Deriviation of homogeneous population of oligodendrocytes from embryonic stem cells: Therapeutic implications for white matter repair in demyelinating diseases and traumatic brain injury.

摘要

There is a pressing need for new therapeutics for drug delivery and for the generation and transplantation of oligodendrocyte to the white matter to help replace and render injured cells that are lost in demyelinating disease and neurotrauma. Based on our current work, we have confirmed successfully that it is possible to direct mouse ES cells to become oligodendrocyte to a high degree of homogenity and reproducibility in our in vitro culture system. The novelty of our approach is that the media composition allows for the specific lineage progression of embryonic stern cells into neurospheres which give rise exclusively to oligodendroytes in timely fashion which mimics the in vivo development. These embryonic stem cell derived oligodendrocytes go on to myelinate rat dorsal root ganglia in vitro therefore showing that there is potential use of these cells in transplantation towards myelin repair.;In addition, a thorough understanding of the evolving pathophysiology of white matter injury in TBI is required to establish the most suitable targets for such treatments. We use controlled cortical impact (CCI) injury model, which has previously been shown to produce a precise injury as indicated by experiments titrating impact velocity and depth with injury severity (Dixon, Clifton et al. 1991). We use controlled cortical impact (CCI) injury model, which has previously been shown to produce a precise injury as indicated by experiments titrating impact velocity and depth with injury severity (Dixon, Clifton et al. 1991). While some of the cellular responses that occur after CCI have been presented separately before, the findings we report here describe the evolution of white matter damage and oligodendrocyte pathologies that occur after injury and the spatiotemporal relationship between them. We present especially novel findings on the neural stem cell and oligodendrocyte progenitor response after CCI injury model (Tong, Igarashi et al. 2002; Chen, Pickard et al. 2003; Marklund, Bakshi et al. 2006; Conte, Raghupathi et al. 2008).