Editorial [Hot Topic: Neural Stem Cell Therapies in Treating Neurological Diseases in Adult Brain (Guest Editor: Kunlin Jin)]

摘要

Correct diagnosis and effective treatment of diseases are two essential tasks for a clinical doctor. With advancing technology, the early and correct diagnosis of diseases is getting easier; however, the treatment of most diseases remains one of the biggest challenges for clinical medicine in 21st century. Broadly speaking, the causes of human diseases can be classified into two categories: abnormal cell death and abnormal cell proliferation. Examples of the former are Alzheimer disease and stroke, both of which cause cell death in the brain. Cell death in different locations produces different diseases. For example, Parkinson disease prdouces death of cells in the substantia nigra, whereas Alzheimer disease prominently affects the hippocampus and cerebral cortex. Abnormal cell proliferation is a feature of cancer. Recent studies show that cancer is initiated from cancer stem cells. In theory, if we can find an approach to kill cancer stem cells, we can cure cancer, and if we can induce stem cells to differentiate into mature cells such as neurons, we will be able to replace damaged neurons for therapy of neurodegenerative diseases. Hence, stem cells are important medically both because of the risk they pose in carcinogenesis, and for the potential they offer for tissue regeneration or replacement.nnStem cells can be classified into embryonic stem cells (ESCs), derived from blastocysts, and adult stem cells, which are found in adult tissues. Both have two important characteristics that distinguish them from other types of cells. First, they are unspecialized cells that are able to renew themselves through mitotic cell division. The second is that under certain conditions, they can differentiate into a diverse range of specialized cell types. Pluripotent ESCs can form cells of all tissues of the adult organism and adult stem cells have generally been regarded as having the capacity to form only the cell types of the organ in which they are found; however some adult stem cells may exhibit multipotency.nnAlthough human ESCs, which were first generated from human embryos in 1998, hold immense potential for therapeutic use in cell therapy, they also have disadvantages. This is evident in the proposed use of such cells to treat neurological diseases by intracerebral transplantation. First, surgical transplantation may result in local tissue damage or stroke. Second, the use of human ESCs is ethically and politically controversial. Third, neural degeneration in some CNS diseases is extensive, multifocal or even global, which may require widespread replacement beyond the capabilities of surgical transplantation. Finally, intracerebral transplantation may be associated with adverse effects related to the unregulated function of ectopic tissue.nnIt was thought for some time that the brains of adult mammals do not generate new neurons, although Altman first observed the proliferative potential of adult rodent brain in the 1960s. After years of debate, it is now accepted that neural stem cells are present in the rostral subventricular zone (SVZ) surrounding the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) in adult mouse, rat, non-human primate and human brain. Newly generated cells in the SGZ can differentiate into mature, functional neurons and integrate into the DG as granule cells, which are involved in memory formation in normal brain. More interestingly, endogenous neural stem cells in these discrete regions proliferate in response to brain injuries such as stroke and neurodegerative diseases such as Huntington's diseases. These disease-induced newborn cells can migrate into damaged brain regions, where they differentiate into mature neuronal cells. Therefore, it might be possible for damaged cells to be replaced from endogenous neural stem cell pools. However, the innate capacity for brain repair appears to be limited......