Modeling to Optimize Terminal Stem Cell Differentiation

Figure 2

ES cell-derived DA neurogenesis and its implication for transplantation. In vitro and in vivo differentiated ES cells differentiate into immature neural precursors, which develop into mature adult DA neurons. During cell development, three major phases take place: commitment into the neuroectodermal cell lineage, maturation into the DA-specific neuronal phenotype, and maintenance of cell function. In these phases, the developed cells are either mitotic, for example, ES and lineage-committed immature precursors or terminally differentiated immature or mature DA neurons. For transplantation purposes, it is critical to determine the optimal state of the transplanted cells. For example, it has been shown that transplantation of ES cells in the brain showed good survival and differentiation into functional DA neurons with integration in the brain circuitry but partially developed into teratomas. Some of these observations have also been made by transplantation of immature precursors (unpublished observations). In contrast, transplantation of fully differentiated mature DA neurons did not reveal teratoma formation, but, poor survival and suboptimal function in the brain. These results demonstrate that certain criteria for a DA graft need to be fulfilled in order to achieve optimal results in future ES cell-based transplantation paradigms for PD, which can be summarized as follows: good survival, proper function, and integration into the brain circuitry with no immunogenicity and tumor formation (from [10]).