By Robert Kim

Parkinson’s Disease (PD), one of the most prominent neurodegenerative disorders, is a chronic neurological disorder where progressive degeneration of the nervous system manifests primarily as loss of control of the body’s motor system.

The typical physical symptoms of PD consist of resting tremor, muscular rigidity, and hypokinesia (slowness of movement). The pathology behind the motor symptoms of PD is the progressive loss of mesencephalic dopaminergic neurons of the midbrain. Midbrain dopaminergic neurons are the main source of dopamine for the central nervous system. The loss of these neurons disrupts the function of the nigrostriatal system – the dopamine pathway responsible for movement (Weinert et al., 2015).

Current treatments for PD are based around compensating for the loss of dopamine signal transmission. One treatment example is the prescription of L-3, 4-dihydroxyphenylalanine (L-DOPA) – a direct chemical precursor to dopamine prescribed as a supplement to the patient in order to increase dopamine levels. Another treatment is the prescription of dopamine agonists, which are able to activate dopamine receptors, and thus relay motor signals in the dopamine pathways in the absence of dopamine itself. An invasive but effective treatment is deep brain stimulation, where a medical device is surgically implanted to deliver electrical impulses to parts of the brain to stimulate specific parts of the brain. Although these treatments can be effective, they do not fix the original problem of dopaminergic neuron loss, but rather circumvent the original problem.

A solution to directly solve the problem of the decreasing population of midbrain dopaminergic neurons involves the transplantation of mesencephalic tissue. Initial experimental trials consisted of embryonic mesencephalic tissue transplantation into the striatum of animal models of PD, which led to successful restoration of dopamine signal transmission in the striatum (Lindvall & Kokaia, 2009). However, the efficacy of these transplantations in human trials was significantly lower. Not only is the cell material itself scarce in availability, but even so, the lack of standardization of the cell material leads to inadequate cell survival rates and inconsistent results.

In solution to the problems prevalent in human cell transplantation, stem cells have shown promise in the possibility of mass producing standardized dopamine neurons for successful grafting. Specifically, human induced pluripotent stem (iPS) cells have recently been established as being the most robust source of patient-specific neuron generation. Human induced pluripotent stem (iPS) cells are derived from matured adult tissue instead of embryonic tissue, and can be converted to neuronal cells with dopaminergic properties at an accelerated rate compared to other stem cells.

The significant improvement in efficacy in the grafting of these iPS cells comes primarily from the complement utilization of structural support to allow neurons to generate in three-dimensional configurations. Electrospun synthetic polymer fibers can be used to build three-dimensional biomaterial scaffolds that provide support to iPS cells during transplantation (Carlson et al., 2016). The support of these 3D scaffolds has exhibited improved success of cell engraftment and increased survival of the transplanted neuron cells due to the ability of the converted stem cells to associate with the native recipient environment in a more organic 3D configuration. In animal trials, the coupling of iPS cells with this 3D scaffold biotechnology results in cell survival rates over 2 orders of magnitude compared to other cell transplantation methods, which makes this the leading protocol in the treatment of PD.

References

1. Carlson, A. L., Bennett, N. K., Francis, N. L., Halikere, A., Clarke, S., Moore, J. C., & Moghe, P. V. (2016). Generation and transplantation of reprogrammed human neurons in the brain using 3D microtopographic scaffolds. Nature Communications, 7, 10862.

2. Lindvall, O. & Kokaia, Z. (2009). Prospects of stem cell therapy for replacing dopamine neurons in parkinson's disease. Trends in Pharmacological Sciences, 30(5), 260-267.

3. Weinert, M., Selvakumar, T., Tierney, T., & Alavian, K. (2015). Isolation, culture and long-term maintenance of primary mesencephalic dopaminergic neurons from embryonic rodent brains. Jove-Journal of Visualized Experiments, (96).