A distinct type of cell in myocardium: interstitial Cajal‐like cells (ICLCs)

Abstract

The existence of a novel type of interstitial cells in the heart, interstitial Cajal-like cells (ICLCs), had been described for the first time in 2005. Their identification was mainly based on ultrastructural criteria: very long (tens up to hundreds of micrometres) and moniliform prolongations, which are extremely thin (less than 0.2 μm), below the resolving power of light microscopy. Myocardial ICLCs were also identified by methylene-blue vital staining, silver impregnation, and immunoreactivity for CD 34, vimentin, CD117/c-kit, etc. Although a series of studies provided evidence for the existence of ICLCs in human atria and rat ventricles, further investigations in other laboratories, using additional techniques, are required to substantiate the consistency of these findings. Here we provide further evidence for the existence of ICLCs in human and mammalian hearts (by transmission and scanning electron microscopy, as well as confocal laser scanning microscopy). Noteworthy, we confirm that ICLCs communicate with neighbouring cells via shedding (micro)vesicles. Although these so-called ICLCs represent a distinct type of cells, different from classical interstitial cells of Cajal, or fibroblasts, their role(s) in myocardium remain(s) to be established. Several hypotheses are proposed: (i) adult stromal (mesenchymal) stem cells, which might participate in cardiac repair/remodelling; (ii) intercellular signalling (e.g. via shedding microvesicles); (iii) chemo-mechanical transducers and (iv) players in pacemaking and/or arrhytmogenesis, and so on.

Telocytes as supporting cells for myocardial tissue organization in developing and adult heart

“…3B). These latter cells displayed the typical ultrastructural phenotype described previously for cardiac telocytes [5,7,9]. In the newborn heart, such telocytes were found closely Fig.…”

“…Of note, stromal cells bearing long cellular extensions have been also described in most mature organs, although they have been long neglected and simplistically labelled as fibroblasts. However, this view is being rapidly changing due to the recent observations by Popescu and coworkers who found stellate-shaped stromal cells occurring in several adult tissues and organs, where they may represent a distinct cell type from the classical fibroblasts [5]. [6].…”

“…[6]. Indeed, their peculiar ultrastructural phenotype is currently considered as the only reliable hallmark for these cells, which do not possess a unique antigenic profile [5][6][7].…”

Expression and distribution of key enzymes of the cyclic GMP signaling in the human clitoris: relation to phosphodiesterase type 5 (PDE5)

“…In some of the cells, PDE2 was found co-localized with vimentin, a specific feature of ICs and neurons, thereby confirming earlier findings describing immunolabeling for ICs in cardiac tissue and the urogenital tract (Figure 3c). [13][14][15][16][17] Staining specific for PDE11A (dual-substrate PDE) was observed in single nerve trunks located in the clitoral stroma (Figure 1f). In contrast, no labeling indicating PDE2 or PDE5 was observed in nerve fibers or nerve endings (Table 1).…”

“…23 26,27 ICs have also been identified by immunoreactivity for the transmembrane receptor protein c-kit, the gap junction protein connexin 43 or vimentin, an intermediate filament subunit of mesenchymal cells. 13,14,16 Usually, ICs can be found adjacent to their target cells, such as smooth muscle cells, epithelial cells or nerve endings. 28 It has been suggested that ICs may have a pivotal role as so-called pacemakers and mediators of neurotransmission in the bladder, urethra and penile erectile tissue.…”