This proposal aims to develop and implement efficacy of clinical trials with adult, tissue stem cells for degenerative diseases of epithelia and skeletal muscle. Extraordinary progress in the understanding of several key features of stem cells has been rapidly translated into novel cell therapy protocols that have yielded positive results in pre-clinical models of genetic and acquired diseases and in the first clinical trials. Much remains to be done on the basic biology of stem cells to provide new tools for cell therapy trials. Also transplantation related issues, such as engraftment, angiogenesis, tissue remodeling and immune response remain to be addressed. In general, cell therapy necessitates a continuous cross-talk among biologists and clinicians as well as crossing boundaries among different tissues/diseases. Despite many structural and functional differences, epithelia and skeletal muscle share some key features such as spatially ordered cell architecture, centered on a supporting basal lamina to which stem cells are anchored. Indeed mutations in structural proteins linking the cell membrane to the basal lamina are responsible for similarly devastating diseases such as muscular dystrophies and epidermolysis bullosa. A multi-tissue approach allows jointly addressing and solving not only scientific and clinical problems but also regulatory and ethical issues related to these novel procedures. Finally, sharing high valued dedicated platforms such as large animal facilities and GMP cell culture facilities increases performance and reduces costs. Based on these considerations, a network of internationally recognized experts in muscle and epithelial cell biology, immunology, angiogenesis, and molecular pharmacology with two stem cell-based Companies has been assembled, creating a synergistic approach that will increase the chance of success for ongoing and future clinical trials with stem cells, that are integral part of this proposal.