipation should no more be considered as a functional/idiopathic gastrointestinal disorder, but instead as a true enteric neuropathic abnormality.
Collapse
|
|
46
|
Cretoiu SM, Cretoiu D, Marin A, Radu BM, Popescu LM. Telocytes: ultrastructural, immunohistochemical and electrophysiological characteristics in human myometrium. Reproduction 2013; 145:357-70. [PMID: 23404846 PMCID: PMC3636525 DOI: 10.1530/rep-12-0369] [Citation(s) in RCA: 131] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Telocytes (TCs) have been described in various organs and species (www.telocytes.com) as cells with telopodes (Tps) – very long cellular extensions with an alternation of thin segments (podomers) and dilated portions (podoms). We examined TCs using electron microscopy (EM), immunohistochemistry (IHC), immunofluorescence (IF), time-lapse videomicroscopy and whole-cell patch voltage clamp. EM showed a three-dimensional network of dichotomous-branching Tps, a labyrinthine system with homocellular and heterocellular junctions. Tps release extracellular vesicles (mean diameter of 160.6±6.9 nm in non-pregnant myometrium and 171.6±4.6 nm in pregnant myometrium), sending macromolecular signals to neighbouring cells. Comparative measurements (non-pregnant and pregnant myometrium) of podomer thickness revealed values of 81.94±1.77 vs 75.53±1.81 nm, while the podoms' diameters were 268.6±8.27 vs 316.38±17.56 nm. IHC as well as IF revealed double c-kit and CD34 positive results. Time-lapse videomicroscopy of cell culture showed dynamic interactions between Tps and myocytes. In non-pregnant myometrium, patch-clamp recordings of TCs revealed a hyperpolarisation-activated chloride inward current with calcium dependence and the absence of L-type calcium channels. TCs seem to have no excitable properties similar to the surrounding smooth muscle cells (SMCs). In conclusion, this study shows the presence of TCs as a distinct cell type in human non-pregnant and pregnant myometrium and describes morphometric differences between the two physiological states. In addition, we provide a preliminary in vitro electrophysiological evaluation of the non-pregnant state, suggesting that TCs could influence timing of the contractile activity of SMCs.
Collapse
Affiliation(s)
- Sanda M Cretoiu
- Division of Cellular and Molecular Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest 050474, Romania
| | | | | | | | | |
Collapse
|
|
47
|
Manetti M, Guiducci S, Ruffo M, Rosa I, Faussone-Pellegrini MS, Matucci-Cerinic M, Ibba-Manneschi L. Evidence for progressive reduction and loss of telocytes in the dermal cellular network of systemic sclerosis. J Cell Mol Med 2013; 17:482-96. [PMID: 23444845 PMCID: PMC3822649 DOI: 10.1111/jcmm.12028] [Citation(s) in RCA: 130] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Accepted: 12/22/2012] [Indexed: 12/17/2022] Open
Abstract
Telocytes, a peculiar type of stromal cells, have been recently identified in a variety of tissues and organs, including human skin. Systemic sclerosis (SSc, scleroderma) is a complex connective tissue disease characterized by fibrosis of the skin and internal organs. We presently investigated telocyte distribution and features in the skin of SSc patients compared with normal skin. By an integrated immunohistochemical and transmission electron microscopy approach, we confirmed that telocytes were present in human dermis, where they were mainly recognizable by their typical ultrastructural features and were immunophenotypically characterized by CD34 expression. Our findings also showed that dermal telocytes were immunophenotypically negative for CD31/PECAM-1 (endothelial cells), α-SMA (myofibroblasts, pericytes, vascular smooth muscle cells), CD11c (dendritic cells, macrophages), CD90/Thy-1 (fibroblasts) and c-kit/CD117 (mast cells). In normal skin, telocytes were organized to form three-dimensional networks distributed among collagen bundles and elastic fibres, and surrounded microvessels, nerves and skin adnexa (hair follicles, sebaceous and sweat glands). Telocytes displayed severe ultrastructural damages (swollen mitochondria, cytoplasmic vacuolization, lipofuscinic bodies) suggestive of ischaemia-induced cell degeneration and were progressively lost from the clinically affected skin of SSc patients. Telocyte damage and loss evolved differently according to SSc subsets and stages, being more rapid and severe in diffuse SSc. Briefly, in human skin telocytes are a distinct stromal cell population. In SSc skin, the progressive loss of telocytes might (i) contribute to the altered three-dimensional organization of the extracellular matrix, (ii) reduce the control of fibroblast, myofibroblast and mast cell activity, and (iii) impair skin regeneration and/or repair.
Collapse
Affiliation(s)
- Mirko Manetti
- Department of Anatomy, Histology and Forensic Medicine, University of Florence, I-50134 Florence, Italy.
| | | | | | | | | | | | | |
Collapse
|
|
48
|
Corradi LS, Jesus MM, Fochi RA, Vilamaior PSL, Justulin LA, Góes RM, Felisbino SL, Taboga SR. Structural and ultrastructural evidence for telocytes in prostate stroma. J Cell Mol Med 2013; 17:398-406. [PMID: 23388038 PMCID: PMC3823021 DOI: 10.1111/jcmm.12021] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2012] [Accepted: 12/28/2012] [Indexed: 12/24/2022] Open
Abstract
The prostate comprises a glandular epithelium embedded within a fibromuscular stroma. The stroma is a complex arrangement of cells and extracellular matrix (ECM) components in addition to growth factors, regulatory molecules, remodelling enzymes, blood vessels, nerves and immune cells. The principal sources of ECM components are fibroblasts and smooth muscle cells (SMC), which synthesize the structural and regulatory components of the ECM. Telocytes (TCs) were recently described as a novel stromal cell type that exhibited characteristic features. The aim of this study was to confirm the presence of TCs in prostate stromal tissue of gerbils, as the stromal compartment of this gland is a dynamic microenvironment. We used transmission electron microscopy (TEM), light microscopy and immunohistochemistry methods to provide morphological evidence for the presence of TCs. Cells that resembled TCs were observed in gerbil prostatic stroma. These cells had small cellular bodies with very thin and extremely long cellular processes. They were found primarily in the subepithelial area and also at the periphery of SMC layers. TCs also exhibited moniliform processes, caveolae and nuclei surrounded by small amounts of cytoplasm. Close contacts between TC podomers were evident, particularly in the adjacent epithelial compartment. This morphological evidence supported the presence of TCs in the gerbil prostatic stroma, which we report for the first time.
Collapse
Affiliation(s)
- Lara S Corradi
- Department of Biology, Institute of Biosciences, Humanities and Exact Sciences (IBILCE), Univ. Estadual Paulista - UNESP, São José do Rio Preto, São Paulo, Brazil
| | | | | | | | | | | | | | | |
Collapse
|
|
49
|
Ceafalan L, Gherghiceanu M, Popescu LM, Simionescu O. Telocytes in human skin--are they involved in skin regeneration? J Cell Mol Med 2012; 16:1405-20. [PMID: 22500885 PMCID: PMC3823211 DOI: 10.1111/j.1582-4934.2012.01580.x] [Citation(s) in RCA: 158] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Telocytes (TCs), a particular interstitial cell type, have been recently described in a wide variety of mammalian organs (www.telocytes.com). The TCs are identified morphologically by a small cell body and extremely long (tens to hundreds of μm), thin prolongations (less than 100 nm in diameter, below the resolving power of light microscopy) called telopodes. Here, we demonstrated with electron microscopy and immunofluorescence that TCs were present in human dermis. In particular, TCs were found in the reticular dermis, around blood vessels, in the perifollicular sheath, outside the glassy membrane and surrounding sebaceous glands, arrector pili muscles and both the secretory and excretory portions of eccrine sweat glands. Immunofluorescence screening and laser scanning confocal microscopy showed two subpopulations of dermal TCs; one expressed c-kit/CD117 and the other was positive for CD34. Both subpopulations were also positive for vimentin. The TCs were connected to each other by homocellular junctions, and they formed an interstitial 3D network. We also found TCs adjoined to stem cells in the bulge region of hair follicles. Moreover, TCs established atypical heterocellular junctions with stem cells (clusters of undifferentiated cells). Given the frequency of allergic skin pathologies, we would like to emphasize the finding that close, planar junctions were frequently observed between TCs and mast cells. In conclusion, based on TC distribution and intercellular connections, our results suggested that TCs might be involved in skin homeostasis, skin remodelling, skin regeneration and skin repair.
Collapse
Affiliation(s)
- Laura Ceafalan
- Molecular Medicine Laboratory, V. Babeş National Institute of Pathology, Bucharest, Romania
| | | | | | | |
Collapse
|
|
50
|
Creţoiu SM, Creţoiu D, Popescu LM. Human myometrium - the ultrastructural 3D network of telocytes. J Cell Mol Med 2012; 16:2844-9. [PMID: 23009098 PMCID: PMC4118253 DOI: 10.1111/j.1582-4934.2012.01651.x] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2012] [Accepted: 09/22/2012] [Indexed: 01/05/2023] Open
Abstract
Telocytes (TCs), a novel type of interstitial cells, were recently described in the interstitial space of tissues (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.
Collapse
Affiliation(s)
- Sanda M Creţoiu
- Division of Cellular and Molecular Medicine, Department of Morphological Sciences, Carol Davila University of Medicine and PharmacyBucharest, Romania
- Department of Ultrastructural Pathology, Victor Babeş National Institute of PathologyBucharest, Romania
| | - Dragos Creţoiu
- Division of Cellular and Molecular Medicine, Department of Morphological Sciences, Carol Davila University of Medicine and PharmacyBucharest, Romania
- Molecular Medicine Department, Victor Babeş National Institute of PathologyBucharest, Romania
| | - Laurentiu M Popescu
- Division of Advanced Studies, Victor Babeş National Institute of PathologyBucharest, Romania
| |
Collapse
|