Investigations into mechanisms modulating proliferation, differentiation, and apoptosis in cultured liver, adrenal, skin, and bone cells

The intricate modulatory roles played by manifold hormones, growth factors, cytokines, extracellular calcium concentrations, intracellular second messengers, protein kinases, and nuclear poly(ADP-ribose) polymerase in proliferative, differentiative, and apoptotic processes have been the subject of investigations that were carried out by means of in vitro either primary or secondary/tertiary cultures of differentiated epithelial (hepatocytes, keratinocytes, and adrenocytes) and connective tissue cells (osteoblasts and fibroblasts) obtained from man and/or other mammalians. In most cases, an ad hoc model system, in which cells were floated on the top of the growth medium and, hence, could enjoy nearly normal respiratory exchanges, was used. Such a system increased cell viability and the ability of parenchymal epithelial cells to respond to extremely low concentrations of growth factors, hormones, and pharmaco-toxicological agents in a way conceivably very close to their behaviour in vivo.