3.3 Preclinical Studies
The purpose of preclinical studies is to (a) provide evidence of product safety and (b) establish proof-of-principle for therapeutic effects. International research ethics policies, such as the Declaration of Helsinki (1964) and the Nuremberg Code (1949), strongly encourage the performance of non-human animal studies prior to clinical trials. Before initiating clinical studies with stem cell-based interventions in humans, researchers should have persuasive evidence of safety and the potential for clinical utility in appropriate in vitro and/or animal models. These preclinical studies must be rigorously designed and have been subject to regulatory oversight and reviewed independently prior to the initiation of clinical trials. This helps ensure that trials are scientifically, medically, and ethically warranted.
Cell-based interventions offer unique challenges for preclinical studies. In some cases, homologous cells in the same species are unavailable. Immune-suppressed animal models, while useful, do not permit an understanding of the effect of the immune system on transplanted cells, or, more often, they may not share all the same biological properties of their human counterparts. Since transplanted cells are considerably more complex and can change after transplantation in unpredictable ways, extrapolating cell therapies in an animal model to humans is even more challenging than for small molecule therapeutic candidates.