Interstitial Cajal‐like cells (ICLC) in atrial myocardium: ultrastructural and immunohistochemical characterization

Abstract

We have previously reported (Hinescu & Popescu, 2005) the existence of interstitial Cajal-like cells (ICLC), by transmission electron microscopy, in human atrial myocardium. In the present study, ICLC were identified with non-conventional light microscopy (NCLM) on semi-thin sections stained with toluidine blue and immunohistochemistry (IHC) for CD117/c-kit, CD34, vimentin and other additional antigens for differential diagnosis. Quantitatively, on semi-thin sections, ICLC represent about 1–1.5% of the atrial myocardial volume ( vs. ±45% working myocytes, ˜2% endothelial cells, 3–4% for other interstitial cells, and the remaining percentage: extracellular matrix). Roughly, there is one ICLC for 8–10 working atrial myocytes in the intercellular space, beneath the epicardium, with a characteristic (pyriform, spindle or triangular) shape. These ICLC usually have 2–3 definitory processes, emerging from cell body, which usually embrace atrial myocytes (260 nm average distance plasmalemma/sarcolemma) or establish close contact with nerve fibers or capillaries (˜420 nm average distance to endothelial cells). Cell prolongations are characteristic: very thin (mean thickness = 0.150±0.1 μm), very long for a non-nervous cell (several tens of μm) and moniliform (uneven caliber). Stromal synapses between ICLC and other interstitial cells (macrophages) were found ( e.g. in a multicontact type synapse, the average synaptic cleft was ˜65 nm). Naturally, the usual cell organelles (mitochondria, smooth and rough endoplasmic reticulum, intermediate filaments) are relatively well developed. Caveolae were also visible on cell prolongations. No thick filaments were detected. IHC showed that ICLC were slightly and inconsistently positive for CD117/c-kit , variously co-expressed CD34 and EGF receptor , but appeared strongly positive for vimentin , along their prolongations. Some ICLC seemed positive for α-smooth muscle actin and tau protein , but were negative for nestin, desmin, CD13 and S-100 . In conclusion, we provide further evidence of the existence of ICLC in human atrial myocardium, supporting the possible ICLC role in pacemaking, secretion (juxta- and/or paracrine), intercellular signaling (neurons and myocytes). For pathology, ICLC might as well be ‘players’ in arrhythmogenesis and atrial remodeling.

Processus and recessus adhaerentes: giant adherens cell junction systems connect and attract human mesenchymal stem cells

“…Remarkably, such long processes have also been seen on cells containing additional differentiation-specific proteins such as smooth or cardiac muscle α-actins or diverse cytokeratins. In this context, a specific type of interstitial cell with two or three long (up to 30 μm) thin cell processes has recently been identified in human atrial myocardium (Hinescu et al 2006).…”

Innovations in Clinical Cardiac Electrophysiology: Challenges and Upcoming Solutions in 2018 and Beyond

“…Interstitial Cajal-like cells (also known as telocytes) have been demonstrated in numerous extra-gastrointestinal sites, including in human atria and the ventricles. 122,123 These cells may interact with stem cells and modulate cardiac regeneration. Although these cells are rare in number in comparison with myocytes, they have multiple elongated processes capable of interfacing with multiple myocytes through gap junctions.…”

Evidence of interstitial Cajal-like cells in human gallbladder

“…Disturbances in gastrointestinal motility after the loss of, or damage to, ICCs have been widely reported in several clinical and pathological conditions, including gastroparesis, constipation, achalasia, Chagas disease, Hirschprung's disease, congenital hypertrophic pyloric stenosis, intestinal pseudo-obstructions, and diverticular disease of the colon [6,[8][9][10]. Many authors have investigated cells similar to ICCs located in other organs, including the pancreas, urether, urethra, bladder, blood vessels, male and female reproductive organs, mammary glands, placenta, heart, and lungs [8,[11][12][13][14][15][16][17]. Cells that resemble archetypal enteric ICCs are referred to as interstitial Cajal-like cells (ICLCs).…”