Secreted Noncoding RNAs and Therapeutic Neural Stem Cell Plasticity

Abstract Compelling evidence exists that somatic stem cell-based therapies protect the central nervous system (CNS) from chronic inflammation-driven degeneration, such as that occurring in experimental autoimmune encephalomyelitis (EAE), multiple sclerosis (MS) and cerebral ischemic/hemorrhagic stroke. However, while it was first assumed that stem cells may act through direct replacement of lost/damaged cells, it has now become clear that they are able to protect the damaged nervous system through a number of ‘bystander’ mechanisms other than cell replacement. In immune-mediated experimental demyelination and stroke – both in rodents and non-human primates – others and we have shown that transplanted neural stem/precursor cells (NPCs) possess a constitutive and inducible ability to mediate efficient ‘bystander’ myelin repair and axonal rescue. Yet a comprehensive understanding of the multiple mechanisms by which NPCs exert their therapeutic impact is lacking. We envisage that the remarkable therapeutic pl...