Rationale for the use of neural stem/precursor cells in immunemediated demyelinating disorders

摘要

The adult mammalian brain harbours multi-potent stem/precursor cells supporting self-renewal and differentiation within specialised niches, namely the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus. In response to different environmental cues, these neural stem/precursor cells (NPCs) may differentiate into neurons, astrocytes or oligodendrocytes. Due to their intrinsic plasticity, these cells are considered an attractive therapeutic tool for the treatment of several neurological disorders. We have shown that syngenic NPCs, injected systemically in mice with chronic central nervous system (CNS) inflammation, reduce tissue damage and improve functional recovery. NPCs express constitutively activated integrins, which enable them to enter the CNS. Once in the site of tissue injury, transplanted NPCs promote brain repair through several mechanisms of action. They can induce apoptosis of CNS-infiltrating T cells as well as foster remyelination driven by endogenous oligodendrocyte progenitors. Neuroprotective and immunomodulatory molecules released principally from undifferentiated NPCs at the site of tissue damage mediate these effects. This bystander (or paracrine) ability of transplanted NPCs to protect the CNS from different types of injury suggests that such therapeutic procedure could be of great interest in the future therapeutic armamentarium of inflammatory demyelinating diseases of the CNS.