Stem Cells

| April 8, 2015

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Assignment:

Using the five steps presented in slide 17 of the “Stem Cell Research Presentation”, design a proposal for a stem cell research project. The slides that follow slide 17 explain stem cell therapy in more detail. Use those slides to help you formulate your idea.

Step 1: Choose a disorder other than Parkinson’s disease, describe the disorder, and choose a problem associated with the disorder you will attempt to correct with the Stem Cell therapy.
Step 2: Choose the stem cell type you plan to use, and explain why you think your choice is the best choice for this disorder.
Step 3: Discuss the concept of why stem cells must be a close genetic match to the recipients.
Step 4: Describe how you will get the chosen stem cells into the patient.
Step 5: Following the procedure, what would you do to assist or monitor the treatment.

Stem Cells What are stem cells? • A stem cell is a cell whose job in the body is not yet determined. • Every single cell in the body “stems” from this type of cell. • Stem cells wait for a signal to tell them what to become. They have a lot of potential; they can become many different types of cells. Until they receive the signal, they must wait patiently and divide slowly. • When the stem cell receives the signal, it begins to differentiate, or gradually change into it’s destined cell type. – The signal tells it to turn on certain genes and make new proteins. This will help it look and act like the cell type that it is supposed to become. – Cells can be strikingly different. The differentiation process helps cells specialize so they can do their different jobs. – By the time it finishes differentiating, it will have stopped dividing too. The Goal of Stem Cell Research • Stem cells form the basic building materials for the human body, which makes them good candidates for restoring tissues that have been damaged by injury or disease. • For decades, researchers have been studying the biology of stem cells to figure out how development works, and to find new ways of treating health problems. How would stem cell therapy work? • The goal of any stem cell therapy is to repair a damaged tissue that can’t heal itself. – This might be accomplished by transplanting the stem cells into the damaged area and directing them to grow new, healthy tissue. – It may also be possible to coax stem cells already in the body to work overtime to produce new tissue. – To date, researchers have found more success with the first method, stem cell transplants. Different Kinds of Stem Cells • Early embryonic stem cells – The first step in human development occurs when a newly fertilized egg, or zygote, begins to divide, producing a group of stem cells called an embryo. – These early stem cells are totipotent, meaning they can become any kind of cell in the body. • Blastocyst embryonic stem cells – Seven days after fertilization, the embryo forms a hollow ball-like structure called a blastocyst. Embryos in this stage contain two types of cells. • Embryonic stem cells form the inner cell mass, which ultimately develops into the fetus. • Trophoblast cells make up the outside of the ball, and eventually become the placenta. – Embryonic stem cells in the blastocyst are pluripotent, meaning they can become almost any kind of cell in the body. • Fetal stem cells – After the eighth week of development, the embryo is referred to as a fetus. At this time, it has developed human like form. – Stem cells in the fetus are responsible for the initial development of all tissues before birth. – Like blastocyst embryonic stem cells, fetal stem cells are pluripotent, meaning they can become almost any kind of cell in the body. • Adult stem cells – “Adult” stems cells have a misleading name because infants and children also have them. – These stem cells reside in already-developed tissues, directing their growth and maintenance throughout life. – Adult stem cells are multipotent, meaning they can only differentiate into a limited number of cell types. Adult Stem Cell Transplant: Bone Marrow Stem Cells • Perhaps the best-known stem cell therapy to date is the bone marrow transplant, which is used to treat leukemia and other types of cancer, as well as various blood disorders. – Leukemia is a cancer of white blood cells, or leukocytes. Like other blood cells, leukocytes are made in the bone marrow through a process that begins with multipotent adult stem cells. Mature leukocytes are released into the bloodstream, where they work to fight off infections in our bodies. – Leukemia results when leukocytes begin to grow and function abnormally, becoming cancerous. These abnormal cells cannot fight off infection, and they interfere with the functions of other organs. – Successful treatment for leukemia depends on getting rid of all the abnormal leukocytes in the patient, allowing healthy ones to grow in their place. One way to do this is through chemotherapy, which uses potent drugs to target and kill the abnormal cells. When chemotherapy alone can’t eliminate them all, physicians sometimes turn to bone marrow transplants. • In a bone marrow transplant, the patient’s bone marrow stem cells are replaced with those from a healthy, matching donor. To do this, all of the patient’s existing bone marrow and abnormal leukocytes are first killed using a combination of chemotherapy and radiation. Next, a sample of donor bone marrow containing healthy stem cells is introduced into the patient’s bloodstream. • If the transplant is successful, the stem cells will migrate into the patient’s bone marrow and begin producing new, healthy leukocytes to replace the abnormal cells. Adult Stem Cell Transplant: Peripheral Blood Stem Cell Transplant • While most blood stem cells reside in the bone marrow, a small number are present in the bloodstream. These multipotent peripheral blood stem cells, or PBSCs, can be used just like bone marrow stem cells to treat leukemia, other cancers and various blood disorders. Since they can be obtained from drawn blood, PBSCs are easier to collect than bone marrow stem cells, which must be extracted from within bones. This makes PBSCs a less invasive treatment option than bone marrow stem cells. PBSCs are sparse in the bloodstream, however, so collecting enough to perform a transplant can pose a challenge. • Umbilical cord stem cells – The umbilical cord is the lifeline that transports nutrient- and oxygen- rich blood from the placenta to the fetus. After birth, the umbilical cord is removed from the infant, leaving a bellybutton in it’s place. – Blood from the umbilical cord contains stem cells that are genetically identical to the newborn child. – Like adult stem cells, umbilical cord stem cells are multipotent, meaning they can differentiate into only a limited range of cell types. Umbilical Cord Blood Stem Cell Transplant • Newborn infants no longer need their umbilical cords, so they have traditionally been discarded as a by-product of the birth process. In recent years, however, the multipotent-stem-cell-rich blood found in the umbilical cord has proven useful in treating the same types of health problems as those treated using bone marrow stem cells and PBSCs. • Umbilical cord blood stem cell transplants are less prone to rejection than either bone marrow or peripheral blood stem cells. This is probably because the cells have not yet developed the features that can be recognized and attacked by the recipient’s immune system. Also, because umbilical cord blood lacks well-developed immune cells, there is less chance that the transplanted cells will attack the recipient’s body, a problem called graft versus host disease. • Both the versatility and availability of umbilical cord blood stem cells makes them a potent resource for transplant therapies. Creating stem cells for research • Embryonic stem cells – Embryonic stem cell lines are established from embryos shortly after fertilization. To create an embryonic stem cell line, an embryo must be separated into individual cells. A single cell from the embryo is placed in a dish and provided with nutrients and growth factors that stimulate it to divide. The resulting cell line will continue to divide as long as it is kept in a controlled environment and provided with appropriate growth factors to prevent differentiation. • Embryonic stem cells from IVF embryos. – Human embryonic stem cell lines can be derived from embryos created through in vitro fertilization (IVF). Usually, fertilization occurs within a woman’s body, but IVF technology has made it possible to carry out fertilization and grow embryos in the laboratory. This technology has made it possible for many otherwise infertile couples to have children. In many cases, however, not all of the embryos created will be used, and the remaining embryos are frozen and stored. These embryos are potential resources for scientific research. • Embryonic stem cells from the
rapeutic cloning. – Embryonic stem cells can also be created by the same procedure used to clone whole organisms, such as Dolly the sheep. Because of its potential medical uses, this method for creating stem cells is called therapeutic cloning. – In this procedure, a nucleus from an adult donor cell is inserted into a recipient egg cell from which the nucleus has been removed. The nucleus provides all of the necessary genetic information, in the form of DNA, for a cell to function and divide. The resulting cell is then stimulated to divide as a zygote would, resulting in the growth of embryonic stem cells that are genetically identical to the adult donor cell. – Therapeutic cloning might be a viable approach to growing an exact tissue match for a patient in need – if the donor nucleus came from the patient, the resulting embryonic stem cell line would be a perfect match. • Adult stem cell lines – Adult stem cell lines isolated from mature tissues are another excellent resource for research studies. Stem Cell Therapies: What is the Recipe for Success? • Stem cell therapies involve more than simply transplanting cells into the body and waiting for them to go to work. A successful stem cell therapy requires an understanding of how stem cells work, combined with a reliable approach to ensuring that the stem cells perform the desired action in the body. • To see how therapies are developed, let’s examine a real-life example: a stem cell therapy to treat Parkinson’s disease in humans. This therapy made its debut in the late 1980s and was based on a successful treatment in a rat model of Parkinson’s disease. Since the therapy was introduced, several research groups have been evaluating its long-term success in separate trials. Step 1: Define the problem Step 2: Finding the right type of stem cell Step 3: Match the stem cells with the transplant recipient Step 4: Put the stem cells in the right place Step 5: Make the transplanted stem cells perform Step 1: Define the Problem • People who have Parkinson’s disease experience difficulty with movement, balance and speech. These problems result from the death of specialized brain cells called dopamine neurons. These cells produce dopamine, a chemical that helps control muscle movements. The effects of the disease can be treated with drugs that help increase dopamine in the brain, but there is no known cure. Researchers studying Parkinson’s disease knew that the problem was to replace the dead dopamine neurons with healthy dopamine-producing cells. Step 2: Finding the Right Type of Stem Cell To replace the dead cells, the researchers needed to find stem cells that could differentiate into dopamine neurons. Which types of stem cells could they use? Let’s evaluate their possible choices: • Blastocyst embryonic stem cells. These pluripotent cells are thought to be the most versatile type of stem cell, because they can become almost any type of cell in the body. Although their plasticity would have made them excellent candidates for the proposed therapy, researchers had not yet grown human embryonic stem cells in culture. The first success at culturing human embryonic stem cells was reported in 1998. – Therefore, although embryonic stem cells held promise for this type of therapy, they were not a feasible option at the time. • Fetal stem cells. The pluripotent stem cells found in fetal brain tissue are the natural source of dopamine neurons in the adult brain. Biologically, they were excellent candidates for the treatment. – This approach came with its own with challenges, however: the tissue needed for the treatment came from prematurely terminated human fetuses or late-stage embryos. (Technically, a human embryo is considered a fetus eight weeks after the egg is fertilized by a sperm cell.) This raised a valid ethical issue for consideration. • Umbilical cord blood stem cells. The multipotent stem cells from umbilical cord blood have the potential to turn into many different types of cells, but their natural fate is to become blood and immune cells. Also, at the time that the treatment was designed, not much was known about umbilical cord blood stem cells. Thus, they were not an option for the treatment. • Adult stem cells. There are many different types of multipotent adult stem cells, each of which is responsible for developing into the cells of a certain type of tissue. The best adult stem cell candidates for the Parkinson’s disease treatment would be those that can differentiate into dopamine neurons. At the time this treatment was being developed, however, researchers knew little about adult stem cells in the human brain. Therefore, they were not an option for the treatment. Which cells to use? Of the candidates, the best choice at the time was fetal stem cells, due to both their high potential for success and their availability. Step 3: Match the Stem Cells with the Transplant Recipient • Our immune systems attack things they don’t recognize, including cells and tissues. As with organ transplants, stem cell transplants can be rejected by the recipient’s immune system. Therefore, the transplanted stem cells must match the recipient closely enough that they won’t be recognized as intruders. To determine whether the donor is a good immunological match with the recipient, a tissue typing test is performed using blood samples from both individuals. Rejection was a concern for the researchers developing the Parkinson’s disease therapy. Previous research had told them, however, that immune responses are typically muted in the brain compared to other areas of the body. Therefore, they predicted that the fetal tissue would not trigger an intense immune response in the recipient. Step 4: Put the Stem Cells in the Right Place • Delivering stem cells to the damaged tissue will usually require a surgical procedure. This procedure must get stem cells to their target destination while causing no further injury to the recipient. Surgeons placed the cells into the brains of patients by drilling small holes in the skull and injecting the cells through a needle. They used precise imaging procedures to ensure that the injections reached the correct place in the brain. Step 5: Make the Transplanted Stem Cells Perform • After the injection, it was up to the cells to survive in their new environment and produce dopamine. • There was no guarantee that transplanted stem cells would behave as desired. If they didn’t receive or respond to the proper signals from their environment, they might have malfunctioned, formed tumors or died. • The researchers measured the patients’ progress in a couple of ways. First, they used brain imaging to determine whether the implanted cells were surviving and producing dopamine. Second, they interviewed patients to see if they experienced any changes in their symptoms. • The treatment was partly successful. The implanted cells survived and produced dopamine, and some patients reported a lessening in the severity of their symptoms. • However, some patients who underwent the procedure experienced severe side effects, including involuntary muscle twitching and jerking. While these side effects are treatable, their cause is still not clear. • While the fetal cell implant showed promise for treating patients with Parkinson’s disease, it is a milestone of progress rather than a true cure. The procedure needs to be refined so that its benefits will outweigh the risks of adverse side effects. • This work has paved the way for additional Parkinson’s disease treatments using stem cells. In the decades since the first fetal-cell implant was performed, researchers have learned much more about the biology of both embryonic and adult stem cells, both of which are now potential candidates for treating Parkinson’s disease. Some Issues In Stem Cell Research • What does stem cell research mean in my world? • New technologies have jump-started the pace of stem cell discovery in recent years. Stem cell therapies being developed today will gradually become commonplace in treating our health problems. But should we accept these new technologies without consider
ing their implications to society? For example, we might hear about the benefits of a stem cell therapy, but what are the risks? All of us – researchers, policymakers and the public – have a responsibility to explore the potential effects of stem cell research on our lives so that we can make informed decisions. For each new application of stem cell technology, we must consider: – What are the benefits? – What are the risks? – Whom will the technology help? Does it have the potential to hurt anyone? – What does this mean for me? For my family? For others around me? – Why might others not share my view? Some questions to ponder The questions raised here have no clear right or wrong answer. Instead, your response will depend on your own set of values, as well as the opinions of those around you. • How far should researchers take stem cell technologies? Just because we can do something, should we? Why or why not? • Should the government provide funding for embryonic stem cell research? Why or why not? • Should there be laws to regulate stem cell research? If so, what would they look like? For example, how would you regulate research using different types of stem cells, such as embryonic, fetal or adult stem cells? What about embryonic stem cells created using cloning technologies? • Do embryonic stem cells represent a human life? This is an ongoing debate that brings up the question of when life begins. Should the embryo or fetus have any rights in the matter? Who has the authority to decide? • Should frozen embryos created through in vitro fertilization be used to create stem cells? Why or why not?

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Category: Medical Sciences (Anatomy

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