It will also aid in identifying new ways to stimulate endogenous stem and progenitor cells, e.g., with small-molecule mimics of instructive factors that can

lead to controlled in vivo cell expansion and differentiation. In terms of cell transplantation for replacement, in addition to achieving routine and standardized protocols for hundreds of specific CNS cell types, we anticipate further genetic manipulation of cells prior to transplantation to correct genetically based diseases or combat the disease process. As well as directed single-gene excision or supplementation, the ability to alter networks and pathways via targeting noncoding RNAs and RNA binding proteins is another exciting BIBW2992 molecular weight avenue with great potential. Combination therapies that take into account the specific cell-cell and cell-matrix

interactions that are crucial for CNS function are an active area of research. One promising option is to employ scaffolding along with stem cells to provide a substrate and functionalized artificial niche to direct stem cell behavior (Keung et al., 2010). Expanding on this idea, CNS repair may be better achieved by transplantation of functional units that take into account the interdependence of different CNS cell types, maintaining key interactions such as endothelial cells and neural GSK1349572 cells to improve graft vascularization, neurons, and glial cells or different neuron types to replace multiple elements of damaged circuits, perhaps in three-dimensional arrangements, as dramatically demonstrated by mouse ES-derived eye cup formation (Eiraku et al.,

2011). Medical advances require a permissive environment to reach patients, and Histamine H2 receptor progress in regulatory science will be critical to enable successful, efficient translation. Current regulatory paradigms are of variable stringency depending upon global region and continue to evolve with scientific progress. Failure to conduct trials under strict regulatory oversight can increase risk to patients and the stem cell field in general. Sobering examples of isolated reports of adverse events in patients exploring so-called “stem cell tourism” include a young patient with ataxia telangiectasia given multiple CNS injections of unpurified and uncharacterized mixtures of fetal-derived NSCs from multiple donors over several years that led to donor cell tumor growth (Amariglio et al., 2009). This emphasizes the need to conduct such trials under suitable regulatory and ethics oversight. One controversial issue is that regulatory clearance can be given in the absence of peer-reviewed publication of the relevant preclinical data, which precludes full scrutiny and replication of stem cell culture protocols and results by the broader research community. It should be underscored that the IND review process provides in-depth peer-review scrutiny through ad hoc consultants available to both regulatory and ethics bodies.