Advanced imaging of transplant survival, fate, differentiation, and integration.

Stem cell-based therapy trials for the treatment of neurodegenerative diseases such as Parkinson's and Huntington's disease are being actively prepared both at the preclinical and clinical level. Preclinical validation of these stem cell transplantations necessitates to implement a translational continuum to take one pluripotent stem cell through the point of "first-in-man" clinical trial. Main steps along this translational continuum include stem cell GMP production, in vitro optimization of differentiation protocols necessary to direct stem cells to the desired neuronal phenotype, and evaluation of functional efficacy in animal models including large animal models. Whereas the first two steps only require in vitro techniques and can be expedited smoothly, the last step is generally time consuming as functional assessment requires transplantation of the animal models with sufficient time for cells to develop, reconnect, and exert their therapeutic effect (around 40 weeks for human cells in the rodent brain). In such a context, brain imaging techniques that allow noninvasive longitudinal evaluation/characterization of the grafted cells in the living animals have the potential to speed-up the evaluation of candidate cell lines. This chapter describes an assemblage of imaging methods that over the years proved useful in preclinical and clinical applications for cell therapy, providing in a noninvasive way unique insights on graft cellular composition, phenotypic differentiation, as well as signs of hyperproliferation and/or immunological rejection and inflammation.