Stem Cells: Therapy, Controversy, and Research

Abstract

Stem cells are literally the gods of all cells. They have the potential to develop into so many different types of cells within the body. For many untreatable neurodegenerative disorders, stem cell research offers great promise and hope for a cure to these progressive diseases. Here we discuss what a stem cell is and the basic functions, how it can be used to help alleviate one of the largest symptoms of Alzheimer's disease, and research of stem cells on neurological disorders and how stem cell development correlating with Alzheimer's can create new experiments for clinical research. The human brain is prone to neurodegeneration and is unable to counteract the neuronal loss by regenerating lost cells. Patients with neurodegenerative conditions progressively lose neurons yet have an absence in the appropriate plasticity response that would replace the lost ones (Tincer, Mashkaryan, Bhattarai & Kizil, 2016). Regeneration or neuroreplacement in neurodegenerative diseases may seem like an unattainable goal, however, when you look at model organisms, they may hold potential for advancement in cellular therapies and replacement treatments.

Intro: What is a Stem Cell?

Stem cell are cells with the potential to develop into many different types of cells in the body. They are a repair system and are different from other cells in the body in a few different ways. The main being that stem cells can divide and renew themselves over a long period of time and are unspecialized; because of this stem cells have the potential to become specialized cells that go on to perform specific functions within the body. Stem cells which divided under the right conditions go on to form more and more daughter cells, some of which become more stem cells while others become specialized cells. Some examples of these specialized cells are heart cells, muscle cells, blood cells, and brain cells. In the past regular connective tissue has been taken by researchers and reprogram to become functional heart cells. In one study, animals with heart failure that were inoculated with new heart cells experienced enhanced heart function and an increase in their survival time (Mayo Clinic, 2018).

Stem cells are noted as being one of the body's raw materials (Mayo Clinic, 2018) meaning all other cells with a specialized function are generated from them. That being said, stem cells can literally transform into any specialized cell under the right conditions in the body or laboratory setting. Stem cells can be guided into becoming specific cells that can be used to regenerate and repair diseased or damaged tissue within the body (Mayo Clinic, 2018). For various untreatable neurodegenerative disorders, such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) (the current-approved drugs provide only symptomatic relief) (Bali, Lahiri, Banik, Nehru, & Anand, 2017), stem cell therapy gives potential to be used in the regrowth of new tissue systems for use in transplant and regenerative medicine.

Some Fun Summaries of Scholarly Papers

In an article published in 2012 by Jun Tang, it was discussed how close a stem cell cure really was to Alzheimer's disease. Alzheimer's disease (AD), Parkinson's disease and Huntington's disease occur as a result of the neurodegeneration process. There is no current proven cure for AD, drug therapy can only improve cognitive symptoms temporarily and no treatment options can stop, reverse or even slow down the rate that Alzheimer's affects the brain. Non-drug treatments such as behavioral interventions and gene therapy can only bring temporary symptomatic relief but still does not stop the progression of this disease. Neurogenesis has been proven to exist in restricted regions of the adult brain, this is supported by the identification of neural stem cells which suggests that the adult central nervous system may be open to cell intervention. A combination of psychosocial, behavioral, and pharmacologic strategies intends to slow the process of Alzheimer's and preserve the quality of life for as long as possible. A neuro-replacement strategy would undoubtedly become more viable as we develop our understanding of the pathogenesis of AD and aid in research aiming to clarify the physiological role of neural stem cells in the adult brain (Tang 2012).

In 2016, an article by Tincer, Mashkaryan, Mhattarai, and Kizil was published stating how neural stem/progenitor cells (NSPCs) can be used as a therapeutic approach to reverse or slow the loss of affected neurons. Stem cells could provide an environmental support to residing neurons by creating neurotrophic factors and creating additional neural networks in affected areas. In a healthy brain, the NSPCs are the multipotent stem cells that are capable of production, self-renewal, and generation of new neurons, astrocytes, and oligodendrocytes. Enhancing their production rate and variation size, combined with new methods aiming to increase the survival and integration of neurons into the brains circuitry may provide a regenerative contribution in a highly unfavorable neurodegenerative environment. It was discussed how zebrafish can be used as a model organism due to their extensive regenerative ability in the brain and this may address the molecular programs needed to counteracted neurodegeneration by enhanced neurogenesis. The programs in the zebrafish brain may show the difference between the neurogenic abilities of NSPCs and the regenerative capabilities of their brains in correspondence to mammalian brains. By studying the zebrafish brains there is an opportunity to understand how vertebrates could efficiently form neurons after neuron loss. Although the zebrafish brain does not reflect the exact same physiological and neurochemical complexity of the human brain, they do have highly conserved phylogenetic similarity to humans in brain structure, neuronal types and developmental terms (Tincer, Mashkaryan, Mhattarai, and Kizil, 2016).

New Application: Stem Cells and Alzheimer's

Alzheimer's disease (AD) is a progressive neurodegenerative illness and the most common form of dementia. AD is a progressive disease meaning that the dementia symptoms associated with it gradually worsen over time. In the early phases, memory loss is mild but as time goes on individuals lose the ability to converse with others and respond properly to their environmental stimuli. AD is the sixth leading cause of death in the United States. Those with this disease live maybe an average of eight years after their symptoms become noticeable to others but the survival range can go from four to twenty years depending on the individual's age, lifestyle, and other health conditions (Alzheimer's Association, n.d.).

Alzheimer's disease is characterized by two types of abnormal brain structures: amyloid-beta (A??) plaques and neurofibrillary tangles (Harvard, n.d.). A?? plaques are kind of like sticky clumps of protein bits that accumulate around and attack brain cells. These protein plaques in the brain could be created as our immune system fights off invading microbes but overall the function of the plaques still remains unclear (Ananthaswamy, 2016). Neurofibrillary tangles are twisted fibers of protein that build up inside the neurons of Alzheimer's patients. The memory loss and communication problems typical of AD don't normally appear until after age sixty because it takes time for these structures to accumulate (Harvard, n.d.).

There is not a current prevention method nor cure for Alzheimer's disease (Tang, 2012). There are some treatments for the symptoms, but these remedies cannot stop the progression of AD. That being said, one of the symptoms that could potentially be alleviated by the use of a neural stem cell transplant is an individual's memory. Memory is located in a few areas of the brain, but some of the primary areas would be the prefrontal cortex, temporal lobes, and the hippocampus. The prefrontal cortex plays a key role in the processing of short-term memory and retaining long-term memories. The temporal lobes process the semantics in both speech and vision including the processing of complex stimuli such as faces, and scenes aid in the formation and retention of long-term memory (Mastin, n.d.). The hippocampus plays a role in the formation of new memories and the detection of new surroundings, occurrences, and stimuli (Mandal, 2018). Basically, all memories have to go through the hippocampus in order to be sent to the location in the brain in which they'll be stored, many of the memories being sent to the temporal lobes and the prefrontal cortex.

By doing a cellular replacement procedure, there could be a potentially increase the neuroplasticity in the brain by creating new synapses in these specific areas of degeneration to help retain memories. Cellular replacement implicates the substitution of specific neuronal subtypes lost in disease and successive grafting into affected areas (Tincer, Mashkaryan, Bhattarai & Kizil, 2016). To state the procedure in lament terms, one would go into the brain of the patient and take biopsies of diseased cells from the prefrontal cortex, temporal lobes, and hippocampus. Once taken out, the original neural cells taken from the brain would be disregarded and traded out for embryonic stem cells. The embryonic stem cells would be modified with a basic protocol for the directed differentiation and selected precursors in order to turn them into the neural cells we are looking to replicate before transplantation into the brain. The newly transplanted cells should integrate and recapitulate a neural network similar to that of a healthy brain.

Replenishing these areas with new regenerated cells to help prolong memory of the individual, the potential increase in the end quality of life would be incalculable. By increasing the amount of time of AD patients have with some sort of improved memory retention there is no telling what the benefits could be. One of the worst factors of caring for a person diagnosed with Alzheimer's is seeing them forget their loved ones and their very familiar surroundings. If cellular replacement could increase the neuroplasticity of these three primary memory locations, it may be easier on the caretakers and patients who are affected by Alzheimer's due to the potential retention of core memories such as where the individual lives, basic hygiene and daily routine, and remembering faces of their close family and friends. Although this would not be stopping the progression of the degeneration on the whole brain, by trying to salvage these parts the potential end quality of life would skyrocket.

Conclusion

In theory, there is no limit to the number of neurodegenerative diseases that could be treated with stem cell research. These complex disorders have various cell types in which cellular therapies may just be the key to unlocking the cure or at least help in the alleviation of symptoms caused by them. Neurogenesis has been proven to exist in restricted regions of the adult brain which suggests that the adult central nervous system may be open to cell intervention. Neural cellular replacement requires new research and methods in order to work around the hurdles of reverting neuronal death, preventing synaptic degeneration, and encouraging the increase in plasticity of neural stem cells. Since humans lack the proper plasticity response, looking to model organisms might play a key role in finding genetic tools needed to decrease the rate of neurodegeneration in humans. Although most of these studies are performed in embryonic stages or stopped generating a progressing neurodegeneration model that could be addressed in adult stages.

Works Cited:

Alzheimer's Association. (n.d.). What Is Alzheimer's? Retrieved November 29, 2018, from https://www.alz.org/alzheimers-dementia/what-is-alzheimers

Ananthaswamy, A. (2016, May 25). Alzheimer's may be caused by brain's sticky defence against bugs. Retrieved November 29, 2018, from https://www.newscientist.com/article/2090221-alzheimers-may-be-caused-by-brains-sticky-defence-against-bugs/

Bali, P., Lahiri, D. K., Banik, A., Nehru, B., & Anand, A. (2017). Potential for Stem Cells Therapy in Alzheimer's Disease: Do Neurotrophic Factors Play Critical Role? Current Alzheimer Research,14(2), 208-220. doi:10.3897/bdj.4.e7720.figure2f

Harvard Stem Cell Institute. (n.d.). Alzheimer's Disease. Retrieved November 29, 2018, from https://hsci.harvard.edu/alzheimers-disease-0

Mandal, A. (2018, August 23). Hippocampus Functions. Retrieved November 30, 2018, from https://www.news-medical.net/health/Hippocampus-Functions.aspx

Mastin, L. (n.d.). Parts of the Brain. Retrieved November 29, 2018, from https://www.human-memory.net/brain_parts.html

Mayo Clinic Staff. (2018, October 24). Stem cells: What they are and what they do. Retrieved November 29, 2018, from https://www.mayoclinic.org/tests-procedures/stem-cell-transplant/in-depth/stem-cells/ART-20048117?p=1

Tang, J. (2012). How close is the stem cell cure to the Alzheimer's disease. Neural Regeneration Research,7(1), 66-71. doi:10.3897/bdj.4.e7720.figure2f

Tincer, G., Mashkaryan, V., Bhattarai, P., & Kizil, C. (2016). Neural stem/progenitor cells in Alzheimer's disease. Yale Journal of Biology and Medicine,89(1), 23-35. doi:10.3897/bdj.4.e7720.figure2f

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