History Of The Stromal Cells: From Interstitial Cajal Cells To Telocytes - A Brief Overview Of The Human Telocytes And Their Possible Functions

Merjem Purelku; Gamze Tanrıverdi

doi:10.19161/etd.1308902

EN TR

History Of The Stromal Cells: From Interstitial Cajal Cells To Telocytes - A Brief Overview Of The Human Telocytes And Their Possible Functions

Abstract

In the organ microenvironment stromal cells make up an essential population, however research on them has been very limited. The stroma mainly consists of fibroblasts that reside together with mesenchymal cells, endothelial cells, pericytes, neurons, adipocytes, immune cells etc. The different morphologies and functional properties of stromal cells have led to subclassification of different cell types in connective tissue. Among them are the interstitial cells of Cajal and telocytes. Telocytes are one of the newer cells known for their small cell bodies and long telopods and have been recently identified in the connective tissue of many organs. Telocytes are strategically positioned near nerve endings, around blood capillaries and in close relation with particular cells. The network of telocytes is engaged in integrating information from multiple sources and coordinating the tissue homeostasis in response to the tissues local functional requirements. Extracellular vesicles provide a means of bidirectional communication, and their secretome appears to control the mechanisms of stem cell differentiation. Telocytes have been identified in various organs, specifically in human heart, lungs, brain, eye, thyroid, skeletal muscles, skin, salivary glands, gastrointestinal tract, pancreas, gallbladder, liver, and organs of the male and female urogenital system. Additionally, given the heterogeneity of the organs in which telocytes are found, and their capability to play a role in the etiopathogenesis of various diseases, the concept of "telocytopathies" has emerged. In conclusion, telocytes are increasingly becoming a focal point for the understanding of idiopathic diseases that affect humans as well as the development of new diagnostic and therapeutic approaches, and they have the potential to contribute to regenerative medicine.

Keywords

Stromal Hücrelerin Tarihçesi: İnterstisyel Cajal Hücrelerinden Telositlere - İnsan Telositlerine ve Olası İşlevlerine Kısa Bir Bakış

Öz

Stromal hücreler, birçok organda özelleşmiş mikro ortamların yaratılmasında önemli bir rol oynamasına rağmen bunlarla ilgili yapılan araştırmalar oldukça kısıtlı olmuştur. Stroma esas olarak fibroblastlar, mezenkimal hücreler, endotel hücreleri, perisitler, nöronlar, adipositler ve immün hücrelerden oluşur. Stromal hücrelerin değişik morfolojiler ve işlevsel özelliklere sahip olmaları, bağ dokusunda farklı hücre türlerinin alt sınıflanmasına sebep olmuştur. Bunların arasında Cajal'ın interstisyel hücreleri ve telositler de yer alır. Telositler, küçük hücre gövdeleri ve uzun telopodları ile bilinen ve yakın zamanda birçok organın bağ dokusunda tanımlanmış olan yeni hücrelerden biridir. Telositler, sinir uçlarının ve kılcal damarların yakınında olarak, belirli hedef hücreler arasında, oldukça stratejik bir konumdadırlar. Telositlerin görevi, birden fazla kaynaktan gelen farklı bilgileri entegre etme ve dokuların yerel fonksiyonel gereksinimlerine yanıt olarak doku homeostazını koordine etmektir. Hücre dışı vezikülleri, çift yönlü bir iletişim sağlarken, sekretomlarının, kök hücrelerin farklılaşma mekanizmalarını düzenlediği görülmektedir. Telositler aynı zamanda, insan kalbi, akciğer, beyin, göz, tiroid, iskelet kasları, deri, tükürük bezleri, gastrointestinal kanal, pankreas, safra kesesi, karaciğer, ve erkek ve dişi ürogenital sistemlerinde olduğu gibi birçok organda tanımlanmıştır. Buna ek olarak, telositlerin bulunduğu organların heterojenliği göz önüne alındığında, ve çeşitli hastalıkların etiyopatogenezinde rol oynayabilme kabiliyetleri, "telositopatiler" tanımını ortaya çıkarmıştır. Sonuç olarak, telositler, özellikle insanları etkileyen idiyopatik hastalıkların anlaşılmasında, yeni teşhis ve tedavi yaklaşımlarının geliştirilmesinde giderek odak noktası olmaktadırlar ve rejeneratif tıbba katkı sağlayabilme potansiyeline de sahiptirler.

Anahtar Kelimeler

Kaynakça

1. Rohira AD, Lonard DM, Biology C. Emerging roles of steroid receptor coactivators in stromal cell responses. 2022;248(2):1–16.
2. Hauser AE. Stromazellen als Koordinatoren für die adaptive Immunantwort und das immunologische Gedächtnis. Z Rheumatol. 2013;72(10):986–92.
3. Vickaryous MK, Hall BK. Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest. Biol Rev Camb Philos Soc. 2006;81(3):425–55.
4. Popescu LM, Gherghiceanu M, Suciu LC, Manole CG, Hinescu ME. Telocytes and putative stem cells in the lungs: Electron microscopy, electron tomography and laser scanning microscopy. Cell Tissue Res. 2011;345(3):391–403. 5. Gauthier V, Kyriazi M, Nefla M, Pucino V, Raza K, Buckley CD, et al. Fibroblast heterogeneity: Keystone of tissue homeostasis and pathology in inflammation and ageing. Front Immunol. 2023;14(2):1–15.
6. Singh AJ, Gray JW. Chemokine signaling in cancer-stroma communications. J Cell Commun Signal. 2021;15(3):361–81.
7. Hinescu ME, Gherghiceanu M, Suciu L, Popescu LM. Telocytes in pleura: Two- and three-dimensional imaging by transmission electron microscopy. Cell Tissue Res. 2011;343(2):389–97.
8. Popescu LM, Faussone-Pellegrini MS. 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):729–40.
9. Ceafalan L, Gherghiceanu M, Popescu LM, Simionescu O. Telocytes in human skin - are they involved in skin regeneration? J Cell Mol Med. 2012;16(7):1405–20.

10. Aleksandrovych V, Sajewicz M, Walocha JA, Gil K. Tubal telocytes: factor infertility reason? Folia Med Cracov. 2016;56(2):17–23.
11. Vannucchi MG. The telocytes: Ten years after their introduction in the scientific literature. an update on their morphology, distribution, and potential roles in the gut. Int J Mol Sci. 2020;21(12):1–15.
12. Cretoiu SM, Popescu LM, Access O. Telocytes revisited Introduction : identification and. 2014;5(5):353–69.
13. Klein M, Csöbönyeiová M, Danišovič Ľ, Lapides L, Varga I. Telocytes in the Female Reproductive System : Up-to-Date Knowledge , Challenges and Possible Clinical Applications. Life. 2022;12(2):1–13.
14. Klein M, Lapides L, Fecmanova D, Varga I. From Telocytes to Telocytopathies . Do Recently Described Interstitial Cells Play a Role in Female Idiopathic Infertility ? Med. 2020;56(12):688.
15. Cretoiu D, Babes V. Human cardiac telocytes : 3D imaging by FIB-SEM tomography. 2014;18(11):2157–64.
16. Rusu MC, Hostiuc FPS, Curca GC, Jianu AM, Paduraru D. Telocytes form networks in normal cardiac tissues. Histol Histopathol. 2012;27(6):807–16.
17. Rigoriu FLG, Ostiuc SOH, Rapciu ALDI V. Subsets of telocytes : the progenitor cells in the human endocardial niche. Rom J Morphol Embryol. 2016;57(2):767–74.
18. Mitrofanova LB, Gorshkov AN, Konovalov P V, Krylova JS. Telocytes in the human sinoatrial node. 2018;22(1):521–32.
19. Yang Y, Wu SM, Xiao J. Telocytes in human heart valves. 2014;18(5):759–65.
20. Mandache E, Gherghiceanu M, Macarie C, Kostin S, Popescu LM. Telocytes in human isolated atrial amyloidosis : ultrastructural remodelling. 2010;14(12):2739–47.
21. Sukhacheva T V, Nizyaeva N V, Samsonova M V, Cherniaev AL, Burov AA, Iurova M V, et al. Morpho ‑ functional changes of cardiac telocytes in isolated atrial amyloidosis in patients with atrial fibrillation. Sci Rep. 2021;11(1):1–19.
22. Sukhacheva T V, Nizyaeva N V, Samsonova M V, Chernyaev AL, Shchegolev AI, Serov RA. Telocytes in the Myocardium of Children with Congenital Heart Disease Tetralogy of Fallot. 2020;(1):137–46.
23. Richter M, Kostin S. The failing human heart is characterized by decreased numbers of telocytes as result of apoptosis and altered extracellular matrix composition. 2015;19(11):2597–606.
24. Varga I, Urban L, Kajanová M, Polák Š. Functional histology and possible clinical significance of recently discovered telocytes inside the female reproductive system. Arch Gynecol Obstet. 2016;294(2):417–22.
25. Aschacher T, Schmidt K, Aschacher O, Eichmair E, Baranyi U, Winkler B, et al. Telocytes in the human ascending aorta: Characterization and exosome-related KLF-4/VEGF-A expression. J Cell Mol Med. 2021;25(20):9697–709.
26. Aschacher T, Aschacher O, Schmidt K, Enzmann FK, Eichmair E, Winkler B, et al. The Role of Telocytes and Telocyte-Derived Exosomes in the Development of Thoracic Aortic Aneurysm. Int J Mol Sci. 2022;23(9):4730.
27. Bhargav D. Sanketi, Madhav Mantri MAT, Hu S, Z. MF, Wang, , Iwijn De Vlaminck2 NAK. Spatiotemporal reconstruction of the origin and assembly of smooth muscles in the intestinal villus. bioRxiv. 2023;Preprint.
28. Rosa I, Marini M, Guasti D, Ibba-Manneschi L, Manetti M. Morphological evidence of telocytes in human synovium. Sci Rep. 2018;8(1):1–10.
29. Manetti M, Rosa I, Messerini L, Guiducci S, Matucci-cerinic M, Ibba-manneschi L. A loss of telocytes accompanies fibrosis of multiple organs in systemic sclerosis. 2014;18(2):253–62.
30. Vannucchi M, Traini C, Manetti M, Ibba-manneschi L. Telocytes express PDGFR a in the human gastrointestinal tract. 2013;17(9):1099–108.
31. Franca A, Ruffo M, Manetti M, Rosa I, Conte D, Fazi M, et al. Telocytes in Crohn ’ s disease. 2013;17(12):1525–36 . 32. Manetti M, Rosa I, Messerini L, Ibba-manneschi L. Telocytes are reduced during fibrotic remodelling of the colonic wall in ulcerative colitis. 2015;19(1):62–73.
33. Smith M, Chhabra S, Shukla R, Kenny S, Almond S, Edgar D, et al. The transition zone in Hirschsprung ’ s bowel contains abnormal hybrid ganglia with characteristics of extrinsic nerves. J Cell Mol Med. 2023;27(2):287–98.
34. Rusu MC, Pop F, Hostiuc S, Curca GC, Cytobiology A. Extrahepatic and Intrahepatic Human Portal Interstitial Cajal Cells. Anat Rec. 2011;294(8):1382–92.
35. Fu S. Telocytes in human liver fibrosis. 2015;19(3):676–83.
36. Padhi S, Nayak HK. Primary Extragastrointestinal Stromal Tumours in the Hepatobiliary Tree and Telocytes. Adv Exp Med Biol. 2016;913:207–28.
37. Matyja A, Gil K, Pasternak A, Sztefko K, Gajda M. Telocytes : new insight into the pathogenesis of gallstone disease. 2013;17(6):734–42.
38. Mihnea I. Nicolescu, MD, DMD and Laurentiu M. Popescu, MD P. Telocytes in the Interstitium of Human Exocrine Pancreas. 2012;41(6):949–56.
39. Nicolescu MI, Bucur A, Dinca O, Rusu MC, Popescu LM. Telocytes in Parotid Glands. 2012;385(August 2011):378–85.
40. Alunno A, Ibba-manneschi L, Bistoni O, Rosa I, Caterbi S, Gerli R, et al. Telocytes in minor salivary glands of € gren ’ s syndrome : association with the extent of primary Sj o inflammation and ectopic lymphoid neogenesis. 2015;19(7):1689–96.
41. Rosa I, Ibba-Manneschi L, Guasti D, Perigli G, Faussone-Pellegrini MS, Manetti M. Morphologic evidence of telocytes in human thyroid stromal tissue. J Cell Mol Med. 2022;26(8):2477–81.
42. Bojin FM, Gavriliuc OI, Cristea MI, Tanasie G, Tatu CS, Panaitescu C, et al. Telocytes within human skeletal muscle stem cell niche. J Cell Mol Med. 2011 Oct;15(10):2269–72.
43. Marini M, Manetti M, Rosa I, Ibba-Manneschi L, Sgambati E. Telocytes in human fetal skeletal muscle interstitium during early myogenesis. Acta Histochem. 2018;120(5):397–404.
44. Rotoli D, Cejas MM, Maeso M del C, Pérez-Rodríguez ND, Morales M, Ávila J, et al. The Na, K-ATPase β-subunit isoforms expression in glioblastoma multiforme: Moonlighting roles. Int J Mol Sci. 2017;18(11):2369.
45. Mitrofanova L, Hazratov A, Galkovsky B, Gorshkov A, Bobkov D, Gulyaev D, et al. Morphological and immunophenotypic characterization of perivascular interstitial cells in human glioma: Telocytes, pericytes, and mixed immunophenotypes. Oncotarget. 2020;11(4):322–46.
46. Nicolescu MI, Rusu MC, Voinea LM, Vrapciu AD, Bâră RI. Lymphatic lacunae of the human eye conjunctiva embedded within a stroma containing CD34+ telocytes. J Cell Mol Med. 2020;24(15):8871–5.
47. Petrea CE, Crăiţoiu, Vrapciu AD, Mănoiu VS, Rusu MC. The telopode- and filopode-projecting heterogeneous stromal cells of the human sclera niche. Ann Anat. 2018;218(Jul):129–40.
48. Marini M, Mencucci R, Rosa I, Favuzza E, Guasti D, Ibba-Manneschi L, et al. Telocytes in normal and keratoconic human cornea: an immunohistochemical and transmission electron microscopy study. J Cell Mol Med. 2017;21(12):3602.
49. Semiz F, Lokaj AS, Tanriverdi G, Caliskan G, Hima-Musa N, Semiz CE. Fresh Human Myopic Lenticule Intrastromal Implantation for Keratoconus Using SMILE Surgery in a Long-term Follow-up Study: Ultrastructural Analysis by Transmission Electron Microscopy. J Refract Surg. 2022;38(8):520–8.
50. Rusu MC, Mirancea N, Mǎnoiu VS, Vâlcu M, Nicolescu MI, Pǎduraru D. Skin telocytes. Ann Anat. 2012;194(4):359–67.
51. Cretoiu D, Gherghiceanu M, Hummel E, Zimmermann H, Simionescu O, Popescu LM. FIB-SEM tomography of human skin telocytes and their extracellular vesicles. J Cell Mol Med. 2015;19(4):714–22.
52. Manole CG, Gherghiceanu M, Simionescu O. Telocyte dynamics in psoriasis. J Cell Mol Med. 2015;19(7):1504–19.
53. Mirancea N, Moroşanu AM, Mirancea G V., Juravle FD, Mǎnoiu VS. Infrastructure of the telocytes from tumor stroma in the skin basal and squamous cell carcinomas. Rom J Morphol Embryol. 2013;54(4):1025–37.
54. Rusu MC, Mogoantă L, Pop F, Dobra MA. Molecular phenotypes of the human kidney: Myoid stromal cells/telocytes and myoepithelial cells. Ann Anat. 2018;218(Jul):95–104.
55. Farris AB, Ellis CL, Rogers TE, Lawson D, Cohen C, Rosen S. Renal medullary and cortical correlates in fibrosis, epithelial mass, microvascularity, and microanatomy using whole slide image analysis morphometry. PLoS One. 2016;11(8):1–18.
56. Dobra MA, Vrapciu AD, Pop F, Petre N, Rusu MC. Acta Histochemica The molecular phenotypes of ureteral telocytes are layer-speci fi c. Acta Histochem. 2018;120(1):41–5.
57. Gevaert T, Vos R De, Aa F Van Der, Joniau S, Oord J Van Den, Roskams T, et al. Identification of telocytes in the upper lamina propria of the human urinary tract. 2012;16(9):2085–93.
58. Wolnicki M, Aleksandrovych V, Gil A. Relation between ureteral telocytes and the hydronephrosis development in children. Folia Med Cracov. 2019;59(3):31–44.
59. Wishahi M, Hafiz E, Wishahy AMK, Badawy M. Telocytes , c-Kit positive cells , Smooth muscles , and collagen in the ureter of pediatric patients with congenital primary obstructive megaureter : elucidation of etiopathology. Ultrastruct Pathol. 2021;45(3):257–65.
60. Vannucchi MG, Traini C, Guasti D, Giulio DP, Faussone-Pellegrini MS. Telocytes subtypes in human urinary bladder. J Cell Mol Med. 2014;18(10):2000–8.
61. Wishahi M, Hassan S, Hassan M, Badawy M, Hafiz E. Telocytes and ezrin expression in normal ‑ appearing tissues adjacent to urothelial bladder carcinoma as predictors of invasiveness and recurrence. Sci Rep. 2023;13(1):6179.
62. Cretoiu SM, Simionescu AA, Caravia L, Curici A, Cretoiu D, Popescu LM. Complex effects of imatinib on spontaneous and oxytocin-induced contractions in human non-pregnant myometrium. 2011;98(3):329–38.
63. Hatta K, Huang M, Weisel RD. Culture of rat endometrial telocytes Human tissue collection. 2012;16(7):1392–6.
64. Othman ER, Elgamal DA, Refaiy AM, Abdelaal II, Abdel-mola AF. Identification and potential role of telocytes in human uterine leiomyoma. Contracept Reprod Med. 2016;20(Jul):12.
65. Aleksandrovych V, Bereza T, Ulatowska-białas M, Pasternak A, Walocha JA, Pityński K, et al. Identification of PDGFR α + cells in uterine fibroids – link between angiogenesis and uterine telocytes. Arch Med Sci. 2022;18(5):1329–37.
66. Aleksandrovych V. Retrospective analysis of a case report of a left ovarian ectopic pregnancy after the former tubal. Folia Med Cracov. 2022;62(4):121–35.
67. Karasu Y, Önal D, Zirh S, Yersal N, Korkmaz H, Üstün Y, et al. Role of telocytes in the pathogenesis of ectopic pregnancy. Eur Rev Med Pharmacol Sci. 2022;26(1):110–9.
68. Nizyaeva N V, Sukhacheva T V, Kulikova G V, Nagovitsyna MN, Poltavtseva RA, Kan NE, et al. Ultrastructural Characteristics of Placental Telocytes. 2017;162(11):693–8.
69. Bosco C, Díaz E, Gutiérrez R, González J, Rodrigo R, Barja P. A putative role for telocytes in placental barrier impairment during. Med Hypotheses. 2015;84(1):72–7.
70. Petre N, Rusu MC, Pop F, Jianu AM. Telocytes of the mammary gland stroma. Folia Morphol (Warsz). 2016;75(2):224–31.
71. Mihalcea CE, Moroşanu AM, Murăraşu D, Puiu L, Cinca SA, Voinea SC, et al. Analysis of TP53 gene and particular infrastructural alterations in invasive ductal mammary carcinoma. Rom J Morphol Embryol. 2020;61(2):441–7.
72. Marini M, Rosa I, Guasti D, Gacci M, Sgambati E, Ibba- L, et al. Reappraising the microscopic anatomy of human testis : identification of telocyte networks in the peritubular and intertubular stromal space. Sci Rep. 2018;8(1):14780.
73. Marini M, Ibba-Manneschi L, Rosa I, Sgambati E, Manetti M. Changes in the telocyte/CD34+ stromal cell and α-SMA+ myoid cell networks in human testicular seminoma. Acta Histochem. 2019;121(8):151442.

Ayrıntılar

Birincil Dil

İngilizce

Konular

Histoloji ve Embriyoloji , Sağlık Kurumları Yönetimi

Bölüm

Derleme

Yazarlar

Merjem Purelku ^*
0000-0003-2219-0231
Türkiye

Gamze Tanrıverdi
0000-0002-8646-0336
Türkiye

Yayımlanma Tarihi

18 Aralık 2023

Gönderilme Tarihi

9 Haziran 2023

Kabul Tarihi

14 Temmuz 2023

Yayımlandığı Sayı

Yıl 2023 Cilt: 62 Sayı: 4

DOI

https://doi.org/10.19161/etd.1308902

IZ

https://izlik.org/JA43LY79RN

Kaynak Göster

RIS / Bibtex

Vancouver

1.Merjem Purelku, Gamze Tanrıverdi. History Of The Stromal Cells: From Interstitial Cajal Cells To Telocytes - A Brief Overview Of The Human Telocytes And Their Possible Functions. ETD. 01 Aralık 2023;62(4):579-88. doi:10.19161/etd.1308902

Cited By

Distribution and morphologic characterization of telocytes in rat ovary and uterus: insights from ultrastructural and immunohistochemical analysis

Histochemistry and Cell Biology

https://doi.org/10.1007/s00418-024-02313-w

Telocytes: history, origin, identification, structure, distribution, and functions

Histochemistry and Cell Biology

https://doi.org/10.1007/s00418-025-02413-1