The axonal connections between neurons are sheathed in myelin, which acts as an insulator to enable the propagation of electrical impulses along the axon. Like all molecular structures in the body and brain, myelin sheathing is subject to ongoing damage and must continually be maintained in order to prevent dysfunction in the nervous system. A population of cells known as oligodendrocytes undertakes this task. Conditions in which excessive loss of myelin occurs, such as the autoimmune condition multiple sclerosis, are particularly debilitating. But a lesser degree of myelin damage occurs to everyone in old age, in part due to reduced oligodendrocyte function, and this damage contributes to cognitive impairment.
Thus it is interesting to keep an eye on that part of the research community focused on dymelinating conditions such as multiple sclerosis. It is plausible that future therapies capable of achieving at least some degree of remyelination in patients with severe demyelination could also help to restore meylin loss in aged individuals - it all depends on the fine details. Therapies that compensate for damage and dysfunction by increasing oligodendrocyte activity will probably be effective in both aged individuals and patients with multiple sclerosis, while curative therapies that directly address the autoimmune causes of multiple sclerosis will likely be of little use in aged individuals.
Delivering neural stem cells into the brain has been tested as a therapy of many forms of neurodegeneration, at least in animal models. Bringing this sort of therapy into human trials has progressed very slowly indeed over recent decades, with ongoing programs of research and development largely focused on Parkinson's disease while the state of the art advanced from fetal cells to embryonic stem cells to induced pluripotent stem cells. Today's open access paper is an example of the more broad application of neural stem cells in animal models, in which the transplanted cells induce remyelination to repair severe damage to myelin sheathing in the brain.
Remyelination of chronic demyelinated lesions with directly induced neural stem cells
The limited ability of central nervous system (CNS) progenitor cells to differentiate into oligodendrocytes limits the repair of demyelinating lesions and contributes to the disability of people with progressive multiple sclerosis (PMS). Neural stem cell (NSC) transplantation has emerged as a safe therapeutic approach in people with PMS, where it holds the promise of healing the injured CNS. However, the mechanisms by which NSC grafts could promote CNS remyelination need to be carefully assessed before their widespread clinical adoption.
In this study, we used directly induced NSCs (iNSCs) as a novel transplantation source to boost remyelination in the CNS. Using a mouse model of focal lysophosphatidylcholine (LPC)-induced demyelination, we found that mouse iNSCs promote remyelination by enhancing endogenous oligodendrocyte progenitor cells differentiation and by directly differentiating into mature oligodendrocytes. Transplantation of mouse iNSCs in LPC-lesioned Olig1 knockout mice, which exhibits impaired remyelination, confirmed the direct remyelinating ability of grafts and the formation of new exogenous myelin sheaths. We also demonstrated that the xenotransplantation of human iNSCs (hiNSCs) is safe in mice, with hiNSCs persisting long-term in demyelinating lesions where they can produce graft-derived human myelin.
Our findings support the use of NSC therapies to enhance remyelination in chronic demyelinating disorders, such as PMS.
View the full article at FightAging
