Advances in stem cell research and tissue engineering in recent decades have led, i.a., to the generation of induced pluripotent stem cells and biocompatible artificial scaffolds, inspiring hope for future regenerative therapies. Progress in the field of regenerative medicine is, however, inevitably difficult applying the mammalian model organisms traditionally used in biomedical research, owing to the lack of tissue regenerative potential in these organisms. In contrast, urodele amphibians possess impressive regenerative capabilities at both tissue, organ, and structural level, and are apt models for regenerative biology and medicine, exemplified in the iconic Mexican axolotl (Ambystoma mexicanum). In this talk I will present the axolotl as an important comparative model for unraveling the mechanisms of intrinsic tissue regeneration in general and in particular as a model for tissue regeneration following myocardial infarction as well as a model for stem cell tracking using MRI for non-invasive evaluation of future regenerative therapies. The axolotl heart has been described to recover completely following partial ventricular amputation of the apex, serving as a model for regeneration in a relatively simple structure in the sense of only a few different tissues involved. Removal of heart tissue in the form of partial amputation is, however, not a very clinically relevant situation, on the other hand regeneration following myocardial infarction is highly clinically relevant. We have developed an axolotl myocardial infarction model that allows for description and discovery of regenerative events in the process of heart repair. In this talk I will present our latest discoveries of basic molecular and cellular mechanism that are activated at the initiation of heart regeneration in the axolotl. One fundamental challenge of future stem cell therapies will be the ability to monitor the progress of therapy in the sense of being able to track injected stem cell. The technique to accomplish this has to be non-invasive – there is no point in regenerating tissue, if this is destroyed by biopsies later on to ensure that regeneration has in fact taken place. Additionally, cell tracking technology will have to be safe and repetitive to allow for follow up evaluations. Ultrasmall superparamagnetic iron oxide particles (USPIO), nanoparticles containing an iron oxide core and a biocompatible coating, have been suggested and applied for non-invasive and safe stem cell tracking in preclinical studies, as cells labeled with these particles can be detected with MRI due to their ferrous core. We have developed a fluorophore conjugated USPIO detectable with MRI and optical imaging and tested the tracking methodology in the axolotl, in this situation serving as a model of intrinsic regeneration.