FIBROBLASTS IN NORMAL AND PATHOLOGICAL TERMINAL DIFFERENTIATION, AGING, APOPTOSIS AND TRANSFORMATION

Fibroblast populations have been considered as homogeneous non-differentiating cell populations until nowadays. Such undefined fibroblast populations have been predominant cell systems for qualitative and/or quantitative studies in general cell biology, biochemistry and virology, and more specialized issues like differentiation, aging, apoptosis and transformation. Most data obtained from such investigations are inconsistent to such an extent, that many scientists consider the fibroblast cell system to be unsuited for studies of the molecular mechanisms of developing cell populations. When analyzed with concepts and methods routinely applied for the study of the molecular biology of cells in stem cell systems, it has been demonstrated, that fibroblast cell systems of Valo-chicken, C3H-mice, BN-rats, and man are stem cell systems. In the fibroblast stem cell system 11 cell-types with biological and biochemical individuality develop along a 11-stage differentiation sequence in five compartments under the control of genetic programs. This differentiation sequence is maintained in fibroblast populations in pathological manifestations, like Duchenne muscular dystrophy, fibrosis, as well as in transformed, neoplastically transformed, and revertant cell lineages. Evidence is accumulating, which makes it very likely, that all cell systems are stem cell systems with a design resembling the nature of the fibroblast stem cell system. Nowadays research in the field of molecular cell biology is undertaken with very advanced molecular methods, but unfortunately in most instances with poorly defined or undefined biological material or cell systems.