Neurodegenerative disease is a broad term encompassing a number of chronic, progressive diseases that result in degeneration and or death of neurons; these diseases include Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS) and affect over 50 million Americans each year[1][2].
Since neurons possess a very limited ability to reproduce and/or replace themselves, any damage to these cells tends to be permanent and contributes to incurable and progressive debilitating conditions affecting physical movement and mental function.
While research has determined that these neurodegenerative diseases are primarily a result of the accumulation of misfolded proteins in the brain, the specific cause of these conditions remains unknown; additionally, the complexity of these conditions often lead to delayed diagnosis, most often a result of the lack of effective and recognizable biomarkers. To date, no preventative treatment for these conditions exist and any current treatment serves to only delay the progression of the disease, most often with poor results.
In this article, Yao et al. explore the viability of using mesenchymal stem cells (MSCs) as cell replacement therapy for treating neurodegenerative diseases. According to the authors, MSCs demonstrated the ability to self-renew and differentiate coupled with their relative ease of collection, isolation, and ability to culture and their immunoregulatory properties make them a promising potential treatment option.
Although the specific therapeutic mechanisms of MSCs in the treatment of neurodegenerative diseases are still being studied, they have shown potential in three specific areas: homing, paracrine, and immunoregulation.
Homing involves MSCs ability to spontaneously migrate to damaged regions of the body, making them a viable therapeutic treatment option – especially as a carrier of therapeutic drugs. It is hypothesized that MCS’s ability to home should allow drugs to be attached and to pass through the blood-brain barrier to be delivered to locations in the CNS and brain that are affected by neurodegenerative diseases.
Paracrine, or paracrine signaling, is a cell’s ability to release hormones that communicate with the cells in its vicinity. MSCs ability to secrete growth factors, cytokines, chemokines, and various enzymes are important aspects of cell migration and immune regulation. Animal studies have demonstrated using MSC-derived exosomes to improve symptoms associated with muscle atrophy translates into a promising clinical treatment strategy for neurodegenerative diseases.
MSCs are undifferentiated precursor stem cells with low immunogenicity. Researchers attribute the immunoregulation of MSCs to their various interactions with T cells, B cells, and natural killer cells. Animal studies have shown that placental-derived MSCs have demonstrated beneficial effects, particularly in mice with AD; researchers hypothesize that this effect is a result of these MSCs inhibiting the release of inflammatory cytokines, preventing cognitive impairments, and increasing the survival rate of neurons and nerve regeneration. These findings have demonstrated the potential for immunosuppressants, in combination with MSCS, to be used in future clinical treatments of neurodegenerative diseases.
After reviewing numerous in vitro and in vivo experiments in animal models, the researchers have confirmed the potential therapeutic benefits of MSCs as well as their safety and effectiveness in a wide variety of therapeutic applications. Additionally, studies have also demonstrated no serious or concerning adverse reactions associated with clinical trials (both human and animal) using MSCs from autologous or allogeneic sources.
However, Yao et al. caution that as therapies using MSCs continue to develop, so too should the process used for preparing MSCs as well as that used for determining ideal method and dose for patients; taking these steps will contribute to a deeper understanding of MSCs potential when used as a therapeutic treatment for neurodegenerative diseases.
Source: (2020, July 20). Mesenchymal Stem Cells: A Potential … – Karger Publishers. Retrieved from https://www.karger.com/Article/Fulltext/509268
[1] “What? | JPND.” https://www.neurodegenerationresearch.eu/what/.
[2] “Neurodegenerative Diseases: An Overview of … – NCBI – NIH.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280411/.
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