Can mesenchymal stem cells reduce vulnerability of dopaminergic neurons in the substantia nigra to oxidative insult in individuals at risk to Parkinson's disease?

Abstract

PD (Parkinson's disease) is characterized by the selective loss of DA (dopaminergic) neurons in the substantia nigra of the midbrain region, but not in the ventral tegmental area and other catecholaminergic cell group areas. The aetiology of PD is attributed both to environmental and genetic causes, and certain population of individuals may be classified as at risk of developing PD later in life. However, there are as yet no therapy regimens that can help to delay or prevent the onset of the disease to realize long-term benefits from this early diagnosis. In PD, a vicious cycle gets initiated in the substantia nigra, because of which susceptible neurons continue to degenerate whereas damaged neurons do not get enough support for regeneration. This happens primarily because of the local environment of oxidative damage brought about by the dual presence of dopamine and high levels of iron, decline in cellular detoxification systems and low density of glial cells surrounding the DA neurons in the mesencephalic region. To enhance the defence mechanism of the substantia nigra in this situation, it is necessary to combat the oxidative insult while providing trophic factors for the survival and regeneration of the damaged neurons. In light of in vitro and in vivo studies, MSCs (mesenchymal stem cells) as candidates for cell-based therapies in PD have greater scope than as mere replacement of cell type, since they can be used as a cellular system for the detoxification of ROS (reactive oxygen species) as well as a supplier of neurotrophic factors to modulate the local environment. Building on progress in unravelling the multipronged effect of MSCs, we therefore hypothesize that MSCs could be used as a prophylactic strategy to delay or prevent the onset of PD in at-risk individuals, and to slow down the progression of the disease.