Recent advances in deriving induced pluripotent stem (iPS) cells from patients offer new possibilities for biomedical research and clinical applications, as these cells could be used for autologous transplantation. We differentiated iPS cells from patients with Parkinson's disease (PD) into dopaminergic (DA) neurons and show that these DA neurons can be transplanted without signs of neurodegeneration into the adult rodent striatum. The PD patient iPS (PDiPS) cellderived DA neurons survived at high numbers, showed arborization, and mediated functional effects in an animal model of PD as determined by reduction of amphetamine-and apomorphine-induced rotational asymmetry, but only a few DA neurons projected into the host striatum at 16 wk after transplantation. We next applied FACS for the neural cell adhesion molecule NCAM on differentiated PDiPS cells before transplantation, which resulted in surviving DA neurons with functional effects on amphetamine-induced rotational asymmetry in a 6-OHDA animal model of PD. Morphologically, we found that PDiPS cell-derived non-DA neurons send axons along white matter tracts into specific close and remote gray matter target areas in the adult brain. Such findings establish the transplantation of human PDiPS cell-derived neurons as a long-term in vivo method to analyze potential disease-related changes in a physiological context. Our data also demonstrate proof of principle of survival and functional effects of PDiPS cell-derived DA neurons in an animal model of PD and encourage further development of differentiation protocols to enhance growth and function of implanted PDiPS cellderived DA neurons in regard to potential therapeutic applications.

The cardinal motor symptoms of Parkinson's disease (PD) are caused by the vulnerability to dysfunction and degeneration of ventral midbrain (VM) dopaminergic (DA) neurons. A major limitation for experimental studies of current ES/iPS cell differentiation protocols is the lack of VM DA neurons with a stable phenotype as defined by an expression marker code of FOXA2/TH/β-tubulin. Here we demonstrate a combination of three modifications that were required to produce VM DA neurons. Firstly, early and specific exposure to 10 −8 M (low dose) retinoic acid improved the regional identity of neural progenitor cells derived from human ES cells, PD or healthy subjectspecific iPS cells. Secondly, a high activity form of human sonic hedgehog established a sizeable FOXA2 + neural progenitor cell population in vitro. Thirdly, early exposure to FGF8a, rather than Fgf8b, and WNT1 was required for robust differentiation of the FOXA2 + floor plate-like human neural progenitor cells into FOXA2 + DA neurons. FOXA2 + DA neurons were also generated when this protocol was adapted to feeder-free conditions. In summary, this new human ES and iPS cell differentiation protocol using FGF8a, WNT1, low dose retinoic acid and a high activity form of SHH can generate human VM DA neurons that are required for relevant new bioassays, drug discovery and cell based therapies for PD.

Teams are an integral component of quality improvement efforts in healthcare organizations. Quality improvement teams may involve persons either from the same or different disciplines. In either case, the selection of team members may be critical to the team's success. However, there is little research to guide selection of team members for quality improvement teams. In this paper, we use tools from social network analysis (SNA) to derive principles for the design of effective clinical quality improvement teams and explore the implementation of these principles using social network data collected from the inpatient general medicine services at a large academic medical center in Chicago, USA. While the concept of multidisciplinary teams focuses on the importance of the professional background of team members, SNA emphasizes the importance of the individual and collective connections of team members, both to persons outside the team and to each other. SNA also focuses on the location of individuals and groups between other actors in the flow of information and other resources within larger organizational networks. We hypothesize that external connections may be most important when the collection or dissemination of information or influence are the greatest concerns, while the relationship of team members to each other may matter most when internal coordination, knowledge sharing, and within-group communication are most important.