Induced pluripotent stem cells: therapeutic potential for multiple sclerosis

Multiple Sclerosis (MS) is a devastating disease of the central nervous system characterized by loss of the insulating myelin layer around axons due to inflammatory attacks. Loss of myelin in MS not only disrupts the rapid signal transmission along axons, but also deprives axons of essential nutrition and protection provided by myelin. Prolonged absence of such protection makes axons vulnerable to all kinds of toxic environmental influences, eventually leading to degeneration of neurons provoking the most severe neurological deficits in MS. Reducing or preferably completely preventing neurodegeneration in MS is the main challenge for new treatment methods; establishing fast restoration of the myelin sheaths (remyelination) seems a logical and appropriate approach. However, while considerable progress has been made in recent years in therapies that can significantly reduce the severity and frequency of inflammatory attacks in MS patients, there is no therapeutic strategy for MS aimed at the efficient remyelination of axons. Intracerebral transplantation of myelin-forming cells – oligodendrocytes – has been shown a successful approach in various animal models of MS. However, such an approach was not possible for MS patients because of the lack of a suitable source of autologous (“own”) oligodendrocytes. The solution to this problem was provided by the development of induced pluripotency in 2006: ordinary somatic cells, like skin fibroblasts, could be reprogrammed into so-called induced pluripotent stem cells (iPSCs), embryonic stem cell-like cells with the capacity to proliferate unlimitedly and to differentiate into any cell type of the body. iPSCs can thus serve as a virtually inexhaustible autologous source for transplantable myelin-forming cells. This thesis describes research on the potential of iPSCs as a source for oligodendrocytes for novel cell-based remyelination and neuroprotection therapy of MS.

Dissertation: http://irs.ub.rug.nl/ppn/387257187