Novel type of interstitial cell (Cajal-like) in human fallopian tube
Article first published online: 1 MAY 2007
Journal of Cellular and Molecular Medicine
Volume 9, Issue 2, pages 479–523, April 2005
How to Cite
Popescu, L.M., Ciontea, S. M., Cretoiu, D., Hinescu, M.E., Radu, E., Ionescu, N., Ceausu, M., Gherghiceanu, M., Braga, R. I., Vasilescu, F., Zagrean, L. and Ardeleanu, C. (2005), Novel type of interstitial cell (Cajal-like) in human fallopian tube. Journal of Cellular and Molecular Medicine, 9: 479–523. doi: 10.1111/j.1582-4934.2005.tb00376.x
- Issue published online: 1 MAY 2007
- Article first published online: 1 MAY 2007
- Received: March 21, 2005, Accepted: May 6, 2005
- interstitial cells of Cajal;
- uncommitted progenitor cells;
- intercellular signaling;
- calcium release units;
- uterine tube;
- tubal endocrine cells
We describe here - presumably for the first time-a Cajal-like type of tubal interstitial cells (t-ICC), resembling the archetypal enteric ICC. t-ICC were demonstrated in situ and in vitro on fresh preparations (tissue cryosections and primary cell cultures) using methylene-blue, crystal-violet, Janus-Green B or Mito Tracker-Green FM Probe vital stainings. Also, t-ICC were identified in fixed specimens by light microscopy (methylene-blue, Giemsa, trichrome stainings, Gomori silver-impregnation) or transmission electron microscopy (TEM). The positive diagnosis of t-ICC was strengthened by immunohistochemistry (IHC; CD117/c-kit+ and other 14 antigens) and immunofluorescence (IF; CD117/c-kit+ and other 7 antigens). The spatial density of t-ICC (ampullar-segment cryosections) was 100–150 cells/mm2. Non-conventional light microscopy (NCLM) of Epon semithin-sections revealed a network-like distribution of t-ICC in lammina propria and smooth muscle meshwork. t-ICC appeared located beneath of epithelium, in a 10–15μ thick ‘belt’, where 18±2% of cells were t-ICC. In the whole lamina propria, t-ICC were about 9%, and in muscularis ∼7%. In toto, t-ICC represent ∼8% of subepithelial cells, as counted by NCLM. In vitro, t-ICC were 9.9±0.9% of total cell population.
TEM showed that the diagnostic ‘gold standard’ (Huizinga et al., 1997) is fulfilled by ‘our’ t-ICC. However, we suggest a ‘platinum standard’, adding a new defining criterion - characteristic cytoplasmic processes (number: 1–5; length: tens of μm; thickness: ±0.5μ; aspect: moniliform; braching: dichotomous; organization: network, labyrinthic-system). Quantitatively, the ultrastructural architecture of t-ICC is: nucleus, 23.6±3.2% of cell volume, with heterochromatin 49.1±3.8%; mitochondria, 4.8±1.7%; rough and smooth endoplasmic-reticulum (1.1±0.6%, 1.0±0.2%, respectively); caveolae, 3.4±0.5%. We found more caveolae on the surface of cell processes versus cell body, as confirmed by IF for caveolins. Occasionally, the so-called ‘Ca2+-release units’ (subplasmalemmal close associations of caveolae+endoplasmic reticulum±mitochondria) were detected in the dilations of cell processes. Electrophysiological single unit recordings of t-ICC in primary cultures indicated sustained spontaneous electrical activity (amplitude of field potentials: 57.26±6.56mV).
Besides the CD117/c-kit marker, t-ICC expressed variously CD34, caveolins 1&2, α-SMA, S-100, vimentin, nestin, desmin, NK-1. t-ICC were negative for: CD68, CD1a, CD62P, NSE, GFAP, chromogranin-A, PGP9.5, but IHC showed the possible existence of (neuro)endocrine cells in tubal interstitium. We call them ‘JF cells’.
In conclusion, the identification of t-ICC might open the door for understanding some tubal functions, e.g. pace-making/peristaltism, secretion (auto-, juxta- and/or paracrine), regulation of neurotransmission (nitrergic/purinergic) and intercellular signaling, via the very long processes. Furthermore, t-ICC might even be uncommitted bipotential progenitor cells.