Use of Embryonic Stem Cells to Cure Disease

¶ … Embryonic Stem Cells to Cure Disease

Embryonic Stem Cell

Derivation of Human Embryonic Stem Cells

Generation of Cardiomyocytes from Human Embryonic Stem Cells

Purified Population of Cardiomyocytes

Use of Transgenes in Differentiated Cardiomyocytes

Use of Human Embryonic Stem Cells for Heart Conditions

Neurological Disorders and Use of Human Embryonic Stem Cells

Parkinson's Disease

Stroke

Huntington's disease

Amyotrophic Lateral Sclerosis

Human Embryonic Stem Cells for the Generation of Functional Hepatic Cells

Ethical Considerations of Using Human Embryonic Stem Cells

Social Oppression

Value of the Embryo

Pluripotent stem cell cultures were isolated in 1981 by Evans and Kaufman from mouse blastocysts. It was found that these cells were capable of self-renewal having a long-term capacity to remain undifferentiated in certain provided culture conditions. Studies have highlighted the basic difference between stem cells and embryonic stem cells. Embryonic stem cells have the potential to differentiate into three germ layers. These cells have an additional capacity to proliferate in culture conditions in an undifferentiated state plus these cells usually disappear after differentiating into germ layers. For clinical purposes, origin of human embryonic stem cell is pre-implantation embryo. The stem cell lines have been derived from inner cell mass of human blastocysts that are produced by in-vitro fertilization. The studies have shown that human embryonic stem cells have the properties of embryonic stem cells (Cai et al. 2007, p. 1229). The properties include derivation from pre-implantation embryo, prolonged proliferation in the culture in an undifferentiated state and a capacity to form three germ layers. In addition to this, it has been seen that human embryonic stem cells can maintain diploid karyotype and an expression of higher telomerase activity when cells are kept in cultures for longer periods.

There are two main properties of embryonic stem cells, indefinite cell renewal and an ability to differentiate into one or more cell types. Successful studies and applications of murine embryonic stem cell research have paved the way to study more about important applications of human embryonic stem cells. Several tissues in the human body depend on a pool of adult or somatic stem cells for maintenance. The tissues include hematopoietic system, skin, gut and some parts of the central nervous system. Studies have shown that the depletion of stem cell pools can lead to many diseases that include leukemia, lymphoma, and certain genetic defects. Other kinds of diseases involve tissue destruction where these tissues are unable to be revived by the stem cell pools. These diseases and conditions include Type 1 diabetes that occurs because of auto-immune destruction of pancreatic beta cells and liver failure occurring because of liver cirrhosis either because of toxins or certain infectious agents (Zou et al. 2009, p. 98). Main way to treat these diseases is replacement of stem cell pools in the body. Reports and studies have highlighted success of bone marrow transplants and direct organ transplants. Human embryonic stem cells can be triggered to differentiate into adult stem cells in order to replace the damaged stem cell pool in the body clinically in order to regenerate damaged or diseased tissues and organs (Lerou, and Daley, 2005, p. 321). Organ transplantation has been lesser appreciated as compared to replenishment of stem cells based on an immune barrier, where immune-suppression becomes necessary to prevent graft rejection (Gepstein, 2002, p. 869).

For proper clinical and medical usage of embryonic stem cells, it is important that developmental pathways of tissues within an embryo are studied and understood. Many kinds of embryonic stem cells have been characterized including insulin secreting cells, neural tissue, cardiomyocytes, endothelial cells, hematopoietic cells, hepatocytes and osteoblasts. Thereby stem cells can be used clinically in order to treat medical conditions in these tissues and cells (Lindvall, & Kokaia, 2006, p. 1095).

Derivation of Human Embryonic Stem Cells

It has been reported that cells in mammalian embryo have the capacity to regenerate into any tissue type in the body. This property is termed as pluripotency. After the occurrence of fertilization, at the stage of blastocyst, formation of hollow sphere of cells takes place that has an outer cell layer and an inner cell mass. The outer cellular layer develops into trophectoderm giving rise to placenta and other tissues. All the other tissues in the body are developed by the inner cell mass (Cai et al. 2007, p. 1231).

Generation of Cardiomyocytes from Human Embryonic Stem Cells

For clinical usage, many protocols have been used in order to trigger differentiation of human embryonic stem cells to specialized cardiomyocytes. Studies have shown that 5-aza-20-deoxycytodine has a great enhancing effect on differentiation of human embryonic stem cells towards cardiomyocytes (Mummery et al. 2002, p. 2734). However in these cases, the obtained cardiomyocytes are immature and have properties and functions related to fetal cardiomyocytes. Thereby there is a need that better protocols are developed that can help in the development and differentiation of human embryonic stem cells towards specialized cardiomyocytes rather than fetal or immature cardiomyocytes (Stojkovic et al. 2004, p. 260).

Purified Population of Cardiomyocytes

Second main fact highlighted in the studies is that in order to attain purified population of engrafted heart cells, it is important that protocols are followed that can generate purified population of heart cells. For clinical usage, purified cell population is used rather than mixed population for best results. For example, in certain clinical and medical conditions, it is important that only specific kinds of cardiomyocytes are used rather than the mixed populations. In the case of myocardial infarction and chronic heart failure, ventricular cardiomyocytes are needed, not sinus-nodal type because sinus-nodal type are more arrythmogenic and are reported to have caused morbidity in patients (Bhattacharya et al. 2004, p. 2959).

Use of Transgenes in Differentiated Cardiomyocytes

Human embryonic stem cells can generate differentiated heart cells when specific culture conditions are provided that can be used for clinical purposes that include heart failure and myocardial infarctions. In some cases, the previous studies have reported the usage of transgenes. Reports and studies have highlighted that transgenes can be a source of mutagenesis in the cells affecting the functions of cells in a negative way. The only advantage highlighted in the case of transgenic approach is that it can help in highlighting developmental pathways helping the scientists in learning about the lab culture conditions appropriate for the development of cardiomyocytes without any reliance on transgenes (Stojkovic et al. 2004, p. 263).

Use of Human Embryonic Stem Cells for Heart Conditions

In the western world, one of the main heart diseases being the main reason of mortality includes ischemic heart disease. Within the heart, irreversible cell damage is triggered based on oxygen deprivation and irreversible cell damage can cause heart cell death. The damaged cells are thereby in a need to be replaced by newer cells provided by cardiomyocytes transplantation. One of the main advantages in these cases is that permanent damage can be slowed down as newer cells can replace newer ones (Cai et al. 2007, p. 1232).

Neurological Disorders and Use of Human Embryonic Stem Cells

Some of the most common neurological disorders include multiple sclerosis, Parkinson's disease, and stroke. These diseases and conditions are caused by the loss of neurons and glial cells. In recent era, it is being hoped that a large and an inexhaustible source of neurons and glia will be provided by the stem cells in order to ensure success of therapies of the highlighted medical conditions to trigger cell replacement and neuroprotection. For this purpose, embryonic stem cells or fetal or adult stem cells from adult or fetal central nervous system are considered as best suitable. For clinical applications of these cells, it is important that specific kinds of cells and neuroprotective molecules are used (Gepstein, 2002, p. 866).

Parkinson's disease

Parkinson's disease is characterized by the gradual loss of nigrostriatal dopamine-containing neurons but in some cases it has been reported that there is a loss in non-dopaminergic neurons as well. Main symptoms of Parkinson's disease include lesser movement, rigidity, tremors, and an increased instability in postural movements. Some of the main therapies that are being used in the modern days include oral administration of L-Dopa along with dopamine receptor agonists (Lindvall and Kokaia, 2006, p. 1095). Another therapy includes the deep brain stimulation of the subthalamic nucleus. These treatments have been seen to be effective for some symptoms. There are some associated disadvantages in the case of these treatments and these include an inability to control the progression of the disease. Thereby there is a need to find an alternative that can help stop the progression of the disease and can cure the disease rather than treating some symptoms. Significant improvements in mobility and long lasting disease cure are what needs to be targeted by the help of stem cells (Bhattacharya et al. 2004, p. 2957).

Many clinical trials have been conducted where fetal dopaminergic neurons have been transplanted replacing the damaged dopaminergic neurons showing major and long lasting improvements in the patients. Thereby most promising results have been shown by embryonic stem cells having the capacity to regenerate into dopaminergic neurons. However. still a great deal of research and studies are needed in the order to study the efficiency of stem cells in innervation of the striatum, dopamine release, and relief from the symptoms of Parkinson's disease (Mummery et al. 2002, p. 2736).

Stroke

Strokes are caused by the blockage of cerebral artery causing focal ischaemia, loss of glial cells and neurons, along with cognitive and sensory impairments. There are no current therapies that can repair the damage caused by the stroke and even if some symptoms are relieved by the help of any minor therapy, it is considered helpful. Certain sources of the stem cells include fetal brain, teratocarcinoma or neuroepithelial cell lines, umbilical cord and bone marrow. These cells have shown great changes in the conditions caused by stroke. The studies have shown that these cells also secrete trophic factors that play important roles in cell survival, proper cellular functioning and regeneration. Thereby the cells can replace dead neurons, cause increased remyelination of the axons and repair damaged neuron circuits (Barberi et al. 2006, p. 0555).

Huntington's disease

Huntington's disease is a disorder that has been termed as fatal and is characterized by chorea, or excessive spontaneous movements as well as progressive dementia. This disorder is caused by the death of projection neurons present in the striatum. When human embryonic stem cells are used clinically for the treatment of this disorder, the main focus is on the replacement of striatal neurons. But this therapeutical approach has been regarded insufficient and inefficient as in the case of Huntington's disease, the reports have highlighted progressive neocortical degeneration. Functional recovery in the patients is promoted by replacement of cells with grafts of fetal striatal neurons (Kehat et al. 2001, p. 412).

Amyotrophic Lateral Sclerosis

This disorder is more characterized by a dysfunction and an increased degeneration of the motor neurons at multiple locations including spinal cord, cerebral cortex as well as the brain stem. This disorder is characterized by a great progression in muscle weakness and death occurs in a few years. Thereby if human embryonic stem cells are used for therapy, it is important that stem cells must replace upper as well as lower motor neurons. In this case, it is also important that the new neurons generated by the stem cells must have the ability to integrate into neuronal circuitries. Various studies have studied the possibility of generation of lower motor neurons by using stem cells having the ability to develop functional synapse with the muscle fibers and cause an extension of the axons to ventral roots after a successful transplantation (Cai et al. 2007, p. 1237). This is a long-term approach.

An approach contrary to this approach is a short-term approach which focuses on the prevention of motor neurons from dying. Studies conducted on rats have shown that when human embryonic germ cells were delivered into the cerebrospinal fluid of the rats, motor recovery was seen based on the fact that cells migrated into the spinal cord. The studies have further highlighted that the efficiency of this process can be further improved by genetically modifying the stem cells in such a way that they can secrete molecules that can promote neuron survival (Kehat et al. 2001, p. 407).

Human Embryonic Stem Cells for the Generation of Functional Hepatic Cells

End stage liver diseases have been treated using orthotopic liver transplantation. A successful alterative to orthotopic liver transplantation is hepatocyte transplantation. Hepatocyte transplantation is an important alternative to whole organ transplantation in case of acute liver failure. This process can also help in decreasing the mortality rates. One of the major limitations in this case is the availability of human hepatocytes (Lerou, and Daley, 2005, p. 324). The main source of human hepatocytes is human embryonic stem cells. It has been reported that human embryonic stem cells can proliferate infinitely while maintaining the potential to differentiate into almost any kind of cell. Thereby if proper conditions are provided to the stem cells, these cells can be made to differentiate into hepatic cells. Second main advantage of generating hepatocytes from stem cells is that these cells can be used for drug testing as liver is an important detoxifying organ.

Studies have shown that the differentiation capacity of human embryonic stem cells into hepatocytes is lower; by this means there is a need to develop methods that can ensure progressive development of stem cells into hepatocytes. Studies have been conducted in which human embryonic stem cells have been induced with Activin A and FGF4 (fibroblast growth factor)/BMP2 (bone morphogenetic protein). An important role of Activin A was to induce and increase the endoderm differentiation of embryonic stem cells. On the other hand, hepatic differentiation was induced by the help of FGF4 (fibroblast growth factor)/BMP2 (bone morphogenetic protein) from the endoderm of stem cells. Thereby these cell lines can be promising for future drug testing and hepatocyte replacement in acute liver failure conditions (Stojkovic et al. 2004, p. 264).

Ethical Considerations of Using Human Embryonic Stem Cells

Biomedicine industry of the modern days has been characterized by the culturing and isolation of the human embryonic stem cells. These cells have been used for the benefit of mankind. By the help of these cells, many dying and diseased cells can be replaced resulting in the cure of a certain medical condition. One of the main characteristics of these cells is that they have the ability to renew themselves into any kind of cells and tissues depending upon the conditions provided.

It is immensely ironic that the technology that is being used for the betterment of life of the mankind faces an important question of the importance and the value of life. An important fact that needs to be highlighted here is that when embryos are used to harvest embryonic stem cells, it leads to the destruction of the embryos. Destruction of human embryos means the destruction of the beginnings of the human life. Thereby an important question of an importance of life emerges here. Should a life that has just begun be used to make improvements in the life that already exists? (Lerou, and Daley, 2005, p. 327).

Main ethical issues in relation to using human embryos as a source of stem cells have been highlighted in the Research Involving Embryos Bill 2002 and Prohibition of Human Cloning Bill 2002. Main focus of these bills has been on the destruction of human embryos to obtain stem cells and on the creation of human embryos in the case of cloning.