Fig. 1. Current and future approaches to tissue and organ regeneration. At present, the replacement of an organ, such as a whole limb, is carried out through surgical transplantation or implantation of prosthetic devices (bottom panel). Therapeutic stem cell strategies (top panel) present an alternative approach to identifying the controls that drive these cells to form the various specialized cell types that comprise an organ. Tissue engineering (middle panel) focuses mostly on the cell-to-tissue transition by combining cells with scaffolds that mimic the ECM to promote multicellular assembly and provide mechanical functions. Future approaches are likely to integrate stem cells into tissue-engineered products, or use implantable engineered materials to guide stem cell behavior in vivo. Another developmental biology-based approach, which could promote the entire cell-to-organ regeneration cascade, requires identification of `master regulators' that are analogous to those that produce whole-limb and appendage regeneration in lower organisms.