TELOCYTES – a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal‐Like Cells (ICLC) to TELOCYTES

Abstract

Ramon y Cajal discovered a particular cell type in the gut, which he named ‘interstitial neurons’ more that 100 years ago. In the early 1970s, electron microscopy/electron microscope (EM) studies showed that indeed a special interstitial cell type corresponding to the cells discovered by Cajal is localized in the gut muscle coat, but it became obvious that they were not neurons. Consequently, they were renamed ‘interstitial cells of Cajal’ (ICC) and considered to be pace-makers for gut motility. For the past 10 years many groups were interested in whether or not ICC are present outside the gastrointestinal tract, and indeed, peculiar interstitial cells were found in: upper and lower urinary tracts, blood vessels, pancreas, male and female reproductive tracts, mammary gland, placenta, and, recently, in the heart as well as in the gut. Such cells, now mostly known as interstitial Cajal-like cells (ICLC), were given different and confusing names. Moreover, ICLC are only apparently similar to canonical ICC. In fact, EM and cell cultures revealed very particular features of ICLC, which unequivocally distinguishes them from ICC and all other interstitial cells: the presence of 2–5 cell body prolongations that are very thin (less than 0.2 μm, under resolving power of light microscopy), extremely long (tens to hundreds of μm), with a moniliform aspect (many dilations along), as well as caveolae. Given the unique dimensions of these prolongations (very long and very thin) and to avoid further confusion with other interstitial cell types (e.g. fibroblast, fibrocyte, fibroblast-like cells, mesenchymal cells), we are proposing the term TELOCYTES for them, and TELOPODES for their prolongations, by using the Greek affix ‘telos’.

Telocytes play a key role in prostate tissue organisation during the gland morphogenesis

“…These cells were described in the prostate prior to the description of prostatic telocytes and to them were assigned the generic name of interstitial cajal‐like cells (ICLCs) 45. The characterization of telocytes was useful to avoid multiple ambiguous terminologies for CD34‐positive fibroblast‐like cells found in various organs, our data confirm the existence of fibroblast‐like CD34 and CD34/c‐Kit‐positive cells, consisting of prostatic telocytes, however, the data also point to the existence of fibroblast‐like cells c‐Kit positive and CD34 negative 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, to which the canonical definition of telocytes is not applied. Moreover, in structural terms we obtain some evidence of the existence fibroblast‐like cells that possess shorter and thicker cytoplasmic process at the periphery of the developing perialveolar smooth muscle, in which c‐Kit‐positive/CD34‐negative cells are verified.…”

“…In addition, our data point to the existence of fibroblast‐like cells in the prostate that are c‐Kit positive and CD34 negative, which escape the typical immunolabelling profile of telocytes (CD34 or CD34/c‐Kit positive) 9, 10, 11, 12, 13, 14, 15, 16, 17 And in the face of the immunolabelling profile of these factors during prostate development, in addition to some ultrastructural evidence, it is suggested that some telocytes (CD34 or CD34/c‐Kit positive) present at the periphery of the developing smooth muscle of alveoli could differentiate into c‐Kit‐positive and CD34‐negative fibroblast‐like cells that resemble ICCs. However, further studies will be needed to test this hypothesis.…”

“…Telepodes can be divided into dilated portions, podoms and fibrillar‐like sections called podomers 8, 9. Several functions of telocytes have been proposed, which vary from organ to organ, such as organisation of the stroma through modulation of intercellular communication 15, regeneration of cardiac muscle 10, immune response in the duodenum 11, contractility of the uterus 12 and in intercellular electrical communication 18, among others.…”

Telocytes in ileum of the Chinese giant salamander: ultrastructural evidence

“…Many investigations have documented that TCs and their Tps are resident in various organs of many mammals, including human, pig, gerbil, mouse, rat and degus 1, 2, 3, 4, 5. Studies on TCs and Tps have also been reported in lower animals, such as newts, zebrafish and turtles 6, 7.…”

A comprehensive guide to telocytes and their great potential in cardiovascular system

“…The main feature that distinguishes TCs from any other cells are their very long and thin prolongations, which are named telopodes (Tps) (1). The history of their development derives in a straight line from Interstitial Cajal Cells (ICC).…”