Terminal differentiation - A challenge in regeneration Special Issue on the IEB-Symposium at the 'Inner Ear Biology Workshop' 2005, held on Saturday, 17th September 2005, in Tubingen, Germany.

摘要

Regeneration of hair cells continues to hold promise as the major hope to restore hearing and balance compromised by disorders of the inner ear. Despite the impressive progress of research seen over the last two decades, induction of functional regeneration of hair cells in the mammalian sensory epithelia and, in particular, in the organ of Corti remains the ultimate goal of biomedical research in this area. One of the major biological barriers for the regenerative process is terminal differentiation. The term 'terminal differentiation' covers general cell biological features such as specific gene expression, irreversible cessation of cell division and differentiation of a fully matured functional cell phenotype. Terminal differentiation can be observed in a large number of highly-differentiated tissues such as the sense organs, the central nervous system or the heart muscle, all of which are unable to regenerate spontaneously. From the viewpoint of regeneration, the cell biological state of terminal differentiation has two challenging perspectives. The first challenge is to induce terminally differentiated cells towards a regenerative response, and the second challenge is to navigate a regenerative response towards the functional terminally differentiated phenotype. Many questions have to be addressed in the seemingly contradictory context of terminal differentiation and regeneration. These include the discussion of key regulators of cell fate and cell proliferation in the inner ear, mechanisms specifying cellular subtypes, such as supporting cells and hair cells, the intrinsic and extrinsic characteristics of cells with stem-cell properties and the determinants for losing and gaining the potential for phe-notypic differentiation. Finally, how can reactivation of the determinants of cellular genesis be used in the adult inner ear with the aim of cellular reconstitution and, ultimately, to functionally restore the diseased inner ear in patients?