One of the most impressive natural mechanisms is regeneration, which is the process of replacing or repairing damaged cells, tissues, and organs. Its potential medical applications include the treatment of a wide range of injuries and diseases, including Parkinson's disease (PD) (NIH, 2020). Parkinson's disease is the world’s second most prevalent neurodegenerative disease, behind Alzheimer's disease, with an incidence of 1% and 5% in people over 65 (Xiao et al,2020). According to the Parkinson Foundation, 60,000 people in America are diagnosed with Parkinson per year. The pathogenesis of Parkinson's disease is caused by the loss of dopaminergic neurons within the substantia nigra pars compacta (SNpc), the main function of which is the movement of the person, and most dopaminergic neurons are found there that ends up during a significant decline in dopamine content in the striatum (Xiao et al.,2021). The apparition of tremor, rigidity, slowness of body movements (bradykinesia), and other symptoms that lower the quality of life of a patient is because of the loss of these neurons that causes the disease's most well-known symptoms of PD.
In this sense, regenerative medicine is studied intensively to restore dopamine levels in the striatus through developing techniques that could restore the complete nigrostriatal pathway, an essential step to reconnect the feedback pathways to maintain adequate dopamine regulation. One of these alternatives is cell replacement, which uses both endogenous and exogenous cell sources, including stem cells, to generate the secretion of neuroprotective factors, as well as self-renewing cells. Of all the stem cell types, pluripotent stem cells are one of the best options for use in tissue implants (grafts), as they provide a massive source of any cell type, leading to neuronal reprogramming. This could provide autologous dopaminergic neurons reprogrammed from the patient's own somatic cells (Harris et al., 2020).
In addition, it is important to use a cell-based strategy with scaffolds because it could allow extending endogenous regeneration or could generate the replacement of neural cells and circuits. Since most of these scaffolds in PD aim to promote an adequate environment for the implanted cells, neuron regeneration will be improved, and meanwhile, the preformed constructs could act as functional relay transmitters to transmit signals between disconnected cells (Harris et al., 2020).
Micro-TENNs is one of the most recent advances in computational modeling. These are 3-D living constructions that simulate the neuroanatomy of the white matter pathways within the brain and are developed as implantable micro-tissue for the reconstruction of the axonal tract which is the way for the dopaminergic neurons (Marinov et al., 2020). Replacing dopaminergic neurons in the SNpc could allow the neurons add up inputs before the generation of a nerve impulse (synaptic integration) with SNpc inputs, and restoring the end of the neuron (axon terminations) in the striatum (caused the motor symptoms in PD) that will restore the loss of nigrostriatal circuits due to PD.
Therefore, the goal of these research studies are to “replace the nigrostriatal pathway with all the recent technology —dopaminergic neurons in the SNpc and their axonal projections to the striatum—thereby allowing implanted cells /tissue to be subject to the normal cellular regulation that dopaminergic SNpc neurons and restore this crucial circuit for motor control feedback” (Harris et al.,2020).
Although regenerative medicine may give an advanced treatment option, non-motor symptoms of Parkinson's disease and other restrictions remain a challenge. However, this new therapy has potential in the future because the danger of immunological rejection in patients is decreasing. Neuroregeneration research in cells would most likely be dependent on the complexity of the patient's clinical condition and, with it, the complexity of the degree of neurodegeneration, which could generate a precise and efficient treatment for each patient.
About the Author
Violeta F. Vilcapoma Torres is a freshman at Universidad Peruana Cayetano Heredia studying Biomedical Engineering.
References
Harris, J. P., Burrell, J. C., Struzyna, L. A., Chen, H. I., Serruya, M. D., Wolf, J. A., Duda, J. E., & Cullen, D. K. (2020). Emerging regenerative medicine and tissue engineering strategies for Parkinson’s disease. NPJ Parkinson’s Disease, 6(1), 4. https://doi.org/10.1038/s41531-019-0105-5
Wang, N. B., Beitz, A. M., & Galloway, K. (2020). Engineering cell fate: Applying synthetic biology to cellular reprogramming. Current Opinion in Systems Biology, 24, 18–31. https://doi.org/10.1016/j.coisb.2020.09.002
Marinov, T., López Sánchez, H. A., Yuchi, L., Adewole, D. O., Cullen, D. K., & Kraft, R. H. (2020). A computational model of bidirectional axonal growth in micro-tissue engineered neuronal networks (micro-TENNs). In Silico Biology, 14(1–2), 85–99. 10.3233/ISB-180172
Parmar, M., Grealish, S., & Henchcliffe, C. (2020). The future of stem cell therapies for Parkinson disease. Nature Reviews. Neuroscience, 21(2), 103–115. https://doi.org/10.1038/s41583-019-0257-7
Xiao, Z., Lei, T., Liu, Y., Yang, Y., Bi, W., & Du, H. (2021). The potential therapy with dental tissue-derived mesenchymal stem cells in Parkinson’s disease. Stem Cell Research & Therapy, 12(1), 5. https://doi.org/10.1186/s13287-020-01957-4
In this sense, regenerative medicine is studied intensively to restore dopamine levels in the striatus through developing techniques that could restore the complete nigrostriatal pathway, an essential step to reconnect the feedback pathways to maintain adequate dopamine regulation. One of these alternatives is cell replacement, which uses both endogenous and exogenous cell sources, including stem cells, to generate the secretion of neuroprotective factors, as well as self-renewing cells. Of all the stem cell types, pluripotent stem cells are one of the best options for use in tissue implants (grafts), as they provide a massive source of any cell type, leading to neuronal reprogramming. This could provide autologous dopaminergic neurons reprogrammed from the patient's own somatic cells (Harris et al., 2020).
In addition, it is important to use a cell-based strategy with scaffolds because it could allow extending endogenous regeneration or could generate the replacement of neural cells and circuits. Since most of these scaffolds in PD aim to promote an adequate environment for the implanted cells, neuron regeneration will be improved, and meanwhile, the preformed constructs could act as functional relay transmitters to transmit signals between disconnected cells (Harris et al., 2020).
Micro-TENNs is one of the most recent advances in computational modeling. These are 3-D living constructions that simulate the neuroanatomy of the white matter pathways within the brain and are developed as implantable micro-tissue for the reconstruction of the axonal tract which is the way for the dopaminergic neurons (Marinov et al., 2020). Replacing dopaminergic neurons in the SNpc could allow the neurons add up inputs before the generation of a nerve impulse (synaptic integration) with SNpc inputs, and restoring the end of the neuron (axon terminations) in the striatum (caused the motor symptoms in PD) that will restore the loss of nigrostriatal circuits due to PD.
Therefore, the goal of these research studies are to “replace the nigrostriatal pathway with all the recent technology —dopaminergic neurons in the SNpc and their axonal projections to the striatum—thereby allowing implanted cells /tissue to be subject to the normal cellular regulation that dopaminergic SNpc neurons and restore this crucial circuit for motor control feedback” (Harris et al.,2020).
Although regenerative medicine may give an advanced treatment option, non-motor symptoms of Parkinson's disease and other restrictions remain a challenge. However, this new therapy has potential in the future because the danger of immunological rejection in patients is decreasing. Neuroregeneration research in cells would most likely be dependent on the complexity of the patient's clinical condition and, with it, the complexity of the degree of neurodegeneration, which could generate a precise and efficient treatment for each patient.
About the Author
Violeta F. Vilcapoma Torres is a freshman at Universidad Peruana Cayetano Heredia studying Biomedical Engineering.
References
Harris, J. P., Burrell, J. C., Struzyna, L. A., Chen, H. I., Serruya, M. D., Wolf, J. A., Duda, J. E., & Cullen, D. K. (2020). Emerging regenerative medicine and tissue engineering strategies for Parkinson’s disease. NPJ Parkinson’s Disease, 6(1), 4. https://doi.org/10.1038/s41531-019-0105-5
Wang, N. B., Beitz, A. M., & Galloway, K. (2020). Engineering cell fate: Applying synthetic biology to cellular reprogramming. Current Opinion in Systems Biology, 24, 18–31. https://doi.org/10.1016/j.coisb.2020.09.002
Marinov, T., López Sánchez, H. A., Yuchi, L., Adewole, D. O., Cullen, D. K., & Kraft, R. H. (2020). A computational model of bidirectional axonal growth in micro-tissue engineered neuronal networks (micro-TENNs). In Silico Biology, 14(1–2), 85–99. 10.3233/ISB-180172
Parmar, M., Grealish, S., & Henchcliffe, C. (2020). The future of stem cell therapies for Parkinson disease. Nature Reviews. Neuroscience, 21(2), 103–115. https://doi.org/10.1038/s41583-019-0257-7
Xiao, Z., Lei, T., Liu, Y., Yang, Y., Bi, W., & Du, H. (2021). The potential therapy with dental tissue-derived mesenchymal stem cells in Parkinson’s disease. Stem Cell Research & Therapy, 12(1), 5. https://doi.org/10.1186/s13287-020-01957-4
