論文

Neural stem cells(NSCs) are multipotential progenitor cells that can generate neurons, astrocytes, and oligodendrocytes, the three major cell types in the central nervous system. Due to their self-renewal activities, NSCs can proliferate in an undifferentiated state in vitro, allowing them to be expanded mitotically and harvested in bulk. Recent advances in stem cell biology have led us to investigate methods for the regenerative manipulation of the damaged CNS. However, there is much that is still not known about regulatory mechanisms of the differentiation and self-renewal of NSCs. In this article, we review some of the basic notions regarding the extracellular factors and signal transduction cascades involved in the differentiation and maintenance of NSCs.

One of the final goals of our research is the regaining of normal functions previously lost in damaged tissue. While it has long been believed regeneration of the central nervous system was absolutely impossible, scientists have recently made progress towards this goal. For the regeneration of damaged tissues, both morphological and functional reconstitutions are an indispensable process. As undifferentiated cells, have better survival rates in all types of environments as well as better competency with regard to extracellular signaling factors, we have tried to take advantage of these characteristics. We are trying to find methodologies that will let these cells recapitulate the developmental processes in order to regain the normal physiological functions of damaged tissues. Some of the candidate cells that can be utilized for retinal regeneration are retinal stem cells and embryonic stem cells. In this study, we describe a method for inducing these cells towards specific cell fates as well as their potential therapeutic application. We also describe the significance of investigating the effects of the microenvironment in damaged retina for the purpose of inducing neural retinal regeneration.

It had been long believed that our adult mammalian central nervous system (CNS) does not regenerate after damage due to injuries or degenerative diseases, as Santiago Ramóny Cajal had indicated long time ago. Today, however, CNS came to be recognized as an important target of so called "regenerative medicine". We have been proposing that regeneration of CNS does include the following three concepts: i) re-growth of the damaged neuronal axons, ii) replenishment of lost neural (or neuronal) cells and iii) recovery of lost neural functions. Here, we would like to emphasize that to recapitulate normal neural development is an essential strategy for CNS-regeneration. In this review, we would like to take Parkinson's disease and spinal cord injury as examples to discuss actual strategy aiming for CNS-regeneration.