Even if the routine sampling of neurons directly from patients were possible, an inability to expand and study these postmitotic cells in vitro for prolonged periods would further diminish their utility. However, recent advances in the areas of stem cell and reprogramming biology now seem to provide a novel route to the generation of a wide variety of neural types for studying neurological disease. New “stem cell” models of disease provide an emerging and exciting opportunity to test Feynman’s assertion of whether or not we “understand” enough concerning the underlying causes of neurological disease to accurately “create” neurodegenerative processes in vitro. Here we review emerging efforts
to use stem cell and reprogramming approaches to produce specific human neural subtypes Ruxolitinib manufacturer carrying patient genotypes as well as initial attempts to monitor these neurons for hallmarks of disease-specific degenerative Lonafarnib in vivo processes. As we will describe, when stem cells are combined with methods that direct their differentiation along the lineages leading to the neuronal types principally affected in a given neurological disease, this new resource now provides exciting opportunities for disease modeling,
drug discovery, predictive toxicology, and transplantation therapy (Figure 1). The implicit promise of this technology is that patient-derived iPS cells may offer unprecedented opportunities to study the developmental progression of a neurological disease process in vitro. While the full potential of this approach is only beginning to be realized, initial attempts to use it for the modeling of several neurological disorders have provided the proof of principle that further insight into more complex disorders may be possible. Human pluripotent stem cells are characterized by Chlormezanone the ability to renew indefinitely in culture while retaining their capacity to differentiate into most, if not all, cell types (Yu and Thomson, 2008). This differentiation potential includes the ability to produce previously inaccessible cell types from the nervous system, which has obvious
implications for the study and treatment of neurological disease. Human embryonic stem (hES) cells are pluripotent stem cells derived from the inner cell mass of the blastocyst-stage embryo. These preimplantation embryos generally exist in excess of clinical need at in vitro fertilization (IVF) clinics and are donated to research by individuals under informed consent (Chen et al., 2009, Cowan et al., 2004 and Thomson et al., 1998). Of particular interest for the study of neurological disease are stem cell lines produced from embryos discarded after preimplantation genetic diagnosis (PGD) because they were identified to carry disease-associated mutations. Such stem cell lines would in turn be expected to carry the disease genes responsible for the condition and could prove useful for mechanistic studies.