Neurodegenerative diseases affect over 50 million Americans each year and occur as a result of nerve cells in the brain, peripheral nervous system, and the central nervous system slowly and progressively losing function before eventually dying[1].
While significant progress has been made in identifying mechanisms and risk factors contributing to the cause and development of these various neurodegenerative diseases, evidence continues to indicate that many of these conditions are influenced by oxidative stress. Research has also shown that antioxidants, the only strategy used to address this mechanism to date, have been demonstrated to be ineffective and, in some instances, even causing additional side effects.
In addition, although progress has been made in the overall understanding and management of several side effects associated with conditions contributing to neurodegeneration and that multifactor intervention introduced at an early stage is believed to be most successful, research has yet to identify a way to slow the progression of these debilitating conditions.
As part of this review, Angeloni et al. provide an analysis of recent literature examining the role of oxidative stress in several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, ALS, retinal ganglion cells, and ataxia. The authors also discuss the emerging role of mesenchymal stem cells (MSC) and their potential in fighting oxidative stress and enhancing antioxidant capacity and neurotrophin expression.
Recent literature concludes that oxidative stress has a significant role in each of the neurodegenerative diseases mentioned above. Specifically, oxidative stress has been found to:
Play a fundamental role in Alzheimer’s disease, affecting different pathways involved in AD brain cells.
Have a causal role and also be a result of different pathologies in PD.
Be both a cause and consequence of impaired function related to ALS.
Be a significant cause of damage in a number of ocular neurodegenerative diseases, including diabetic retinopathy, glaucoma, and retina ischemia-reperfusion injury.
Increase ROS production linked to mitochondrial dysfunction in ataxia cell models.
The literature also indicates that MSC therapy can be a promising future management tool for neurodegenerative disease that enhances antioxidant capacity, increases neurotrophin expression, inhibits pro-inflammatory cytokine secretions, and counteracts microglial ROS production.
However, the authors also conclude that while the role of MSCs in counteracting oxidative stress-related neurodegeneration, additional studies demonstrating a more neurodegenerative disease-specific therapeutic MSC strategy for preventing a broad range of previously mentioned disorders are needed.
Accordingly, these future studies will be useful in helping to discover the appropriate numbers of MSCs needed for transplantation, realize optimal timing of transplantation, identify the correct disease stage for transplantation, and better understand the safety, functionality, recovery, and motor and cognitive improvements of various MSCs used in this process.
In neurodegenerative conditions and cases of brain damage such as traumatic brain injury (TBI), the goal of treatment is usually to manage symptoms and prevent or slow the rate of further damage. Yet, ongoing research suggests stem cells could play an important role in creating new neurons, potentially resulting in repair of central nervous system damage and potentially regrow brain tissue. While the science is still in its infancy, there is evidence to suggest stem cell therapy could help to potentially restore lost brain function.
Just until a couple decades ago, scientists were under the impression that the brain and spinal cord could not rebuild themselves once cells were lost. Yet, in the mid-1990s, neuroscientists discovered that the brain could create new neurons in certain circumstances, which arise from neural stem cells. As undifferentiated cells, the stem cells could give rise to many different brain cell types, including neurons, which carry messages throughout the nervous system.
Further research has supported the idea that neurons can regenerate. For instance, in 2003, research was published which showed improvements in paralyzed rats who were exposed to a virus which caused symptoms similar to that of amyotrophic lateral sclerosis (ALS). Mice that had been previously paralyzed were able to regain some mobility after receiving stem cell injections, and the stem cells took on the characteristics of mature motor neurons.
Researchers have also been exploring stem cell therapies to help treat Parkinson’s disease. The goal is to rebuild the central nervous system through stem cell implantation. While levodopa is the go-to treatment to help regulate dopamine levels which are affected in PD, the drug’s efficacy tends to wear off over time, and its side effects increase. Some researchers have investigated the use of fetal stem cell tissue for PD patients, but lack of standardization and challenges in acquiring donor tissue have been barriers to ongoing research efforts.
With that said, stem cells from umbilical cord blood and adult adipose (fat) or bone marrow can also be coaxed to display many protein markers similar to those found in nervous system cells. It’s unclear whether these cells will ultimately be able to give rise to functioning neurons, but researchers continue to make progress.
Ultimately, there is much left to discover when it comes to the potential role of being able to regrow brain tissue and regenerative therapies such as stem cells in neurodegenerative conditions and brain injury. What we’ve already seen is promising, however. As experts continue to develop a deeper understanding of how stem cells and neurons can work together, patients with these challenging conditions will likely continue to benefit from evolving treatment options. If you would like to learn more then contact a care coordinator today!
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.
Oligodendrocytes are key neural cells responsible for producing myelin sheaths that wrap around neuronal axons in the central nervous system[1]. Considering that thymosin β4’s (Tβ4) ability to promote neurological recovery in a range of neurological diseases has been well established, Chopp & Zhang (2015) propose oligodendrogenesis as the common link by which Tβ4 supports and promotes recovery after neural injury and neurodegenerative disease.
Citing Tβ4’s propensity to alter cellular expression and target multiple molecular pathways involved in neurovascular remodeling and oligodendrogenesis, it warrants further study into Tβ4 as a restorative/regenerative therapy for neurological injury and neurodegenerative diseases.
Traditional treatment of neurological diseases, including stroke, traumatic brain injury (TBI), and multiple sclerosis have typically focused on the reduction of lesions and produced no effective or beneficial long-term therapeutic outcomes. As a result, new proposals suggest renewed focus on therapeutic efforts designed to facilitate the restorative process present after injury and with specific focus on the enhancement of neurovascular recovery resulting in improved neurological recovery.
Among the many benefits of using Tβ4 in the restorative/regenerative therapeutic process is that, unlike neuroprotection treatments that must be introduced to damaged tissue before irreversible damage occurs, this treatment can be administered several days – even weeks – after injury and still stimulate the naturally-occurring regenerative process that has been demonstrated to be beneficial in treating several conditions, including stroke and TBI.
Specifically, Tβ4 promotes the remodeling and restoration of the CNS/PNS post-injury and has been shown to improve neurological recovery by allowing for improved neurovascular plasticity, neurite outgrowth, myelination of axons, as well as increasing the production and release of trophic factors to further support the remodeling of the nervous system.
Multiple animal models have demonstrated that Tβ4 facilitates the restorative neurological process by simulating oligodendrocytes (OLGs) and specifically OLG progenitor cells (OPCs) in the CNS. It appears that Tβ4 expedited multiple pathways of neurological recovery by stimulating tiny non-coding RNAs known as microRNAs to promote the generation, translation, and differential of OPCs and OLGs.
While these findings are promising, what remains yet unknown is specifically how Tβ4 affects, or perhaps more appropriately, influences, microRNAs to communicate specific neurological restorative and regenerative instructions among various cells. The predominant theory emerging from relevant research is that this process of intercellular communication is created and moderated by tiny lipid particles known as exosomes.
Considering the safety of Tβ4 for use in human trials and the potential for Tβ4 to treat neurological injury and degeneration, future clinical trials focusing on Tβ4’s specific influence on exosomes, and as a therapeutic restorative for neurological treatment and regeneration, is thought to hold promising clinical translation for future treatments of neurological disease and injury.
Neurodegenerative diseases affect millions of people across the globe. Parkinson’s disease (PD) and Alzheimer’s disease are the two most common illnesses within this category, and as of 2016, more than five million Americans were living with Alzheimer’s disease alone. It’s estimated that the prevalence of neurodegenerative diseases will only increase in the coming years with the aging population.
Characterized by the loss of function and death of nerve cells, neurodegenerative diseases cannot currently be cured. There are medications available to control symptoms, but patients don’t always respond to these drugs as desired. Moreover, there are often side effects which can further diminish patients’ health and wellbeing.
Stem Cells for Neurodegenerative Diseases
As a promising alternative to traditional medicine, stem cell therapy is being explored as a treatment for neurodegenerative conditions. These remarkable cells act as the basis from which every other differentiated cell type in the body is created. They can self-renew and transform into nearly any cell type. With these capabilities, researchers are finding that stem cells can repair damaged neurons, thus controlling the rate of disease. In some cases, it’s possible that stem cells could even reverse some of the damage already done.
There are several different types of stem cells being investigated for neurodegenerative conditions, including:
Tissue-specific stem cells: These stem cells can give rise to multiple organ-specific cells and are typically located in areas of the body that can self-renew, including the skin and blood.
Mesenchymal Stem Cells (MSCs): MSCs are located within the bone marrow and can differentiate into several types of cells, including cartilage, bone, and muscle. They have strong self-renewing properties and are therefore an ideal candidate for tissue repair.
Induced Pluripotent Stem Cells (iPSCs): iPSCs are artificially derived from adult cells and programmed back to pluripotency. This creates an unlimited source of any cell type. Although iPSCs have been used in developing medications and disease modeling, further research is needed to determine their efficacy in other types of treatment.
Neural Stem Cells (NSCs): NSCs are derived from specific areas of the brain and are thus considered specialized cells. Like other stem cells, they are self-renewing and multipotent.
Stem Cells for Neurodegenerative Diseases
The research into how stem cells can help patients with neurodegenerative diseases is ongoing. With that being said, tremendous progress has already been made. In specific, stem cell therapy is being used to help treat the following conditions:
Alzheimer’s Disease: Columbia University researchers have discovered a groundbreaking process through which skin cells could be converted into brain cells. With further research, this process could help to create neurons which have been compromised by conditions such as Alzheimer’s disease.
Parkinson’s Disease: PD patients experience a decline of dopamine as brain cells are destroyed. As dopamine levels drop, patients experience a range of challenging symptoms, including issues with movement and cognition. Recently, stem-cell derived dopaminergic neurons created through ESCs and iPSCs have emerged as a potential option for replacing compromised brain cells.
ALS: ALS has puzzled researchers for decades, largely due to the inability to source motor neurons in large enough numbers for studying. Recently, however, Harvard researchers have acquired mature cells that can be manipulated back into stem cells from ALS patients, which could lay the foundation for studying new therapies. Contact a Care Coordinator today for a free assessment!
As the name suggests, neurodegenerative diseases are a disease of the nervous system in which nerve cells (i.e. neurons) become dysfunctional and die. As more nerve cells die, certain brain functions slow, change or stop. Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and Amyotrophic lateral sclerosis (ALS) are examples of debilitating and even fatal neurodegenerative diseases. There are no cures for these diseases, but symptom management is the primary focus for patients seeking treatment options.
Neurodegenerative diseases are an attractive target for regenerative medicine. The approach makes sense intuitively; if brain cells are inflamed, dysfunctional, and dying, can mesenchymal stem cells be applied as a targeted approach so that they may differentiate into new brain cells and release all the helpful substances stem cells are known to release. Many researchers share this optimism and believe in the promise of stem cells as a treatment for neurodegenerative diseases. Indeed, Drs. Joyce and coauthors discuss what steps have already been taken to develop stem cells into a potential treatment for neurodegenerative diseases.
The authors describe scientific studies that show how mesenchymal stem cells “promote endogenous neuronal growth, decrease apoptosis and regulate inflammation.” In other words, stem cell transplantation supports nerve cell growth, decreases cell death, and reduces the damaging inflammation that is seen in some neurodegenerative diseases like multiple sclerosis.
According to the scientists, stem cells “can mediate modification of the damaged tissue microenvironment to enhance endogenous neural regeneration and protection.” This means that stem cells can make the area around the diseased brain more favorable to nerve cell growth and development. Stem cells create a protective environment for nerve cells to live and operate.
Clinical trials that study the effects of stem cells in neurodegenerative diseases are progressing. Some studies show that stem cells might be able to slow the rate at which muscle strength declines and are considered safe for those with ALS. Likewise, patients with Huntington’s disease showed motor and cognitive improvements two years after receiving a stem cell transplant into the damaged region of their brains. Moreover, stem cells transplanted into patients with Parkinson’s disease were found to be alive and well 10 years after transplantation. Perhaps more importantly for patients, stem cells provided relief of Parkinson’s disease symptoms.
As of now, stem cell treatments for neurodegenerative diseases can be directed to the targeted tissues with administration techniques such as intranasal or intrathecal injections to bypass the blood-brain barrier. While these injections have been shown time and again to be safe, patients and their providers must consider the process and their safety. Continued research is ongoing and those seeking an alternative option should do their research and discover how regenerative medicine may potentially help them manage their symptoms.
Reference: Joyce, N., et al. (2010). Mesenchymal stem cells for the treatment of neurodegenerative disease. Regenerative Medicine. 2010. Nov; 5(6): 933-946.
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