The last mitoses of the human fibroblast proliferative life span, physiopathologic implications

Normal human fibroblasts, after exhausting their proliferative life span, enter a post-mitotic stage where they remain metabolically active. It has been suggested that this is a terminal differentiation process. During the last mitoses of the cell population proliferative life span, sudden events take place in the genome consisting of deviations from the semiconservative distribution of DNA between sister cells, decondensation of heterochromatin, reorganizations in the high order DNA structure and the presence of extrachromosomal circular DNA. These events could correspond to the 'quantal mitosis', the last mitosis where cells become irreversibly committed to differentiation. The identification of the ultrastructural characteristics of the terminal cell allowed for the first time to ascertain the presence of these cells in a tissue in vivo. The terminal cell obtained through serial proliferation in vitro, was found only in pathological states. A cell with some, though not all of the characteristics of the terminal in vitro fibroblast, was present in vivo in normal skin in an amount unrelated to the age of the donor.