Synthetic organogenesis: using in vivo cellular reprogramming to induce ectopic organs

Our long-term goal is to find ways to induce synthetic organogenesis, that is to produce miniorgans that function in vivo. With the term "miniorgan" we mean multicellular assemblies that i) contain all major cell types normally present in an organ, ii) that show morphological organization within the miniorgan, and iii) that functionally integrate into the host tissue. Thus, miniorgans may be smaller than regular organs, but they are fully functional. The ability to produce functional miniorgans would signify a quantum leap for regenerative medicine, drug development, and stem cell research. Currently used attempts to restore the function of damaged organs involve the transplantation of stem or progenitor cells (Stem cell therapy) or to trigger the generation of missing/defective cell types by cellular reprograming. However, these approaches face serious limitations: In vivo reprogramming is very inefficient and reprogrammed or transplanted cells poorly self-organize and integrate into the host. In the proposed research we will use novel in vivo approaches to tackle these fundamental problems. Our research will thus show how to harness the ability of biological systems to selforganize for the advancement of regenerative medicine.