INTERSTITIAL PACEMAKER CELLS

Cover Page


Cite item

Full Text

Abstract

This article is devoted to interstitial Cajal cells (syn. telocytes, interstitial pacemaker cells, IPC). First those cells were discovered by C.R Cajal in the muscle coat of the gut in 1893. Nowadays they have revealed in all parts of digestive systems (from esophagus to rectum), urinary and biliary tracts, prostate, liver, the walls of arteries and lymphatics, as well Fallopian tube, myometrium, mammary glands. Characteristic ultrastructural features are elongated spindle shape, length from 40 to 100 μm, the thickness of 0.2–0.5 μm, the presence of 2–5 processes. Length of them ranging from tens to hundreds of micrometers, some of them have secondary and tertiary branching, forming a three-dimensional network. IPC having spontaneous electrical (pacemaker) activity are cause to contraction of smooth muscle cells. Depending on the location of IPC have different morphological and ultrastructural characteristics. Characteristic immunohistochemical markers are CD117, CD34, S100, vimentin. IPC replay to acetylcholine, norepinephrine, estrogen, progesterone, and nitric oxide by influence of corresponding receptors. IPC have specific gap junctions with lymphocytes, basophiles, eosinophils, neutrophils, mast cells and dendritic cells. Grave pathology of those cells are forming gastrointestinal stromal tumors.

About the authors

N. V. Nizyaeva

V.I. Kulakov Research Centre for Obstetrics, Gynecology and Perinatology, Moscow

Author for correspondence.
Email: niziaeva@gmail.com
MD, senior research scientist of the 2nd Pathology Department of V.I. Kulakov RI for Obstetrics, Gynecology and Perinatology Россия

M. V. Marei

V.I. Kulakov Research Centre for Obstetrics, Gynecology and Perinatology, Moscow

Email: mashamarei@mail.ru
junior research scientist at the Laboratory of Mitochondrial Medicine of V.I. Kulakov RI for Obstetrics, Gynecology and Perinatology Россия

G. T. Sukhikh

V.I. Kulakov Research Centre for Obstetrics, Gynecology and Perinatology, Moscow

Email: secretariat@oparina4.ru
academician of RAMN, director of V.I. Kulakov RI for Obstetrics, Gynecology and Perinatology Россия

A. I. Shchegolev

V.I. Kulakov Research Centre for Obstetrics, Gynecology and Perinatology, Moscow

Email: ashegolev@oparina4.ru

PhD, professor, Head of the 2nd Pathology Department of V.I. Kulakov RI for Obstetrics, Gynecology and Perinatology

 

 

Россия

References

  1. Ramon y Cajal S. Sur les ganglions et plexus nerveux de l’intestin. CR Soc. Biol. (Paris). 1893; 45: 217–23.
  2. Faussone Pellegrini M.S., Cortesini C., Romagnoli P. Ultrastructure of the tunica muscularis of the cardial portion of the human esophagus and stomach, with special reference to the so-called Cajal’s interstitial cells. Arch. Ital. Anat. Embriol. 1977; 82 (2): 157–177.
  3. Thuneberg L. Interstitial cells of Cajal: intestinal pacemaker cells? Adv Anat Embryol Cell Biol. 1982; 71: 1–130.
  4. Hanani M., Freund H.R. Interstitial cells of Cajal — their role in pacing and signal transmission in the digestive system. Acta Physiol. Scand. 2000; 170 (3): 177–190.
  5. Komuro T., Seki K., Horiguchi K. Ultrastructural characterization of the interstitial cells of Cajal. Arch. Histol. Cytol. 1999; 62 (4): 295–316.
  6. Radenkovic G., Savic V., Mitic D., Grahovac S., Bjelakovic M., Krs-tic M. Development of c-kit immunopositive interstitial cells of Cajal in the human stomach. J. Cell. Mol. Med. 2010; 14 (5): 1125–1134.
  7. Metzger R., Schuster T., Till H., Franke F.E, Dietz H.G. Cajal-like cells in the upper urinary tract: comparative study in various species. Pediatr. Surg. Int. 2005; 21 (3): 169–174.
  8. Van der Aa F., Roskams T., Blyweert W., De Ridder D. Interstitial cells in the human prostate: a new therapeutic target? Prostate. 2003; 56 (4): 250–255.
  9. Rusu M.C., Pop F., Hostiuc S., Curcă G.C., Streinu-Cercel A. Extrahepatic and intra hepatic human portal interstitial Cajal cells. Anat Rec (Hoboken). 2011; 294 (8): 1382–1392.
  10. Hinescu M.E., Ardeleanu C., Gherghiceanu M., Popescu L.M. Interstitial Cajal-like cells in human gallbladder. J. Mol. Histol. 2007; 38: 275–284.
  11. Pasternak A., Gajda M., Gil K., Matyja A., Tomaszewski K.A., Walocha J.A. et al. Evidence of interstitial Cajal-like cells in human gallbladder. Folia Histochem. Cytobiol. 2012; 50 (4): 581–585.
  12. Wang X.Y., Diamant N.E., Huizinga J.D. Interstitial cells of Cajal: pacemaker cells of the pancreatic duct? Pancreas. 2011; 40 (1): 137–143.
  13. Hinescu M.E., Popescu L.M., Gherghiceanu M., Faussone-Pellegrini M.S. Interstitial Cajal-like cells in rat mesentery: an ultrastructural and immunohistochemical approach. J. Cell Mol. Med. 2008; 12 (1): 260–270.
  14. Pucovský V.1., Harhun M.I., Povstyan O.V., Gordienko D.V., Moss R.F., Bolton T.B. Close relation of arterial ICC-like cells to the contractile phenotype of vascular smooth muscle cell. J. Cell Mol. Med. 2007; 11 (4): 764–775.
  15. Hinescu M.E., Popescu L.M. Interstitial Cajal-like cells (ICLC) in human atrial myocardium. J. Cell Mol. Med. 2005; 9 (4): 972–975.
  16. McCloskey K.D., Hollywood M.A., Thornbury K.D. Ward S.M., McHale N.G. Kit-like immunopositive cells in sheep mesenteric lymphatic vessels. Cell Tissue Res. 2002; 310 (1): 77–84.
  17. Cretoiu S.M., Cretoiu D., Suciu L., Popescu L.M. Interstitial Cajal-like cells of human Fallopian tube express estrogen and progesterone receptors. J. Mol. Histol. 2009; 40 (5–6): 387–394.
  18. Popescu L.M., Ciontea S.M., Cretoiu D. Interstitial Cajal-like cells in human uterus and fallopian tube. Ann. NY Acad. Sci. 2007; 1101: 139–165.
  19. Duquette R.A., Shmygol A., Vaillant C., Mobasheri A., Pope M., Burdyga T. et al. Vimentin-positive, c-kit-negative interstitial cells in human and rat uterus: a role in pacemaking? Biol. Reprod. 2005; 72 (2): 276–283.
  20. Hutchings G., Williams O., Cretoiu D., Ciontea S.M. Myometrial interstitial cells and the coordination of myometrial contractility. J. Cell Mol. Med. 2009; 13 (10): 4268–4282.
  21. Gherghiceanu M., Popescu L.M. Interstitial Cajal-like cells (ICLC) in human resting mammary gland stroma. Transmission electron microscope (TEM) identification. J. Cell Mol. Med. 2005; 9 (4): 893–910.
  22. Suciu L., Popescu L.M, Gherghiceanu M. Human placenta: de visu demonstration of interstitial Cajal-like cells. J. Cell Mol. Med. 2007; 11 (3): 590–597.
  23. Komuro T. Structure and organization of interstitial cells of Cajal in the gastrointestinal tract. J. Physiol. 2006; 576 (3): 653–658.
  24. Kurahashi M., Zheng H., Dwyer L., Ward S.M., Don Koh S., Sanders K.M. A functional role for the «fibroblast-like cells» in gastrointestinal smooth muscles. Physiol. 2011; 589 (Pt 3): 697–710.
  25. Yin J., Chen J.D. Roles of interstitial cells of Cajal in regulating gastrointestinal motility: in vitro versus in vivo studies. J. Cell. Mol. Med. 2008; 12 (4): 1118–1129.
  26. Popescu L.M., Faussone-Pellegrini M.S. Telocytes — a case of serendipity: the winding way from Interstitial cells of Cajal (ICC), via interstitial Cajal-Like Cells (ICLC) to telocytes. J. Cell Mol. Med. 2010; 14 (4): 729–740.
  27. Международные термины по цитологии и гистологии человека с официальным списком русских эквивалентов. Под ред. В.В. Банина, В.Л. Быкова. М.: ГЭОТАР-Медиа. 2009. 272 с.
  28. Wu J.J., Rothman T.P., Gershon M.D. Development of the Interstitial Cell of Cajal: Origin, Kit Dependence and Neuronal and Nonneuronal Sources of Kit Ligand. J. Neurosci. Res. 2000; 59 (3): 384–401.
  29. Ward S.M., Ordög T., Bayguinov J.R., Horowitz B., Epperson A., Shen L. et al. Development of interstitial cells of Cajal and pacemaking in mice lacking enteric nerves. Gastroenterology. 1999; 117 (3): 584–594.
  30. Sanders K.M., Ordög T., Koh S.D., Torihashi S., Ward S.M. Development and plasticity of interstitial cells of Cajal. Neurogastroenterol. Motil. 1999; 11 (5): 311–338.
  31. Kluppel M., Huizinga J.D., Malysz J., Bernstein A. Developmental origin and Kit-dependent development of the interstitial cells of Cajal in the mammalian small intestine. Develop. Dyn. 1998; 211 (1): 60–71.
  32. Mei F., Han J., Huang Y. Jiang Z.Y., Xiong C.J., Zhou D.S. Plasticity of interstitial cells of Cajal: A study in the small intestine of adult Guinea pigs. Anat Rec (Hoboken). 2009; 292 (7): 985–993.
  33. Hinescu M.E., Gherghiceanu M., Suciu L., Popescu L.M. Telocytes in pleura: two- and three-dimensional imaging by transmission electron microscopy. Cell Tissue Res. 2011; 343 (2): 389–397.
  34. Mikkelsen H.B. Interstitial cells of Cajal, macrophages and mast cells in the gut musculature: morphology, distribution, spatial and possible functional interactions. J. Cell. Mol. Med. 2010; 14 (4): 818–832.
  35. Popescu L.M., Gherghiceanu M., Cretoiu D., Radu E. The connective connection: interstitial cells of Cajal (ICC) and ICC-like cells establish synapses with immunoreactive cells. Electron microscope study in situ. J. Cell Mol. Med. 2005; 9 (3): 714–730.
  36. Ye J., Zhu Y., Waliul I., Khan W.I.,Van Snick J., Huizinga J.D. IL-9 enhances growth of ICC, maintains network structure and strengthens rhythmicity of contraction in culture. J. Cell. Mol. Med. 2006; 10 (3): 687–694.
  37. Popescu L.M., Nicolescu M.I. Resident Stem Cells and Regenerative Therapy. In: Telocytes and Stem Cells. Chapter 11. R. Coeli, S. Goldenberg, А. Campos, С. de Carvalho (eds.). New York: Elsevier. 2013. 270 р.
  38. Epperson A, Hatton W.J., Callaghan B., Doherty P., Walker R.L., Sanders K.M. et al. Molecular markers expressed in cultured and freshly isolated interstitial cells of Cajal. Am. J. Physiol. Cell Physiol. 2000; 279 (2): 529–539.
  39. Saotome T., Inoue H., Fujiyama M., Fujiyama Y., Bamba T. Morphological and immunocytochemical identification of periacinar fibroblast-like cells derived from human pancreatic acini. Pancreas. 1997; 4 (4): 373–382.
  40. Hutchings G., Gevaert T., Depres J., Roskams T., Van Lommel A., Nilius B. et al. Research Immunohistochemistry using an antibody to unphosphorylated connexin 43 to identify human myometrial interstitial cells. Reprod. Biol. Endocrinol. 2008; 16 (6): 43.
  41. Farrugia G., Szurszewski J.H. Heme oxygenase, carbon monoxide, and interstitial cells of Cajal. Microsc. Res. Tech. 47 (5): 321–447.
  42. Hutchings G., Deprest J., Nilius B., Roskams T., De Ridder D. The effect of imatinib mesylate on the contractility of isolated rabbit myometrial strips. Gynecol. Obstet. Invest. 2006; 62: 79–83.
  43. Popescu L.M., Vidulescu C., Curici A., Caravia L., Simiones-cu A.A., Ciontea S.M. et al. Imatinib inhibits spontaneous rhythmic contractions of human uterus and intestine. Eur. J. Pharmacol. 2006; 546: 177–181.
  44. Koh S.D., Jun J.Y., Kim T.W., Sanders K.M. A Ca (2+)-inhibited non-selective cation conductance contributes to pacemaker currents in mouse interstitial cell of Cajal. J. Physiol. 2002; 540 (3): 803–814.
  45. Воротников А.В., Щербаков О.В., Кудряшова Т.В., Тарасова О.С., Ширинский В.П., Г.П. Фитцер и др. Фосфорилирование миозина как основной путь сокращения гладких мышц. Росс. физиол. журн. им. И.М. Сеченова. 2009; 95 (10): 1058–1073.
  46. van Gestel I., IJland M.M., Hoogland H.J., Evers J.L. Endome-trial wave-like activity in the non-pregnant uterus. Hum. Reprod. 2003; 9 (2): 131–138.
  47. Bulletti С., de Ziegler D. Uterine contractility and embryo implantation. Curr. Opin. Obstet. Gynecol. 2006; 18 (4): 473–484.
  48. Cretoiu S.M., Cretoiu D., Marin A., Radu B.M., Popescu L.M. Telocytes: ultrastructural, immunohistochemical and electrophysiological characteristics in human myometrium. Reproduction. 2013; 145 (4): 357–370.
  49. Rosenbaum S.T., Svalø J., Nielsen K., Larsen T., Jørgensen J.C., Bouchelouche P. Immunolocalization and expresson of small-conductance calcium activated potassium channels in human myometrium. J. Cell Mol. Med. 2012; 16 (12): 3001–3008.
  50. Becheanui G., Manu M., Dumbravă M., Herlea V., Hortopan M., Costache M. The evaluation of interstitial Cajal cellsdistribution in non-tumoral colondisorders. Rom. J. Morphol. Embryol. 2008; 49 (3): 351–355.
  51. Wang X.Y., Zarate N., Soderholm J.D., Bourgeois J.M., Liu L.W., Huizinga J.D. Ultrastructural injury to interstitial cells of Cajal and communication with mast cells in Crohn’s disease. Neurogastroenterol Motil. 2007; 19 (5): 349–349.
  52. Agaimy A. Wünsch P.H. Sporadic Cajal cell hyperplasia is common in resection specimens for distal oesophageal carcinoma. A retrospective review of 77 consecutive surgical resection specimens. Virchov Arch. 2006; 448 (3): 288–294.
  53. WHO classification of tumours of the digestive system. F.T. Bos-man, F. Carneiro, R.H.Hruban et al. (eds.). Lyon.: International Agency for Research on Cancer. 2010. 417 p.
  54. Дубова Е.А., Щеголев А.И., Мишнев О.Д., Кармазановский Г.Г. Гастроинтестинальные стромальные опухоли. Медицинская визуализация. 2007; 1: 25–31.
  55. Miettinen M., Fletcher C.D.M., Kindblom L.-G., Tsui W.M.S. et al. Mesenchimal tumors of the small intestine. WHO classification of tumours of the digestive system. F.T. Bosman, F. Carneiro, R.H. Hruban et al. (eds.). Lyon: International Agency for Research on Cancer. 2010. P. 115–118.
  56. Щеголев А.И., Дубова Е.А., Мишнев О.Д., Егоров В.И., Кармазановский Г.Г. Гастроинтестинальные стромальные опухоли. М. 2007. 32 с.
  57. Zhao X., Yue C. Gastrointestinal stromal tumor. J. Gastrointest. Oncol. 2012; 3 (3): 189–208.
  58. Казанцева И.А., Гуревич Л.Е., Бобров М.А. Патоморфологическая диагностика гастроинтестинальных стромальных опухолей. М. 2013. 71 с.
  59. Дубова Е.А., Щеголев А.И., Егоров В.И., Мишнев О.Д. Гастроинтестинальные стромальные опухоли тонкой кишки. Росс. мед. журн. 2008; 2: 22–24.
  60. Lamba G., Gupta R., Lee B., Ambrale S., Liu D. Current management and prognostic features for gastrointestinal stromal tumor (GIST). Exp. Hematol. Oncol. 2012; 1 (1): 14.
  61. Егоров В.И., Кармазановский Г.Г., Щеголев А.И., Дубова Е.А., Яшина Н.И., Осипова Н.Ю. и др. Значение предоперационной визуализации для выбора хирургической тактики при гастроинтестинальных стромальных опухолях. Медицинская визуализация. 2007; 2: 34–43.
  62. Rammohan A., Sathyanesan J., Rajendran K. A gist of gastrointestinal stromal tumors: A review. World J. Gastrointest. Oncol. 2013; 5 (6): 102–112.
  63. Beham A.W., Schaefer I.M., Schüler P. Gastrointestinal stromal tumors. Int. J. Colorect. Dis. 2012; 27 (6): 689–700.
  64. Heinrich M.C., Corless C.L., Demetri G.D., Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J. Clin. Oncol. 2003; 21 (23): 4342–4349.
  65. Fletcher C.D., Berman G.G., Corless C., Gorstein F., Lasota J., Longley B.J. et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum. Pathol. 2002; 33 (5): 459–465.
  66. Kindblom L.G., Remotti H.E., Aldenborg F., Meis-Kindblom J.M. Gastrointestinal pacemaker cell tumor (GIPACT) gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am. J. Pathol. 1998; 152 (5): 1259–1269.
  67. Tazawa K., Tsukada K., Makuuchi H. An immunohistochemical and clinicopathological study of gastrointestinal stromal tumors. Pathol. Int. 1999; 49 (9): 786–798.
  68. Terada T. Gastrointestinal stromal tumor of the uterus: A case report with genetic analyses of c-kit and PDGFR A genes. Int. J. Gynecol. Pathol. 2009; 28 (1): 29–34.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 1970 "Paediatrician" Publishers LLC



This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies