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Stem Cells

Stem Cell is a cell that has the capacity of repeated cell division while maintaining an undifferentiated state (self-renewal) and the subsequent capacity to differentiate into mature cell types (potency).
Self-renewal is the ability of stem cells to divide and produce more stem cells.

Pluripotent: meaning having the potential to differentiate into very many but not quite all cell types the make up the tissues and organs of the organism such as muscle, nerve, blood, etc. (over 200 in the body). Eg cells from a blastocyst (embryo that is 5-14 days old) Multipotent: Cells that have already differentiated, but can still form a limited number of other tissues. They are found in fetal tissue, cord blood, and adult stem cells.

differentiation, hematopoietic stem cell expansion medium, 3D matrices, and antibodies against interleukins, leukocytes, interferons, and Bcl-2 family proteins.

Potency Types
Totipotent: The master cells of humans. Each cell can develop into a new human. Eg Cells from the first few divisions of the fertilized egg only - early embryos (1 to 3 days old). This cell is totipotent, meaning it has the potential to give rise to any and all human cells, such as brain, liver, blood or heart cells. It can even give rise to an entire functional organism. The first few cell divisions in embryonic development produce more totipotent cells. After four days of embryonic cell division, the cells begin to specialize into pluripotent stem cells

Obtaining Stem Cells


How are stems cells obtained?
In order for stem cells to be cultivated, the pluripotent cells have to be alive. It must have the potential to be multiplied. The source of the cell must also be alive. This is therefore, very difficult to obtain suitable pluripotent cells. Fertility Clinics During in-vitro fertilization, clinics routinely fuse more than one egg with sperm. That way, if implanting a fertilized egg doesn't work the first time, they can try again.

Aborted Fetuses Extracting and culturing stem cells from fetuses donated by women from abortion clinics. Cloning Therapeutic cloning is useful to overcome the problem of tissue rejection and is less controversial because these embryos will not develop into complete humans as they lack the activated genes from the sperm Made to Order Fusing sperm and eggs in a petridish expressly to create embryos as sources for stem cells. Umbilical cord Stem cells also may be retrieved from umbilical cord blood. For this to occur, the mother must contact a cord blood bank before the babys birth. The cord blood bank may request that she complete a questionnaire and give a small blood sample.

Organ damage Cataracts Secondary cancers Death

Re-growing damaged skin


When a person is burnt, skin cells from an unaffected area is taken and stem cells found in these tissues are then cultured in a medium and then transplanted. Only part of the skin can be transplanted at the moment (only the outer layer) and this is very important as without the outer layer, we cannot survive. Hair follicles and Sweat glands inside the inner layer cannot be reconstructed. (As of now)

Transplantation of infected stem cells


A risk associated with fetal ventral mesencephalic (FVM) tissue transplantation is the transmission of infectious agents from donor FVM tissue. Stem cells could undergo various screening procedures that are used in clinical studies to test for infections such as hepatitis B, human T lymphocyte virus, HIV, cytomegalovirus and herpes simplex virus, ensuring a safe and reliable source of stored tissue. The risk of contamination from tissue culture and cryoprotectant media may also result from the handling of stem cells. Routine tests for common pathogens such as Staphylococcus, Streptococci, Escherichia coli and yeast will have to be carried out. IRBs should be made aware of the breadth of tests carried out to reduce the risk of transmitting infectious agents from stem cells.

Stem Cells usage and the Risks associated


The risks to research participants undergoing stem cell transplantation include tumour formation, inappropriate stem cell migration, immune rejection of transplanted stem cells, haemorrhage during neurosurgery and postoperative infection. The most common cases include;

Graft-versus-host disease Stem cell (graft) failure

Issues Surrounding Stem Cells


Techniques of Obtaining Stem cells developed to counter protests against stem cell research
PDG (Pre-implantation Genetic Diagnosis) technique To date, almost all human ESCs have been obtained by taking a human embryo and growing it into a ball of about 100 cells which contains a socalled "inner cell mass" rich in the precious ESCs. Once the ESCs have been removed with a syringe, the embryo effectively perishes. Bob Lanza and his colleagues at Advanced Cell Technology, a company in Worcester, Massachusetts, US, overcame this problem in mice by extracting just one cell from a very early 8-cell embryo called a morula. Lanza and his colleagues coaxed the single extracted cell, called a blastomere, into dividing into a colony of ESCs. They did this by putting the blastomere in contact with pre-existing ESCs. These provided the correct signals for the blastomere to become a stem cell too. But the key benefit of this technique may be that the remaining 7-cell embryos, when implanted into the wombs of female mice, developed into completely normal baby mice. Of the 47 implanted, 23 came to term, exactly the same rate as for "control" 8-cell morulas that had not had a blastomere removed. "It means we overcome the key pro-life objection, that you must destroy life to save life," says Lanza. Also, he says that the technique used to extract the blastomere is identical to that used routinely in preimplantation diagnosis during IVF to screen out embryos which are

defective and have no chance of surviving. "This procedure has been done hundreds of thousands of times, so we know it has a minimal or negligible effect on the embryo," he says. Now the race is on to try the technique in humans, and the intention is to attempt it first on non-viable embryos selected during pre-implantation diagnosis, during which a blastomere would be extracted anyway. Negative Reactions to PDG technique It places the embryo at risk of damage which could kill it. PGD is mainly a procedure to select out genetically imperfect embryos The idea that ethical fears will be allayed is a red herring. It is difficult to see any parent willing to risk having cells extracted from their own child while it is an embryo, unless it is to create stem cells in case that particular child needed them in the future

there is no evidence yet that taking stem cells will not cause harm later on the technique interferes with the natural process, and you have to ask why someone would want these stem cells. Scientists would be far better to concentrate on other areas of stem cell research such as amniotic and adult stem cells which show far more promise.

When you start mixing the obtaining of research material with a clinical test, you get into a very tricky area. If A cell was removed for PGD evaluation, and The cell was allowed to divide into two cells, and One cell was used to extract its stem cells, and The other cell died before the PGD test was complete, and If there were not a sufficient number of other embryos to test, then: The patient's care would be interrupted. She would have to delay attempts to become pregnant. it is not clear what effect this would have on children who are born after having had one of their cells removed while still an early embryo George Q Daley, a stem cell researcher at Harvard Medical School, notes that both procedures are in early stages. He said: "It's not clear it's going to work in human embryos. And in order to determine that we'll have to actually do the research on human embryos and likely destroy some in the process."

Stem Cells and future treatments!


1. Spinal cord injury. In January 2009, the Food and Drug Administration OK'd its first-ever human study of a medical treatment derived from human embryonic stem cells. The objective: help people with acute spinal cord injuries. While expected to assess only the safety of the treatment, the study also might show if the paralyzed volunteers can regain some feeling in and control over their lower extremities. 2. Diabetes. For the many Americans with type 1 diabetes, whose insulinmaking pancreatic cells have been killed off by their immune system, stem cells may be the answer. In 2008, scientists reported that they had coaxed human embryonic stem cells into becoming insulin-producing, blood sugar-regulating cells in diabetic mice. The aim: to someday do the same for people. 3. Heart disease. It's the leading cause of death in the United States, and stem cells may provide some relief. Research is underway to see if injecting the cells into the heart could help regenerate heart muscle damaged by, for example, a heart attack. Again, researchers have reported success in rodents. 4. Parkinson's disease. Stem cells may also help those who suffer from Parkinson's, a neurodegenerative disorder that can cause tremors, stiffness, and other movement and speech problems. Studies show that embryonic stem cells can give rise to the dopamine-making neurons that Parkinson's patients lack. When transplanted into rodents with a Parkinson's-like disorder, those replacement brain cells improved the animals' motor function.

5. Alzheimer's disease. Likewise, embryonic stem cells may come in handy against Alzheimer's disease, a progressive and deadly disorder that degrades and kills brain cells, leading to memory loss, cognitive decline, and behavioral problems. Stem cells may give rise to new treatments or even, some say, a cure; other experts have expressed skepticism.

Regulatory authorities relating to human embryo research


The UK was the first country in the world to regulate artificial reproduction and embryo research. It did so in the human fertilization and embryology act 1990, and this was partially revised in 2000 to allow human embryonic stem cell research and was updated in 2008 after public consultation (to gain wide spread acceptance). This law (known as legislation) imposes a strict system of controls on the creation, storage and uses of embryo outside human body. It is a criminal offense to do any of the above activities without permission ( a license) from a body known as the Human Fertilization and Embryology Authorities (HFEA) The written consent of the donors of the embryos must also be given and this must clearly show that they have consented to the uses to which their embryos will be put The HFEA receives applications from all scientists who want to conduct embryo research in the UK, including embryonic stem cell (ESC) research. The 1990 act only allows embryos to be used (and destroyed) for a number of specific purposes. Examples include fertility treatment or scientific research into human illnesses

No embryo can be kept or use d after 14days of its development. This is because the nervous system does not start to develop till then. It is possible to receive a license to create embryos solely for the purpose of medical research including their use to develop embryonic stem cell lines. In this way, it is argued, the law in the UK creates a balanced approach: it operates a framework that protects the embryo as a human organism while permitting research under strict controls.

Gene and environment interactions


There are countless examples of genes and environment interacting to produce an organisms phenotype. Some are very familiar, such as skin and hair colour; others are less so. We will take a detailed look at four examples: height hair colour MAOA causes of cancer.

Height The following are some possible answers. You may have thought of others.

1 There is some evidence that taller men have more children, which would result in a gradual change in the genetic make-up of the population. 2 Greater movements of people have resulted in less inbreeding, leading to taller people. 3 Better nutrition, especially increased protein, has resulted in greater growth of children. 4 Improved health, with a reduction in infectious diseases, has occurred through improved sanitation, clean water supplies, vaccination and antibiotics. 5 The end of child labour has allowed more energy to go into growth. 6 Better heating of houses and better quality clothing reduces the amount of energy needed to heat the body, so again more energy can go into growth. It is widely accepted that a persons height is determined by an interaction between the effects of their genes for height and environmental influences, such as diet. A person may have genes for being tall, but not achieve his or her full potential height because of malnutrition.

Making melanin The dark pigment in skin and hair is called melanin. Melanin is made in special cells, melanocytes, found in the skin and at the root of the hair in the follicle. These are activated by melanocyte-stimulating hormone (MSH). Th ere are receptors for MSH on the surface of the melanocyte cells. The melanocytes place melanin into organelles called melanosomes. The melanosomes are transferred to nearby skin and hair cells where they collect around the nucleus, protecting the DNA from harmful UV light. People with more receptors have darker skin and hair; they have more protection against sunburn. Ultraviolet (UV) light increases the amount of MSH and also of MSH receptors, making the melanocytes more active the skin to darken. Hair does not appear darker because although more melanin is produced, UV light causes chemical and physical changes to melanin and other proteins in hair cells. Hair lightens due to destruction of the melanin by UV light. Seasonal colour change Arctic foxes have brown fur in summer and white fur in winter. They must have the genes for making brown fur (which contains melanin) all the time, so how can white fur be made?

Hair colour Differences in hair colour are largely genetically determined, due to variation in the amount and type of pigment the hair contains. But the environment can influence hair colour in some cases.

The white winter coat is actually grown during the summer. It grows under the brown summer coat and is revealed when the

summer coat is moulted in autumn. The foxes produce fewer MSH receptors in the summer. Without these receptors, MSH has no effect and no melanin is made in the hair follicles.

Cancer What causes cancer?

White with dark tips To make melanin, animals use an enzyme called tyrosinase. Tyrosinase catalyses the fi rst step along a chemical pathway, changing the amino acid tyrosine into melanin. Some animals, such as Himalayan rabbits and Siamese cats, have mutant alleles for tyrosinase. The enzyme is made but it is unstable and is inactivated at normal body temperature. However, the tips of their tail, paws and ears are much darker than the rest of their bodies

One in three people in the UK will suffer from cancer at some stage in their life and, at present, one in four people dies from the disease. If we could understand the way our genetic make-up and our environment combine to cause cancer, we would be on the way to finding means of prevention and cure. Cancers occur when the rate of cell multiplication is faster than the rate of cell death.

MAOA Monoamine oxidase A is an enzyme that catalyses the breakdown of a neurotransmitter in the brain involved in the regulation of behavior, including the response to stress. It was found that some individuals have a rare mutation in the MAOA gene and produce no enzyme. They exhibit aggressive and sometimes violent behavior. Genetically modified mice which lack the MAOA gene are also aggressive. These observations led scientists to suggest there might be a connection between the gene and violent behavior but studies did not show a clear link.

This causes the growth of a tumour, often in tissues with a high rate of mitosis, such as the lung, bowel, gut or bone marrow. Cancers are caused by damage to DNA. DNA is easily damaged by physical factors such as UV light or asbestos. It can also be damaged by chemicals, known as carcinogens, which may be in the environment or can be produced by cell metabolism. Mutations can also occur when cells divide. If DNA is copied incorrectly in gamete formation, an inherited form of cancer can result. Cancer cells do not respond to the control mechanisms. Two types of gene have a role in control of the cell cycle and play a part in triggering cancer. These are: oncogenes Tumour suppressor genes.

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