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Stem Cell Research Has Become Very Popular Biology Essay

Stem Cells are undifferentiated cells that have the capability of dividing for long periods of time. There are three basic types of stem cells, including: Embryonic Stem Cells, Adult Stem Cells and Induced Pluripotent Stem Cells. Embryonic stem cells are found in the embryo, fetus or umbilical cord and are pluripotent, meaning that they can develop into almost any of the 220 types of differentiated cells in the human body. These stem cells can be harvested through two ways:

→ In Vitro Fertilization: A fertilization process that requires a male's sperm cells and a female's egg cells to be fertilized in a culture dish, which develop into embryos that are then implanted in the female's uterus. In this process, more embryos are made than used and so, they are frozen and the male and female may decide to donate them to research.

→ Therapeutic Cloning: A process in which a patients cell is merged with a donated egg that had the donors nucleus removed and replaced with a nucleus from a patients cell. The egg is then stimulated by chemicals or electricity to produce an embryo with all of the patients genetic information.

An embryo contains around a total of eight cells and all of the stem cells it contains are totipotent; able to develop into any type of differentiated cell under the correct stimuli. When the embryo is three to five days old, it becomes a ball of around a hundred cells, called a blastocyst, that contains pluripotent stem cells. In order to develop a larger group of these stem cells or a stem cell line, scientist will remove the stem cells from the blastocyst and culture them. The stem cell line is established when the cells divide over a period of several months without differentiating. They are then frozen and stored.

Adult stem cells are found in amidst differentiated cells in various tissues and organs. The surrounding cells stimulate the stem cells to produce more of those cells as needed to replace and repair the surrounding differentiated cells. Since these cells can only form certain types of stem cells, it is considered multipotent. Examples include:

→ Hemopoietic Stem Cells: Adult stem cells found in red bone marrow that are capable of developing the many types blood cells, such as leukocytes, lymphocytes, platelets and red blood cells. Only a small amount of these stem cells are active under normal conditions, but if scenarios arise where blood cell restoration is needed, stem cells that were previously dormant will become active to regenerate the blood cells. The majority of this type of stem cells reside in the bone marrow of the bones of the pelvis and are harvested via a large needle inserted through the skin while the patient is under general anesthesia. The liquid marrow is then filtered and stored.

→ Stromal or Mesenchymal stem cells: Adult stem cells found in various tissues such as teeth, skin, skeletal muscles and the brain. These stem cells can differentiate into cells that make up bone, cartilage, fat and connective tissue.

→ Peripheral Blood Stem Cells: matured stem cells that have left the bone marrow and entered the blood stream. It is harvested from the donor after they receive growth factors, which increase the growth and maturity rate of the stem cells to ensure there is enough found in the blood, whereas without the treatment, there would be very few. They are harvested intravenously, where they are sent to a machine that separates the blood from the stem cells before the blood is returned to the donor.

→ Umbilical cord blood can also be stored as a source of stem cells, but the stem cells are only multipotent and can only develop into a limited number of differentiated cells.

There are a limited number of stem cells found in the body with a majority being found in the bone marrow and more specifically, in the pelvis. Closely resembling their surroundings, scientist must isolate them from differentiated cells by binding a fluorescent molecule with a protein commonly found on the surface of the stem cell causing them to "light up". Similarly to embryonic stem cells, stem cells in order to create stem cell lines.

• Essentially, induced pluripotent cells are "reprogramed" specialized cells. These specialized cells were altered to return to a stem cell like state.

• These stem cells would not require the destruction of an embryo for harvesting, therefore avoiding any ethical or political circumstances arising.

• This new approached to stem cells is still experimental as there are many things that are not known about them yet.

• induced pluripotent cells shared similar structures, expressed the same genes and grew the same way. In addition to these factors, the researchers were able to develop stem cell lines.

DNA

DNA, deoxyribonucleic acid, contains the genetic instructions for the composition of human beings. This self-replicating key to the existence of humans is composed of four chemical bases: Adenine, Guanine, Cytosine and Guanine. The sequence in which these base chemicals are arranged is referred to as the genetic code. In pairs, these base chemicals are attached to sugar and phosphate molecules; this grouping is called a nucleotide. Forming the shape of a double helix, the nucleotides become two long spiraled strands. The collective amount of DNA in the cell is what makes up the human genome.

Genes

Genes are made up of DNA and carry its instructions to form proteins. Chromosomes are a result of these genes being continuously coiled and so, each pair of chromosomes contain two copies of each gene with one being inherited from each parent. Each cell only expresses a certain amount of these genes, while others are repressed. This is where the phrase "turning genes on and off" comes from. If the genes contain certain formations of the genetic code, it can result in mutations such as cancer.

Proteins

Proteins are made up of a possible combination of twenty different kinds of amino acids that are determined by the cell's DNA. The genes develop the proteins through the transfer of the genes' DNA to a certain molecule, RNA (ribonucleic acid), which then directs it into the cytoplasm. This type of RNA, called messenger RNA, then brings the genetic information to an organelle called a ribosome where another type of RNA, Transfer RNA, assembles the protein out of amino acids. There are many different types of proteins and they can be categorized by function: Antibody (bind to certain particles to defend body), Enzyme (implement chemical reactions in cells and helps make new particles), Messenger: (send out signals to organize the function of cells), Structural component (support the cell), Transport/storage:(bind with atoms and molecules to move them). These molecules are needed in order for the body to achieve structure, function and regulation.

cells) Antigen System. These antigens make up a person's tissue type. Everyone has many pairs of these antigens, which were inherited from their parents-similar to chromosomes. Doctors try to achieve a match of six or more pairs and this is why a direct sibling would have the best chance of having a match.

→ Advantages: The donor's stem cells develops its own immune cells, which could potentially help to fight off any remaining cancer cells in an effect called Graft-Versus-Cancer Effect. If necessary, the donor could be asked to donate more stem cells or white blood cells.

→ Disadvantages: The donor's immune cells may attack the patient's cells as a foreign body; Graft-Versus-Host Disease. There is also a chance for rejection, in which the patient's cells attack the graft, but this is not as high of a risk because the patient's immune system is destroyed by chemotherapy and radiation in addition to being supressed by immunosuppressant drugs.

→ Umbilical cord blood is another source in which these stem cells can come from. Although, this method only works in children and small adults as there are a limited number of stem cells in the cord blood.

• Non-Myeloablative or Mini-Transplants

→ In patients who have other health conditions or the elderly, doctors' may choose to proceed with a modified allogeneic transplant.

→ This transplant allows for the patients to receive treatment, but with lower doses of chemo and radiation therapy.

→ Lower doses of radiation or chemo allow for the patient to keep some of their own stem cells, this means that the patient's cell count won't drop as low to help them have less of a risk of conditions worsening or developing.

→ In the Non-Myeloablative Transplant, the patient's remaining stem cell are in amongst the donor's stem cells.

→ In this process, the donor's stem cells will eventually replace all of the patient's stem cells and donor's cells would essentially give rise to a new immune response that could potentially fight the remaining cancer cells is another example of the graft-versus-cancer effect

→ This process will take place over many months.

→ Advantage: Helps in the treatment of cancer for patients that have underlying conditions that would worsen or potentially become fatal if they were to fully undergo engraftment

→ Disadvantage: There is a high chance that the cancer may reoccur and there is still the potential for Graft-Versus-Host Disease. As well, advanced staged cancers may not have as great of chance of success as lower staged cancers. The long-term outcomes for this treatment are still under experimentation.

Each patient that undergoes a stem cell transplant has a specially developed plan by their doctors, selecting the best treatment choices for their individual situations. The doctors may base their decision based on the type of cancer the patient has, its progression and staging as well as any other factors that may affect the outcome of the patient to ensure they receive the best and most effective treatment.

Complications

• Infection

→ Since it takes many months for the patient's white blood cell count to return to normal levels, infections are more likely to develop.

→ The low white blood cell count also means that even the smallest of infections can become life-threatening as there are a very limited amount of immune cells to help ward off infection.

→ Patients are given antibiotics and have routine checkups to ensure they are in otherwise good health.

• Bleeding

→ For a few weeks, patients will have a low platelet count and will run the risk of severe bleeding

→ There is great importance in place for injuries to be avoided.

• Graft-Versus-Host Disease

→ Occurs in allogeneic transplants

→ Donor immune cells attacks the patient's cells as the patient is seen as a foreign body

→ High risk organs that could be attacked include: the skin, the gastro-intestinal tract and the liver.

→ Can be acute, lasting around 25 days 10 to 70 days after the transplant, or chronic, lasting for an extended period of time 70 to 400 days after the transplant.

• Graft Failure

→ Also called rejection

→ The stem cells do not multiply in the bone marrow and as a result, the blood cell levels remain low.

→ Graft failure may be treated by a second dose of stem cells.

• Secondary Cancer

After receiving chemotherapy and radiation therapy as well as the stem cell transplant, some patients may experience a second tumour growing in a separate area of the body along with a possibility of the cancer they were treated for relapsing.

Although unproven, a very logical and promising topic has been of interest: the possibility of cancer itself having its own stem cells. It is believed by many scientist that cancer has a small group of pluripotent cells that possess the ability to self-renew. Cancer Stem Cells were first identified in leukemia by a group of Canadian Scientist at the University of Toronto led by Dr. John Dick in 1994. Three years later, they isolated the cancer stem cells and injected them into mice, which resulted in the mice developing leukemia. In 2007, they inserted one cancerous gene into a human stem cell and implanted it in mice. This allowed for researchers to observe how the human form of leukemia develops and how a cancer stem cell can give rise to a variety of different cells.

Scientists believe that these cancer stem cells are what create the cells of tumours and cause the development of abnormal cells. Therefore, the existence of these cells would explain how cancer may reoccur after traditional means of cancer therapy because if just a few cancer stem cells were able to survive, they would be able to regenerate the destroyed cancer cells. The cancer stem cells are hypothesized to create a duplicate, unspecialized copy of the cancer stem cell and a daughter cell that differentiates into the cells a tumour is composed of in each division. Also, cancer often goes into remission for an amount of time, but is able to relapse. So, this situation could be caused by the cancer stem cells becoming dormant, just as many normal stem cells react when they are not required, until there is some form of stimuli that causes them to become active again.

In order to study these cells, scientist must isolate these cells in order to identify and determine how cancer genes, or oncogenes, are expressed and to identify abnormalities that these cells possess. In addition, the knowledge of the expression of oncogenes could allow for the discovery of tumour-suppressant genes and treatment that will counteract the abnormalities.

By observing the abnormalities in the cancer stem cells, researchers can then compare its qualities to those of healthy stem cells to configure just how these cells function.

Currently, Researchers are trying to establish proteins found on the surface of these stem cells that trigger their behaviour, or gene expression, in order to determine how to change their genetics to stop them from dividing. Other researchers are working on interfering with the signal to grow from the environment around the stem cells, their niche, to stop them from multiplying in a cancerous matter.

Drug Development

Stem cells give scientists the ability to better understand how cancer works by observing the genes that they are composed of and compare them to the genes and cells that allow cancer to form and thrive. This would enable them to comprehend what genes they need to stop from sending out signals to create cancer cells and the cells that need to be destroyed in order to stop the formation or development of cancer. The stem cells can be isolated in order to study how they behave in certain environments or on their own, so that scientist may be able to decipher exactly how they work and their genetic composition. In addition, stem cells allow for new drugs to be tested on them to observe their safety or a specific patients cells in order to understand how they will react in a patient specific scenario. This could potentially result in shorter times for new drugs to be available for use on humans. Stem cells are a very controversial area of research. The main reason of this being that in order to harvest embryonic stem cells, one of the most promising types, it require the destruction of the embryo. The topic then becomes part of the larger ethical debate of the point in which a group of cells is considered a human, which has caused religious and political uproar.

In fact, the United States has a law, the Dickey-Wicker Amendment, which prohibits the use of tax dollars toward the creation of human embryos. This poses as a problem to many American researchers as federal funding is a major contribution to their efforts. Fortunately, this law did not affect any of the stem cell lines in existing and research was able to continue on them.

In Canada, there are guidelines that were implemented in 2007 by The Canadian Institutes of Health Research regarding the use of stem cells in research. The guidelines state many rules, including: the donors of the sperm and egg must be aware of the donation, it is prohibited to sell or receive funds from embryo donation, there is no non-human cells combined with the human embryo and research is only allowed within fourteen days of the formation of the embryo.

The controversy of embryonic stem cells is a topic that will continue to cause problems for researchers because it deals with a fragile topic that will never have an opinion that is one hundred percent "correct". This could cause hardships for researchers in the way of funding and obtaining the embryos to conduct their research. Potentially, this debate could slow the research and advancement of stem cell therapy due to political problems that could arise. Fortunately, this also allows for funding and focus in different areas of research that don't require the use of an embryo, such as the induced pluripotent stem cells. The potential for these cells could increasingly grow if any political problems occur because it would have the possibility to receive more funding. Also, the controversy provides stem cell research with a spot light that allows for a growing interest in the topic and a greater public knowledge of the positive possibilities of this research. Therefore, the controversy that surrounds the topic of embryonic stem cells could both help and hinder stem cell research.

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