In the last few years, a new cell type – interstitial Cajal-like cell (ICLC) – has been described in digestive and extra-digestive organs. The name has recently been changed to telocytes (TC) and their typical thin, long processes have been named telopodes (TP). To support the hypothesis that TC may also be present in human placenta and add to the information already available, we provide evidence on the ultrastructure, immunophenotype, distribution, and interactions with the surrounding stromal cells of TC in the villous core of human term placenta. We used phase-contrast microscopy, light microscopy of semithin sections, transmission electron microscopy, immunohistochemistry, and immunofluorescence of tissue sections or cell cultures, following a pre-established diagnostic algorithm. Transmission electron microscopy showed cells resembling TC, most (∼76%) having 2–3 very thin, longprocesses (tens to hundreds of micrometers), with an uneven calibre(≤0.5 µm thick) and typical branching pattern. The dilations of processes accommodate caveolae, endoplasmic reticulum cisternae, and mitochondria. These TC have close contacts with perivascular SMC in stem villi. In situ, similar cells are positive for c-kit, CD34, vimentin, caveolin-1, vascular endothelial growth factor (VEGF), and inducible nitric oxide synathase (iNOS). The c-kit-positive cells inconsistently co-express CD34, CD44, αSMA, S100, neuron-specific enolase, and nestin. Among cells with a morphologic TC profile in cell cultures, about 13% co-express c-kit, vimentin, and caveolin-1; 70% of the c-kit-positive cells co-express CD34 and 12% co-express iNOS or VEGF. In conclusion, this study confirms the presence of TC in human term placenta and provides their ultrastructural and immunophenotypic characterization.

1.
Alon, T., I. Hemo, A. Itin, J. Pe’er, J. Stone, E. Keshet (1995) Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1: 1024–1028.
2.
Benirschke, K., P. Kaufmann, R. Baergen (2006) Pathology of the Human Placenta. New York, Springer.
3.
Blondheim, N.R., Y.S. Levy, T. Ben-Zur, A. Burshtein, T. Cherlow, I. Kan, R. Barzilai, M. Bahat-Stromza, Y. Barhum, S. Bulvik, E. Melamed, D. Offen (2006) Human mesenchymal stem cells express neural genes, suggesting a neural predisposition. Stem Cells Dev 15: 141–164.
4.
Bussolati, G. (2005) Of GISTs and EGISTs, ICCs and ICs. Virchows Arch 447: 907–908.
5.
Camelliti, P., T.K. Borg, P. Kohl (2005) Structural and functional characterisation of cardiac fibroblasts. Cardiovasc Res 65: 40–51.
6.
Castellucci, M., P. Kaufmann (1982) A three-dimensional study of the normal human placental villous core. II. Stromal architecture. Placenta 3: 269–285.
7.
Ciontea, S.M., E. Radu, T. Regalia, L. Ceafalan, D. Cretoiu, M. Gherghiceanu, R.I. Braga, M. Malincenco, L. Zagrean, M.E. Hinescu, L.M. Popescu (2005) C-kit immunopositive interstitial cells (Cajal-type) in human myometrium. J Cell Mol Med 9: 407–420.
8.
Demir, R., N. Demir, G. Kohnen, G. Kosanke, A. Mironov, I. Uestuenel, E. Kocamaz (1992) Ultrastructure and distribution of myofibroblast-like cells in human placental stem villi. Electron Microscopy 3: 509–510.
9.
Demir, R., G. Kosanke, G. Kohnen, S. Kertschanska, P. Kaufmann (1997) Classification of human placental stem villi: review of structural and functional aspects. Microsc Res Tech 38: 29–41.
10.
Desforges, M., C.P. Sibley (2010) Placental nutrient supply and fetal growth. Int J Dev Biol 54: 377–390.
11.
Eyden, B. (2007) The myofibroblast: a study of normal, reactive and neoplastic tissues, with an emphasis on ultrastructure. J Submicrosc Cytol Pathol 7–166.
12.
Eyden, B. (2008) The myofibroblast: phenotypic characterization as a prerequisite to understanding its functions in translational medicine. J Cell Mol Med 12: 22–37.
13.
Farley, A.E., C.H. Graham, G.N. Smith (2004) Contractile properties of human placental anchoring villi. Am J Physiol Regul Integr Comp Physiol 287: R680–R685.
14.
Farrugia, G. (2008) Interstitial cells of Cajal in health and disease. Neurogastroenterol Motil 20(suppl 1): 54–63.
15.
Faussone-Pellegrini, M.S., L. Thuneberg (1999) Guide to the identification of interstitial cells of Cajal. Microsc Res Tech 47: 248–266.
16.
Feller, A.C., H. Schneider, D. Schmidt, M.R. Parwaresch (1985) Myofibroblast as a major cellular constituent of villous stroma in human placenta. Placenta 6: 405–415.
17.
Garcia-Lopez, P., V. Garcia-Marin, R. Martinez-Murillo, M. Freire (2009) Updating old ideas and recent advances regarding the Interstitial Cells of Cajal. Brain Res Rev 61: 154–169.
18.
Goldsmith, E.C., A. Hoffman, M.O. Morales, J.D. Potts, R.L. Price, A. McFadden, M. Rice, T.K. Borg (2004) Organization of fibroblasts in the heart. Dev Dyn 230: 787–794.
19.
Graf, R., J.U. Langer, G. Schonfelder, T. Oney, S. Hartel-Schenk, W. Reutter, H.H. Schmidt (1994) The extravascular contractile system in the human placenta: morphological and immunocytochemical investigations. Anat Embryol (Berl) 190: 541–548.
20.
Graf, R., G. Schonfelder, M. Muhlberger, M. Gutsmann (1995) The perivascular contractile sheath of human placental stem villi: its isolation and characterization. Placenta 16: 57–66.
21.
Hinescu, M.E., M. Gherghiceanu, E. Mandache, S.M. Ciontea, L.M. Popescu (2006) Interstitial Cajal-like cells (ICLC) in atrial myocardium: ultrastructural and immunohistochemical characterization. J Cell Mol Med 10: 243–257.
22.
Hinescu, M.E., L.M. Popescu, M. Gherghiceanu, M.S. Faussone-Pellegrini (2008) Interstitial Cajal-like cells in rat mesentery: an ultrastructural and immunohistochemical approach. J Cell Mol Med 12: 260–270.
23.
Huizinga, J.D., L. Thuneberg, J.M. Vanderwinden, J.J. Rumessen (1997) Interstitial cells of Cajal as targets for pharmacological intervention in gastrointestinal motor disorders. Trends Pharmacol Sci 18: 393–403.
24.
Hutchings, G., O. Williams, D. Cretoiu, S.M. Ciontea (2009) Myometrial interstitial cells and the coordination of myometrial contractility. J Cell Mol Med 13: 4268–4282.
25.
Junquera, C., C. Martinez-Ciriano, T. Castiella, P. Serrano, M.J. Azanza, S.R. Junquera (2007) Immunohistochemical and ultrastructural characteristics of interstitial cells of Cajal in the rabbit duodenum: presence of a single cilium. J Cell Mol Med 11: 776–787.
26.
Kauma, S., T. Huff, G. Krystal, J. Ryan, P. Takacs, T. Turner (1996) The expression of stem cell factor and its receptor, c-kit in human endometrium and placental tissues during pregnancy. J Clin Endocrinol Metab 81: 1261–1266.
27.
Keck, P.J., S.D. Hauser, G. Krivi, K. Sanzo, T. Warren, J. Feder, D.T. Connolly (1989) Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246: 1309–1312.
28.
Kohnen, G., S. Kertschanska, R. Demir, P. Kaufmann (1996) Placental villous stroma as a model system for myofibroblast differentiation. Histochem Cell Biol 105: 415–429.
29.
Kostin, S., L.M. Popescu (2009) A distinct type of cell in myocardium: interstitial Cajal-like cells (ICLCs). J Cell Mol Med 13: 295–308.
30.
Lammie, A., M. Drobnjak, W. Gerald, A. Saad, R. Cote, C. Cordon-Cardo (1994) Expression of c-kit and kit ligand proteins in normal human tissues. J Histochem Cytochem 42: 1417–1425.
31.
Leik, C.E., A. Willey, M.F. Graham, S.W. Walsh (2004) Isolation and culture of arterial smooth muscle cells from human placenta. Hypertension 43: 837–840.
32.
Lendahl, U., L.B. Zimmerman, R.D. McKay (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60: 585–595.
33.
Martinoli, C., M. Castellucci, D. Zaccheo, P. Kaufmann (1984) Scanning electron microscopy of stromal cells of human placental villi throughout pregnancy. Cell Tissue Res 235: 647–655.
34.
Marzioni, D., C. Crescimanno, D. Zaccheo, R. Coppari, C.B. Underhill, M. Castellucci (2001) Hyaluronate and CD44 expression patterns in the human placenta throughout pregnancy. Eur J Histochem 45: 131–140.
35.
McCloskey, K.D., A.M. Gurney (2002) Kit positive cells in the guinea pig bladder. J Urol 168: 832–836.
36.
Moncada, S., R.M. Palmer, E.A. Higgs (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43: 109–142.
37.
Pieri, L., M.G. Vannucchi, M.S. Faussone-Pellegrini (2008) Histochemical and ultrastructural characteristics of an interstitial cell type different from ICC and resident in the muscle coat of human gut. J Cell Mol Med 12: 1944–1955.
38.
Popescu, L.M., S.M. Ciontea, D. Cretoiu, M.E. Hinescu, E. Radu, N. Ionescu, M. Ceausu, M. Gherghiceanu, R.I. Braga, F. Vasilescu, L. Zagrean, C. Ardeleanu (2005a) Novel type of interstitial cell (Cajal-like) in human fallopian tube. J Cell Mol Med 9: 479–523.
39.
Popescu, L.M, M.S. Faussone-Pellegrini (2010) 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 14: 729–740.
40.
Popescu, L.M., M.E. Hinescu, N. Ionescu, S.M. Ciontea, D. Cretoiu, C. Ardelean (2005b) Interstitial cells of Cajal in pancreas. J Cell Mol Med 9: 169–190.
41.
Povstyan, O.V., D.V. Gordienko, M.I. Harhun, T.B. Bolton (2003) Identification of interstitial cells of Cajal in the rabbit portal vein. Cell Calcium 33: 223–239.
42.
Reilly, R.D., P.T. Russell (1977) Neurohistochemical evidence supporting an absence of adrenergic and cholinergic innervation in the human placenta and umbilical cord. Anat Rec 188: 277–286.
43.
Reynolds, L.P., P.P. Borowicz, J.S. Caton, K.A. Vonnahme, J.S. Luther, D.S. Buchanan, S.A. Hafez, A.T. Grazul-Bilska, D.A. Redmer (2010) Uteroplacental vascular development and placental function: an update. Int J Dev Biol 54: 355–366.
44.
Sanders, K.M., S.D. Koh, S.M. Ward (2006) Interstitial cells of cajal as pacemakers in the gastrointestinal tract. Annu Rev Physiol 68: 307–343.
45.
Sati, L., Y. Seval, A. Yasemin Demir, G. Kosanke, G. Kohnen, R. Demir (2007) Cellular diversity of human placental stem villi: an ultrastructural and immunohistochemical study. Acta Histochem 109: 468–479.
46.
Seval, Y., E.T. Korgun, R. Demir (2007) Hofbauer cells in early human placenta: possible implications in vasculogenesis and angiogenesis. Placenta 28: 841–845.
47.
Shaamash, A.H., E.D. Elsonosy, M.M. Zakhari, S.H. Radwan, H.M. El-Dien (2001) Placental nitric oxide synthase (NOS) activity and nitric oxide (NO) production in normal pregnancy, pre-eclampsia and eclampsia. Int J Gynaecol Obstet 72: 127–133.
48.
Sorrell, J.M., A.I. Caplan (2009) Fibroblasts-a diverse population at the center of it all. Int Rev Cell Mol Biol 276: 161–214.
49.
Suciu, L., L.M. Popescu, M. Gherghiceanu (2007) Human placenta: de visu demonstration of interstitial Cajal-like cells. J Cell Mol Med 11: 590–597.
50.
Takizawa, T., H. Yoshikawa, M. Yamada, H. Morita (2002) Expression of nitric oxide synthase isoforms and detection of nitric oxide in rat placenta. Am J Physiol Cell Physiol 282: C762–C767.
51.
Weibel, E. (1979) Stereological Methods: Practical Methods for Biological Morphometry. New York, Academic Press.
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