Better treatment for neurodegenerative diseases

Embryonic stem cells provide better treatment for neurodegenerative diseases than adult stem cells. Discuss.

Neurodegenerative disease is a condition characterized by the loss of neurons and glial cells within the spinal cord and the brain, and accumulation of intracellular fibrillary inclusions. These specialized neuronal and glial cells have maintained numerous functions in different physiological activities ranging from movement through to memory. If disruptions occurred within the cells of the nervous system, it will not regenerate successfully, leading to irreversible changes and characteristic neurological disorder. Numerous diseases are distinguished as neurodegenerative diseases; examples include Alzheimer's disease (AD), Amytotrophic lateral scelerosis, Parkinson's disease (PD) and Huntington's disease (HD). Stem cells are characterized by the ability to renew themselves through mitotic division and differentiating into a diverse range of specialized cell types. Stem cells was first discovered by a Russian scientist in the early 20th century but was introduced into medical research in the 1960s by two Canadian scientists named Ernest A. McCulloch and James E.Till, who demonstrated the presence of self-renewing cells in mouse bone marrow. In recent years, many neurons and glia cells have been generated successfully from stem cells in a culture. Further researches have undertaken to prevent the death of neurons and the glial cells as well as the formation of these cells (Lindvall, 2006).

There are two types of stem: embryonic stem (ES) cells and adult stem cells, derived from either embryonic development stages or mature humans, respectively. Embryonic stem (ES) cells are derived from the inner mass of blastocyst, an early-stage embryo. They are pluripotent stem cells which mean that they are able to differentiate into various cells types. It is the pluripotency that distinguishes the ES cells from the adult stem cells. The ES cells have the ability to regenerate to all cell types in the body unlike the adult stem cell, which provide a limited number of cell types. This shows that the ES cells provide better advantage for research and regenerative medicine because of their potential of self renewal and plasticity. Adult stem cells are also known as somatic cells that multiply by cell division to replenish dying cells and regenerate damage tissues. In many researches, scientists find a great deal of interest using adult stem cells as they have the ability to divide or self-renew continuously and generate all the cell types of the organs from which they originated. Previous experiment indicated that adult stem cells have the potential to regenerate an entire organ from a few cells (Laurance, 2008). One previous experiment has been conducted in 2008, where a human trachea that has been grown from adult stem cells taken from the bone marrow from the patient was transplanted and was successful. (Laurance, 2008) Adult stem cells have been used for many years to successfully treat leukemia and related bone and bone cancer.

Medical researchers believe that stem cell therapy has the potential to dramatically change the treatment of human disease, specifically by replacing irreversibly disrupted cells. Stem cell treatment and technology are of eminent interest in research studies to treat diseases and there are high hopes for the implication of stem cells in the treatment of neurodegenerative diseases such as Parkinson's disease and Huntington's disease have used adult and ES cell treatment. In recent years, there has been a strong interest in using adult stem cells to treat neurodegenerative diseases. But, there have been many debates whether ES cells provide better treatment than adult stem cells. Studies of stem cells had a scientific breakthrough researchers successfully isolated a single cell from a 'teratocarcinoma', a form of cancer, that was able to replicated and grow in cell culture as a stem cell. The high success rate for using stem cell research in therapy is due to extensive plasticity and self renewal properties the stem cells obtained. The main discussion is whether embryonic or adult stem cells provided better treatment for neurodegenerative diseases.

Huntington's disease (HD) is an inherited, autosomal disease which is a fatal and incurable neurodegenerative disease. This particular characteristic is by excessive and spontaneous movements, this can be characterized by chorea and progressive dementia. (Lindvall, 2006). This disease is caused by a genetic mutation known as a trinucleotide repeat that increase the number of repeats in a particular gene called HTT gene. The HTT gene is located within a short arm of the chromosome 4. (Walker, 2007) This alteration leads to a number of repeats creating a chain of glutamine called polyglutamine tract or polyQ tract, consequently leading to the destruction of Acetylcholine (ACh)-secreting and ?-Aminobutyric acid (GABA)-secreting neurons in the basal ganglia (also called the striatum)and cerebral cortex of the brain. The neurological disruption cause symptoms of dementia or restriction of movements to progressively appear as the basal nuclei and frontal lobes slowly degenerate. (Watanabe) There is no cure for HD, but there are many treatments to reduce the severity of chorea, using exercise and cognitive therapy to reduce the symptoms. Such as tetrabenzaine, this was developed to reduce the severity of symptoms. There are many possible treatments that are currently being investigated, as scientists show greater interest in this particular neurological disease; specifically due to the fact that there is no cure. One research study focused on the use of embryonic stem (ES) cells. Using a fetal human brain tissue may provide a useful approach to reduce neuronal damage in the brain and recent data indicated there have been improvements in motor and cognition after fetal cell transplantation. (Kim, 2009) Using neural tissues, which compromise both neurons and glial cells, offer a new way to provide radical treatments of HD disease. Adult stem cells were taken into consideration to provide treatment for this disease. An experiment was conducted using a cell from the subventricular zone (SVZ) taken from an adult rat brain and grown. The tissue was then transplanted into a rat model that had HD symptoms and this method was proven to be a success. (Vazey, 2006)

Parkinson's disease (PD) was named after the English apothecary James Parkinson, who wrote a detailed description of the disease in "An essay on shaking palsy" (1817). This disorder is caused by a gradual loss of nigrostriatal dopamine-containing neurons or the degeneration of non-dopaminegic neurons. (Dunnett, 1997) The result is gradual, generalized increase in muscle tone and the appearance of symptoms characterized by PD. People who suffer from PD have difficulty starting voluntary movements because the muscle groups do not relax. There are current for PD sufferers. One of the treatments is taking L-dopa as oral medication and another treatment is deep-brain stimulation in the subthalamic nucleus. These treatments may have few improvements of symptoms but are associated with various side effects and do not stop the disease from progressing. (Lindvall, 2006) Scientists are interested in using stem cell therapies because it is clinically competitive. This new therapy must have long lasting results and improvement to the current treatments. There are currently clinical trials using ES cells to treat PD. By transplanting low doses of undifferentiated mouse ES cells into the rat striatum resulted in a production of ES cells to differentiated into a fetal dopamine (DA) neurons which gradually restored and sustained DA-mediated neurons. (Bjorklund) There have been several clinical studies using adult stem cells to treat PD. Studies shows that by using neural stem cells (NSCs), taken from an adult rat model and have the potential to generate neurons including dopaminergic neurons and have been transplanted back to the individual. This indicated that NSCs is autologous can be an ideal way treat PD. (Arrias-Carrion, 2009).

Looking at clinical studies and trials used on rat or mice models we can see the potential use of using embryonic and adult stem cells. Following many researches, one treatment for HD is to use NSCs which could replace neurons that have been lost. Instead of using ES cells, adult stem cells have similar fundamental principles to treat neurodegenerative diseases. An experiment conducted indicated that the time the cells were grafted, majority of the cells were immature but expressed the neural progenitor marker. But, after transplanting the cells it has differentiated in vitro and transformed to neurons indicating the graft has indeed survived. Hence, these NSCs have the ability to reduce other experiments, the best treatment is to reduce any impairments and increase functions in the animal model with HD symptoms (Dunnett). There may be some evidence to show that adult stem cells can develop into neurons or glial cells but these observations are rare and reports are limited on models. (Toda, 2002)

By following intensive studies, the best treatment is to use ES cell therapy for HD sufferers. The transplantations of the fetal human brain tissue are a very useful strategy to reduce the neuronal damage within a HD sufferer. In recent studies, documentation has been provided to show there have been improvements in the motor and cognitive performance in HD patients after the fetal cell transplantation. (Boucherie, 2008) The idea was to use stem cells to restore or preserve the brain function by replacing or protecting the striatal neurons and the results was successful. Thus, these methods are possible to provide treatment for individual who suffer from neurodegenerative diseases

In recent studies, scientist has shown that NSCs in the brain have the ability to treat PD. This shows that neural stem cells or progenitor (NSCs) can preserves enough germinal character to maintain neurogenesis. (Arrias-Carion, 2002) and can develop into neural or glial. Even to date, there has been only one autologous human NSCs transplanted taken place. (Qu, 2009) By adopting this practice we can see that this clinical treatment established, provide a successful approach in a true autologous transplantation for PD sufferers; which help to understand the differential efficiencies of different stem cells to treat PD. There is another clinical trial, the first to use cell transplantation in PD using adrenal autografts. This is a complex procedure where one adrenal medulla of the PD sufferer is removed for dissection of particular cells and then transplanted back into the brain, but more research is needed.

The best stem cell treatment for PD is ES cells rather than adult stem cells. The application to use adult stem cell transplantation in the central nervous system (CNS) has been limited with patients with PD. The transplantation of human fetal dopaminergic neurons has produced long-lasting improvements within a majority of PD sufferers. These cells with properties of dopaminergic neurons have been generated in vitro from ES cells taken from the fetal brain or bone marrow. (Arrias- Carrion) This shows that ES cells are efficient and evidence provided, shows it is an effective treatment.

Stem cell research is beneficial for regenerative medicine and to improve long-term treatment as current therapies or drugs are short-term treatments and cause side effects when treating a neurodegenerative disease. By definition, stem cells have the ability to self renew continuously and be able to differentiate into various cell types. This is one of the main reasons why scientists are interested in this field and to find the potential treatment or cure for neurodegenerative disease. One of the break-through is to apply stem cells to cure leukemia and other related bone or blood cancer by using bone marrow transplant. This is a huge success in medical history to abolish diseases and cancer.

The idea of replacing loss of or regenerating neurons and glial cells, provide a long successful treatment. However, more potential researches needed to be carried out on adult stem cells as there are not enough studies to show their true potential. This idea is an exciting new possibility but there are many controversies over the use of ES cells on why embryonic or fetal resources should be used to generate stem cells if stem cells could be taken from an adult tissue. (KIM, 2007) Many individuals argued that using stem cells is immoral and unnatural and there have been several debated on the ethical implications of using ES cells. The uses of adult stem cells do not require destroying an embryo or generate. This can be argued that embryonic or fetal stem cells are more diverse in differentiating into various cell types. As well as providing a better, renewable and sufficient number of cell resources in cell-based therapy for individuals who suffer from neurodegenerative disorder. (Copray, 2003)

The ethical issues behind using ES cells always limit the widespread application and resources in using human clinical trials. The ultimate goal is to use stem cell research to human trial. Since, this is limited; there have been alternative methods to provide new treatments for other cell therapeutic application (Boucherie,2008) such as xenografts. A xenograft is either a transplantation of a cells, tissue or organs from one species to another. An example is from pigs to humans. Another alternative methods to provide new treatments are stem cells and other genetically manipulated or immortalized cell using animal models differ from human models and that the level of techniques may differ and the difficultly in knowing if it is successful in humans.(Boucheries, 2008). The next step is to use human models and no longer use animal models. However, this is a slow and steady process.

Another issue is providing a long term treatment for neurodegenerative diseases. There are still many obstacles for patients to adapt, such as the uncertainty of different stem cells will be the ideal source and if stem cell transplantation can increase the chance of recovery to the full potential. (Kim, 2002) Another interest to use adult and ES cells is previous experiments and research shows that overall stem cells maintain fundamental properties and plasticity to adapt to any environment given. This is a wide prospect to enhance technology and to improve medicine. (Dunnett, 2006)

The discovery of stem cells has challenged many scientists to become interested in neurodegenerative disease. Studies shows that embryonic stem cells provide better, long-lasting treatment for neurodegenerative diseases than adult stem cells because it is more versatile and the ability to renew and still remains one of the most effective source for clinical transplantation at this field.

References

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