Preclinical studies on stem cells as a prelude to clinical application: animal models or alternatives?

Stem cells offer an unequalled opportunity for the therapy of a wide array of human acute and chronic diseases for which no efficient surgical or pharmacological treatments exist. Stem cells are considered a valid alternative in human disease modeling and drug testing. However, when cell therapy is considered, stem cells have to be functionally studied, not only in vitro, in silico and ex vivo, but also on the organism as a whole as a prelude to its clinical application. There are a large number of diseases for which stem cell therapies have been studied in animal models, and have provided outputs applicable to human clinical trials. Mostly rodents are used for proof-of-principle studies, but larger animals may provide the ultimate validation, by accurately addressing potential risks and benefits of cell-based therapy before translation to the clinic. In this review, we discuss the pros and cons of the use of animal models for stem cell research and the much-sought after alternatives for this mission of the 21st century.