Metaplasia and transdifferentiation: from pure biology to the clinic

Key Points 'Metaplasia' is defined as the conversion of one tissue type to another, whereas 'transdifferentiation' is defined as the conversion of one differentiated cell type to another. Despite scepticism arising from exaggerated claims about the reprogramming of bone-marrow stem cells, these phenomena do occur on occasion. Long standing examples are the phenomena of transdetermination in Drosophila melanogaster and the types of epithelial metaplasia in which patches of one epithelium are found in the midst of another. The cause of such events is the alteration of expression of the transcription factors that encode the specification of the tissue types during embryonic development. The alteration can arise from somatic mutation, epigenetic change or change of regulation by an extracellular signal. Metaplasias are associated with tissue damage because the process of regeneration gives small foci of ectopic tissue the opportunity to grow into large patches. Many metaplasias are understood in molecular detail, and the following are described: transdetermination of leg to wing in D. melanogaster ; intestinal metaplasia in human and mouse; vaginal adenosis in women; switching of B lymphocytes to macrophages; transformation of exocrine pancreas to hepatocytes; and Wolffian regeneration of the lens from the iris in newts. The nature of the differentiated state, and that of the commitment of undifferentiated stem and progenitor cell populations remains poorly understood, although it is likely that chromatin structure is involved. Therapeutic applications can be imagined in which the expression of relevant transcription factors is modified. These could potentially be used to inhibit the formation of harmful metaplasias, such as those that predispose individuals to cancer. They could also be used to generate desirable cell types, such as pancreatic β cells, for transplantation therapy. Transformations from one tissue type to another are an established set of phenomena that can be explained by the principles of developmental biology. So, can we deliberately reprogramme cells from one tissue type to another to generate new therapies for human diseases? Transformations from one tissue type to another make up a well established set of phenomena that can be explained by the principles of developmental biology. Although these phenomena might be rare in nature, we can now imagine the possibility of deliberately reprogramming cells from one tissue type to another by manip