Here, we review the history, morphology, immunohistochemical phenotype, and presumptive roles of a new type of interstitial tissue cells, formerly called interstitial Cajal-like cells (ICLC) and by 2010 named 'telocytes' (TC). Many different techniques have been used to characterize TC and provide their unequivocal identification: (i) in vitro, cultures and isolated cells; (ii) in situ, fixed specimens examined by light and fluorescence microscopy, transmission (TEM) and scanning electron microscopy, and electron tomography. TEM allowed sure identification and characterization of the most peculiar feature of TC: the long, thin, and convoluted prolongations named 'telopodes'. An enormous variety of antibodies have been tested, but presently none are reliable to specifically label TC. TC have a mesenchymal origin and are resident connective tissue (stromal) cells. Possible identification with 'already identified' stromal cell types (fibroblasts, fibrocytes, fibroblast-like cells, and mesenchymal stromal cells) is discussed. We conclude that in adulthood, most of the TC have the morphology of fibrocytes. Apparently, immunocytochemistry suggests that a variety of TC populations showing different, likely organ-specific, immunophenotypes might exist. Several roles have been hypothesized for TC: mechanical roles, intercellular signaling, guiding and nursing of immature cells during organogenesis, and being themselves a pool of precursors for many of the mesenchyme-derived cells in adulthood; however, none of these roles have been proven yet. On the basis of the available data, we propose TC may be key players in organ regeneration and repair.

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