Telocyte – Wikipedia

Telocytes are a novel defined type of interstitial (stromal) cells with very long (tens to hundreds of micrometres) and very thin prolongations (mostly below the resolving power of light microscopy).

Figure 1. Human non-pregnant myometrium in cell culture; day 3; the first passage. Giemsa staining. One TC establishing contacts with a myocyte by a Tp of about 65 mm long. Photographic composition of 4 serial phase contrast images; original magnification 40x. In red rectangles, a higher magnification clearly shows the moniliform aspect; at least 40 specific dilations (podoms) interconnected by thin segments (podomeres) are visible in a ‘beadlike’ fashion.

Figure 2. Digitally coloured TEM image shows TC (blue) in human subepicardium, bordering the peripheral cardiomyocytes (CM, highlighted in brown). The TC has three telopodes, illustrating: a) the distinctive dichotomous pattern of branching (arrows); b) Tp are very thin at the emergence of the cell body; c) alternating podoms and podomeres. Note that some portions of podomeres have the same thickness as collagen fibrills, which make them impossible to be observed under light microscopy. E – elastin Scale bar – 2 mm.

Figure 3. Human exocrine pancreas. TC (blue) form with their typical Tp a network around acini. Note the stromal synapse (red arrows) between a mast cell and the Tp of a TC. Courtesy of Dr. M.I. Nicolescu, Department of Cellular and Molecular Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania.

Figure 4. Human resting mammary gland stroma. One TC hallmark, namely Tp, appears very long and convoluted. Note homocellular junctions marked by red circles, as well as shed vesicles (blue) and an exosome (violet).

Figure 5. Human term placenta. The TC (blue) has few organelles in the perinuclear area and 3 emerging Tp (red arrows); black arrowheads mark the dichotomic branching points. Note the podoms and podomeres. Black arrow points the junction between a Tp and a smooth muscle cell (SMC, colored in brown). Reproduced with permission from [2].

Figure 6. Non-pregnant myometrium. Digitally colored TC (blue) with 3 Tp that encircle bundles of cross-cut smooth muscle cells (SMC, Sienna brown); N – nuclei. Reproduced with permission from [1].

Figure 7. Rat jejunum. A typical Tp (blue) located between smooth muscle cells (SMC) and nerve endings. Note a large podom and the corresponding podomeres. TC body is not captured in the image. Courtesy of Dr. D. Cretoiu, Department of Cellular and Molecular Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania.

Figure 8. Rat stomach, multicontact stromal synapses between two TC, a plasma cell and an eosinophil, respectively. 3-D image computer-aided reconstruction from 9 serial ultrathin sections; original magnification 1,500x. The upper inset shows contact points where the distance between both cell membranes (Tp membrane and plasma-cell membrane) is 15 nm or less (in violet), seen from the plasma cell cytoplasm. In the lower inset Tp were rendered transparent in order to depict the same synapse. Reproduced with permission from [22].

Rationale for the term telocyte[edit]

Professor Laurențiu M. Popescu’s group from Bucharest, Romania described a new type of cell. Popescu coined the terms telocytes (TC) for these cells, and telopodes (Tp)[1] for their extremely long but thin prolongations[1][2][3][4][5][6][7] in order to prevent further confusion with other interstitial (stromal) cells (e.g., fibroblast, fibroblast-like cells, myofibroblast, mesenchymal cells). Telopodes present an alternation of thin segments, podomeres (with caliber mostly under 200 nm, below the resolving power of light microscopy) and dilated segments, podoms, which accommodate mitochondria, (rough) endoplasmic reticulum and caveolae – the so-called “Ca2+ uptake/release units”. The concept of TC was promptly adopted by other laboratories, as well.[8][9][10][11][12][13][14][15][16][17][18]

Telocytes and/or fibroblasts ?[edit]

The interstitium (stroma) is in most of the cases seen as a connecting “device” for the specific structures of an organ. Usually, people perceive interstitial cells as being mainly (or even, only) fibroblasts. However, fibroblasts have the function of generating connective tissue matrix, specifically, collagen. The distinction between TC and fibroblasts is obvious since they have different ultrastructure and phenotype. Therefore, their functions should be mostly different: TC – intercellular signaling (connections), but fibroblasts – collagen synthesis. In other words, TC are “more” functionally oriented while fibroblasts are “more” structurally oriented, responsible for fibrosis.

There are some clear ultrastructural features that differentiate telocytes from fibroblasts. For instance, the general aspect of TC is of a small oval (piriform/spindle/triangular/stellate)-shaped cellular body, containing a nucleus surrounded by a small amount of cytoplasm. Anyway, the shape of the cell body depends on the number of Tp. TC cellular body average dimensions are, as measured on EM images, 9.3 μm ± 3.2 μm (min. 6.3μm; max. 16.4 μm). Fibroblast nucleus is typically euchromatic, but TC nucleus is mostly heterochromatic. Mitochondria represent only 2% of cell body volume and the Golgi complex is small in TC. Fibroblasts Golgi complex is prominent and the rough endoplasmic reticulum is very well developed (usually 5-12%) of cell volume.

Since telopodes are distinctive for telocytes, here are their main features:

  1. Number: 1–5 (frequently only 2–3 telopodes are observed on a single section, depending on site and angle of section, since their 3D convolutions prevent them to be observed at their full length in a 2D very thin section);
  2. Length: tens – up to hundreds of μm, as measured on EM images (e.g. Figs. 2-10). However, under favorable conditions in cell cultures, their entire length can be captured in several successive images (Fig. 1);
  3. Thickness: uneven caliber, mostly below 0.2 μm (below the resolving power of light microscopy), visible under electron microscopy;
  4. Moniliform aspect: podoms and podomeres; average caliber of podomeres: 0.1 μm ± 0.05μm, min. = 0.003 μm; max. = 0.24 μm; Podoms accommodate: mitochondria, (rough) endoplasmic reticulum, caveolae, a trio called ‘Ca2+-uptake/release units’.
  5. Branching, with a dichotomous pattern;
  6. Organization in a labyrinthine system, forming a 3D network anchored by hetero- and homocellular junctions.

Summary[edit]

Here is shown visual evidence (electron microscopy, electron tomography, phase contrast microscopy) for the existence of Telocytes (TC) in many organs from human and rodents. TC and Tp, and also podoms and podomeres were found in:

Recent evidence shows the involvement of TC in pathology.[26] TC are strategically located in between blood vessels (capillaries), nerve endings and the specific resident cell populations of a given organ. TC establish via Tp homo- and heterocellular junctions and release shed vesicles and exosomes.

Perspectives: regenerative medicine[edit]

TC and SC make a tandem (due to specific intercellular junctions) within the so-called SC niches, at least in heart[27] and lungs. Hence, TC could be key-players in regenerating and repair of some organs. The tandem TC-SC could be a better option for therapy rather than SC alone. Published studies suggest that cardiac TCs could be regarded as a potential cell source for therapeutic use to improve cardiac repair and function after a myocardial infarction, either alone or in tandem with SC.[28] Recent data show that TCs are completely different from FBs, using a quantitative proteomics approach, suggesting that TCs might play specific roles in mechanical sensing and mechanochemical conversion task, tissue homoeostasis and remodelling/renewal.[22]

Figures[edit]

See also[edit]

References[edit]

  1. ^ a b Popescu, L. M.; Faussone-Pellegrini, Maria-Simonetta (April 2010). “TELOCYTES – a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal-Like Cells (ICLC) to TELOCYTES”. Journal of Cellular and Molecular Medicine. 14 (4): 729–740. doi:10.1111/j.1582-4934.2010.01059.x. ISSN 1582-4934. PMC 3823108. PMID 20367664.
  2. ^ a b Suciu, Laura; Popescu, Laurenţiu M.; Gherghiceanu, Mihaela; Regalia, Teodor; Nicolescu, Mihnea I.; Hinescu, Mihail E.; Faussone-Pellegrini, Maria-Simonetta (2010). “Telocytes in human term placenta: morphology and phenotype”. Cells Tissues Organs. 192 (5): 325–339. doi:10.1159/000319467. ISSN 1422-6421. PMID 20664249. S2CID 27675409.
  3. ^ Popescu, L M; Manole, C G; Gherghiceanu, M; Ardelean, A; Nicolescu, M I; Hinescu, M E; Kostin, S (August 2010). “Telocytes in human epicardium”. Journal of Cellular and Molecular Medicine. 14 (8): 2085–2093. doi:10.1111/j.1582-4934.2010.01129.x. ISSN 1582-1838. PMC 3823000. PMID 20629996.
  4. ^ Gherghiceanu, Mihaela; Manole, C. G.; Popescu, L. M. (September 2010). “Telocytes in endocardium: electron microscope evidence”. Journal of Cellular and Molecular Medicine. 14 (9): 2330–2334. doi:10.1111/j.1582-4934.2010.01133.x. ISSN 1582-4934. PMC 3822573. PMID 20716125.
  5. ^ Popescu, LM; Gherghiceanu, M; Kostin, S (2011). “Telocytes and heart renewing”. In Wang, P; Kuo, CH; Takeda, N; Singal, PK (eds.). Adaptation biology and medicine, vol 6. Cell adaptations and challenges. Vol. 6. New Delhi: Narosa Publishing. pp. 17–39.
  6. ^ Gherghiceanu, Mihaela; Popescu, L M (April 2010). “Cardiomyocyte precursors and telocytes in epicardial stem cell niche: electron microscope images”. Journal of Cellular and Molecular Medicine. 14 (4): 871–877. doi:10.1111/j.1582-4934.2010.01060.x. ISSN 1582-1838. PMC 3823118. PMID 20367663.
  7. ^ a b Hinescu, Mihail E.; Gherghiceanu, Mihaela; Suciu, Laura; Popescu, Laurentiu M. (February 2011). “Telocytes in pleura: two- and three-dimensional imaging by transmission electron microscopy”. Cell and Tissue Research. 343 (2): 389–397. doi:10.1007/s00441-010-1095-0. ISSN 0302-766X. PMC 3032227. PMID 21174125.
  8. ^ Bani, Daniele; Formigli, Lucia; Gherghiceanu, Mihaela; Faussone-Pellegrini, Maria-Simonetta (October 2010). “Telocytes as supporting cells for myocardial tissue organization in developing and adult heart”. Journal of Cellular and Molecular Medicine. 14 (10): 2531–2538. doi:10.1111/j.1582-4934.2010.01119.x. ISSN 1582-4934. PMC 3823169. PMID 20977627.
  9. ^ Kostin, Sawa (July 2010). “Myocardial telocytes: a specific new cellular entity”. Journal of Cellular and Molecular Medicine. 14 (7): 1917–1921. doi:10.1111/j.1582-4934.2010.01111.x. ISSN 1582-1838. PMC 3823273. PMID 20604817.
  10. ^ Groot, Adriana C Gittenberger-de; Winter, Elisabeth M; Poelmann, Robert E (May 2010). “Epicardium-derived cells (EPDCs) in development, cardiac disease and repair of ischemia”. Journal of Cellular and Molecular Medicine. 14 (5): 1056–1060. doi:10.1111/j.1582-4934.2010.01077.x. ISSN 1582-1838. PMC 3822740. PMID 20646126.
  11. ^ D, Klumpp; Re, Horch; U, Kneser; Jp, Beier (November 2010). “Engineering skeletal muscle tissue–new perspectives in vitro and in vivo”. Journal of Cellular and Molecular Medicine. 14 (11): 2622–2629. doi:10.1111/j.1582-4934.2010.01183.x. PMC 4373482. PMID 21091904.
  12. ^ Tommila M, Granulation tissue formation. The effect of hydroxyapatite coating of cellulose on cellular differentiation. PhD Thesis, University of Turku, Finland.
  13. ^ Zhou, Jin; Zhang, Ye; Wen, Xinyu; Cao, Junkai; Li, Dexue; Lin, Qiuxia; Wang, Haibin; Liu, Zhiqiang; Duan, Cuimi; Wu, Kuiwu; Wang, Changyong (November 2010). “Telocytes accompanying cardiomyocyte in primary culture: two- and three-dimensional culture environment”. Journal of Cellular and Molecular Medicine. 14 (11): 2641–2645. doi:10.1111/j.1582-4934.2010.01186.x. ISSN 1582-1838. PMC 4373485. PMID 21158014.
  14. ^ Limana, Federica; Capogrossi, Maurizio C.; Germani, Antonia (January 2011). “The epicardium in cardiac repair: from the stem cell view”. Pharmacology & Therapeutics. 129 (1): 82–96. doi:10.1016/j.pharmthera.2010.09.002. ISSN 1879-016X. PMID 20937304.
  15. ^ Carmona, I. Cantarero; Bartolomé, M. J. Luesma; Escribano, C. Junquera (January 2011). “Identification of telocytes in the lamina propria of rat duodenum: transmission electron microscopy”. Journal of Cellular and Molecular Medicine. 15 (1): 26–30. doi:10.1111/j.1582-4934.2010.01207.x. PMC 3822490. PMID 21054782.
  16. ^ Kostin, Sawa (April 2011). “Types of Cardiomyocyte Death and Clinical Outcomes in Patients With Heart Failure”. Journal of the American College of Cardiology. 57 (14): 1532–1534. doi:10.1016/j.jacc.2010.10.049. PMID 21453831.
  17. ^ Radenkovic, Goran (January 2012). “Two patterns of development of interstitial cells of Cajal in the human duodenum”. Journal of Cellular and Molecular Medicine. 16 (1): 185–192. doi:10.1111/j.1582-4934.2011.01287.x. PMC 3823104. PMID 21352475.
  18. ^ Russell, Jamie L.; Goetsch, Sean C.; Gaiano, Nicholas R.; Hill, Joseph A.; Olson, Eric N.; Schneider, Jay W. (2011-01-07). “A dynamic notch injury response activates epicardium and contributes to fibrosis repair”. Circulation Research. 108 (1): 51–59. doi:10.1161/CIRCRESAHA.110.233262. ISSN 1524-4571. PMC 3042596. PMID 21106942.
  19. ^ Creţoiu, Sanda M.; Creţoiu, Dragos; Popescu, Laurentiu M. (November 2012). “Human myometrium – the ultrastructural 3D network of telocytes”. Journal of Cellular and Molecular Medicine. 16 (11): 2844–2849. doi:10.1111/j.1582-4934.2012.01651.x. PMC 4118253. PMID 23009098.
  20. ^ Cretoiu, Sanda M; Cretoiu, Dragos; Marin, Adela; Radu, Beatrice Mihaela; Popescu, Laurentiu M (April 2013). “Telocytes: ultrastructural, immunohistochemical and electrophysiological characteristics in human myometrium”. Reproduction. 145 (4): 357–370. doi:10.1530/REP-12-0369. ISSN 1470-1626. PMC 3636525. PMID 23404846.
  21. ^ Zheng, Y.; Li, H.; Manole, C. G.; Sun, A.; Ge, J.; Wang, X. (October 2011). “Telocytes in trachea and lungs”. Journal of Cellular and Molecular Medicine. 15 (10): 2262–2268. doi:10.1111/j.1582-4934.2011.01404.x. PMC 4394233. PMID 21810171.
  22. ^ a b Zheng, Yonghua; Cretoiu, Dragos; Yan, Guoquan; Cretoiu, Sanda Maria; Popescu, Laurentiu M.; Wang, Xiangdong (April 2014). “Comparative proteomic analysis of human lung telocytes with fibroblasts”. Journal of Cellular and Molecular Medicine. 18 (4): 568–589. doi:10.1111/jcmm.12290. PMC 4000110. PMID 24674459.
  23. ^ Nicolescu, Mihnea I.; Popescu, Laurentiu M. (August 2012). “Telocytes in the Interstitium of Human Exocrine Pancreas: Ultrastructural Evidence”. Pancreas. 41 (6): 949–956. doi:10.1097/MPA.0b013e31823fbded. ISSN 0885-3177. PMID 22318257. S2CID 23643116.
  24. ^ Li, Liping; Lin, Miao; Li, Long; Wang, Rulin; Zhang, Chao; Qi, Guisheng; Xu, Ming; Rong, Ruiming; Zhu, Tongyu (June 2014). “Renal telocytes contribute to the repair of ischemically injured renal tubules”. Journal of Cellular and Molecular Medicine. 18 (6): 1144–1156. doi:10.1111/jcmm.12274. PMC 4508154. PMID 24758589.
  25. ^ Qi, Guisheng; Lin, Miao; Xu, Ming; Manole, C. G.; Wang, Xiangdong; Zhu, Tongyu (December 2012). “Telocytes in the human kidney cortex”. Journal of Cellular and Molecular Medicine. 16 (12): 3116–3122. doi:10.1111/j.1582-4934.2012.01582.x. PMC 4393739. PMID 23241355.
  26. ^ Mandache, E.; Gherghiceanu, M.; Macarie, C.; Kostin, S.; Popescu, L. M. (December 2010). “Telocytes in human isolated atrial amyloidosis: ultrastructural remodelling”. Journal of Cellular and Molecular Medicine. 14 (12): 2739–2747. doi:10.1111/j.1582-4934.2010.01200.x. ISSN 1582-4934. PMC 3822724. PMID 21040457.
  27. ^ Polykandriotis, E.; Popescu, L. M.; Horch, R. E. (October 2010). “Regenerative medicine: then and now–an update of recent history into future possibilities”. Journal of Cellular and Molecular Medicine. 14 (10): 2350–2358. doi:10.1111/j.1582-4934.2010.01169.x. ISSN 1582-4934. PMC 3823153. PMID 20825521.
  28. ^ Zhao, Baoyin; Liao, Zhaofu; Chen, Shang; Yuan, Ziqiang; Yilin, Chen; Lee, Kenneth K.H.; Qi, Xufeng; Shen, Xiaotao; Zheng, Xin; Quinn, Thomas; Cai, Dongqing (May 2014). “Intramyocardial transplantation of cardiac telocytes decreases myocardial infarction and improves post-infarcted cardiac function in rats”. Journal of Cellular and Molecular Medicine. 18 (5): 780–789. doi:10.1111/jcmm.12259. PMC 4119384. PMID 24655344.