Stem cells in the treatment of neurodegenerative diseases (4)
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Parkinson's disease and stem cells
First described in 1817, Parkinson's disease – the second most common neurodegenerative disease [50] – is characterized by the death of dopaminergic neurons in the substantia nigra [51,52], which leads to deterioration of motor function. The pathological signs of this disease are the formation of Levi's bodies and neuritis, but its specific pathogenesis is still unclear [52]. Parkinson's disease itself is not fatal, but its complications can lead to death.
Currently, Parkinson's disease is treated medicinally and surgically. However, these methods are extremely symptomatic. Modern medical treatment of this disease consists in supplying the preserved dopaminergic neurons with the drug L-dopa, which they convert into dopamine [53]. However, such therapy is ineffective and, eventually, all dopaminergic neurons die [53].
The introduction of mesenchymal stem cells has been proposed as an alternative method of treating Parkinson's disease. Park et al. [54] tested the use of mesenchymal stem cells on a mouse model of Parkinson's disease and demonstrated the ability of these cells to significantly increase the number of preserved dopaminergic neurons and tyrosine hydroxylase-containing cells both in vitro and in vivo [54].
In another study, Murrell et al. [55] suggested using adult nasal stem cells of the olfactory epithelium to restore dopaminergic neurons in Parkinson's disease. Cells differentiated into nerve progenitor cells acquired the ability to transform into neurons similar to dopaminergic ones, both in vitro and in vivo [55].
The use of neural stem cells has also been considered as a potential treatment for Parkinson's disease. Yasuhara et al. [56] tested in vivo the possible positive effect of such cells on behavior, as well as their ability to protect neurons in Parkinson's disease. Immediate transplantation of nerve stem cells after administration of 6-hydroxydopamine (a neurotoxin that locally reduces the concentration of dopamine and is used to simulate Parkinson's disease in animals) into the brain of mice protected neurons containing tyrosine hydrolase and reduced the severity of symptoms of the disease [56].
The results of the study by Kim et al. [57] confirm the feasibility of introducing embryonic stem cells as replacement therapy. The authors have shown that mouse embryonic stem cells can produce an enriched population of neural stem cells of the midbrain. Dopamine neurons formed by such cells demonstrate electrophysiological and functional qualities characteristic of midbrain neurons [57]. In order to bring these experiments closer to practice, it is necessary to develop methods for enriching target cell populations and demonstrate that these cells perform functions that contribute to the cure of the disease.
Other studies have investigated the use of induced pluripotent stem cells (iPSCs) derived from mouse fibroblasts as a source of neural progenitor cells, which are multipotent adult stem cells, for subsequent administration to rats injected with 6-hydroxydopamine into brain tissue [58]. This procedure has demonstrated high efficiency, while the number of cells containing tyrosine hydroxylase has increased in almost all animals [58]. Iacovitti et al. [59] obtained similar results when using dopaminergic neurons of the midbrain grown from a commercially available line of human iPSCs IMR90, clone 4 [59]. After transplantation to rats with Parkinson's disease, modeled by the introduction of 6-hydroxydopamine, such cells not only survived, but also integrated into the animals' brains. However, it was shown that a large number of tumor–like cells expressing nestin, a protein typical of undifferentiated neural stem and semi-stem cells and at the same time a marker of aggressive breast cancer, remained in the injection zone [59]. The future success of such methods of replacement therapy for Parkinson's disease depends on the possibility of selecting safe cell lines for transplantation.
Continuation: amyotrophic lateral sclerosis and stem cells.
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30.03.2012