We have recently reported an alternative cell therapy approach to induce angiogenesis. The approach is based on small organ fragments--micro-organs (MOs)--whose geometry allows preservation of the natural epithelial/mesenchymal interactions and ensures appropriate diffusion of nutrients and gases to all cells. We have shown that lung-derived MOs, when implanted into hosts, transcribe a wide spectrum array of angiogenic factors and can induce an angiogenic response that can rescue experimentally induced ischemic regions in mice. From a clinical perspective, skin-derived MOs are particularly appealing as they could readily be obtained from a skin biopsy taken from the same target patient. In the present work we have investigated the angiogenesis-inducing capacity of rabbit and human skin-derived micro-organs in vitro and in vivo. Rabbit skin MOs were implanted into homologous adult rabbits and human skin MOs were encapsulated and implanted into xenogenic mice. Skin-derived MOs, as lung-derived MOs, were found to secrete a whole array of angiogenic factors and to induce a powerful angiogenic response when implanted back into animals. We believe the approach presented suggests a novel, efficacious and simple approach for therapeutic angiogenesis.