The first limitation is based on characteristic differences between particular pluripotent cell lines (Osafune et al., 2008; Hu et al., 2009; Bock et al., 2011). These differences influence the properties of the neurons that are derived from these lines. For example, neurons derived by the same protocol from two different ES cell lines exhibited quite distinct properties (Wu et al., 2007). Moreover, ES and iPS cell lines may change as a function of time in culture (Mekhoubad et al., 2012). A systematic comparison of the neural differentiation potential of different ES and iPS cell lines revealed a large variation in conversion efficiency, and it is likely that maturation stages and functional properties of the resulting neurons are also variable (Hu et al., 2009).