Attention is drawn to the importance of selecting appropriate matched controls because caseCcontrol cell differences could arise from sampling bias and disease-associated differences may result from particular comparator control cells (Zhu et al., 2011; Maury et al., 2012). been genetic diseases, iPSCs have been generated from patients with complex diseases (schizophrenia and sporadic Parkinsons disease). Some genetic diseases are also modeled in embryonic stem cells (ESCs) generated from blastocysts rejected during fertilization. Neural stem cells have been isolated from post-mortem brain of Alzheimers patients and neural stem cells generated from biopsies of the olfactory organ of patients is another approach. These olfactory neurosphere-derived cells demonstrate robust disease-specific phenotypes in patients with schizophrenia and Parkinsons disease. HCS is already in use to find small molecules for the generation and differentiation of ESCs and iPSCs. The challenges for using stem cells for drug discovery are to develop robust stem cell culture methods that meet the rigorous requirements for repeatable, consistent quantities of defined cell types at the industrial scale necessary for HCS. fertilization and pre-implantation genetic diagnosis (Stefanova et al., 2012). Although these are not strictly patient-derived they carry specific genetic mutations or deletions that would normally lead to disease. Induced pluripotent stem cells (iPSCs) from patients have become the dominant choice for patient-derived pluripotent stem cells. A recent review lists 18 diseases for which ESCs have been derived, compared with 40 for which iPSCs have been derived (Grskovic et al., 2011). At this time many of the publications in this field are mainly demonstrations that pluripotent stem cells have been derived, often without demonstrating a disease-phenotype. Some show that the pluripotent cells can be differentiated into specific cell types of interest and some demonstrate deficits in cellular functions compared to control cells, as proof-of-principle for disease modeling (Grskovic et al., 2011; Maury et al., 2012). No doubt the numbers of diseases for which iPSCs are available will increase greatly in the next few years and deeper analyses of their functions will become forthcoming. It is a major challenge for the field to move beyond the proof-of-principle stage to finding of fresh aspects of disease biology and fresh targets for restorative intervention. The list of neurological diseases and conditions for which ESCs or iPSCs have been derived is largely Gdnf limited to monogenic diseases including CharcotCMarieCTooth disease type 1A, Down syndrome-trisomy 21, familial amyotrophic lateral sclerosis, familial dysautonomia, familial Parkinsons disease, Fragile X syndrome, Friedreich ataxia, Gauchers disease, Huntingtons disease, Rett syndrome, Spinal muscular atrophy, spinocerebellar ataxia types 2 and 7, and X-linked adrenoleukodystrophy (Grskovic et al., 2011; Maury et al., 2012; Rajamohan et al., 2013). It Baohuoside I is thought that diseases of complex genetics and environmental risk factors may be harder to model with pluripotent stem cells but patient-derived iPSCs have been generated from individuals with Parkinsons disease (Soldner et al., 2009) and schizophrenia (Brennand et al., 2011; Pedrosa et al., 2011). Patient-derived iPSCs from people with sporadic Parkinsons disease were differentiated into dopaminergic neurons but failed to show an obvious difference in phenotype compared to control cells (Soldner et al., 2009). Similarly, a disease-associated phenotype could not be shown in iPSCs from two instances of sporadic Alzheimers disease (Israel et al., 2012). In one study, iPSCs from schizophrenia individuals were differentiated into neurons and gene manifestation profiling recognized a cluster of Baohuoside I differentially indicated genes involved in neurogenesis, neuronal differentiation, axon guidance, and adhesion with another cluster of differentially indicated genes involved in cell cycle rules (Pedrosa et al., 2011). A second study in schizophrenia showed that neurons differentiated from patient-derived iPSCs Baohuoside I experienced reduced neurite quantity and reduced connectivity with additional neurons and reduced glutamate receptor manifestation (Brennand et al., 2011). These studies of patient-derived iPSCs from schizophrenia individuals demonstrate that such models can expose disease-associated cellular deficits in a disease of complex genetics, even though individuals were all from family members with psychosis, rather than sporadic cases. Baohuoside I It is challenging to translate pluripotent cells into powerful disease models (Maury et al., 2012). For example, ESCs are limited by the availability of genetic screening and pre-implantation genetic diagnosis. For his or her part, iPSCs are potentially jeopardized by the methods of their generation; most cell lines published to date were produced by integrating vectors, although this will change as the effectiveness and predictability of non-integrating methods enhances. There are additional.