Stem Cells:

What are stem cells?

• Stem cells are the foundation cells for every organ, tissue and cell in the body. They are like a blank microchip that can be programmed to perform any number of specialized tasks.
• Stem cells are undifferentiated, “blank” cells that do not yet have a specific function.
• Under proper conditions, stem cells can divide and turn into other specialized cells such as bone, brain or blood cells.
• Stem cells are self-sustaining and can replicate themselves for long periods of time.
• While large numbers of stem cells are present in developing embryos, smaller quantities of stem cells occur in adult bone marrow and the brain.

Where do stem cells come from?

• All human beings start their lives from a single cell, called the zygote, which is formed after fertilization.
• The zygote divides and forms two cells; each of those cells divides again, and so on.
• Five days after conception, there is hollow ball of about 150 cells called the blastocyst that contains two types of cells, the trophoblast and the inner cell mass.
• Embryonic stem cells are the cells that make up the inner cell mass.
• Embryonic stem cells (pluripotent stem cells) can form all cell types in an adult.
• Stem cells can also be found in very small numbers in brain and bone marrow tissue in the adult body.
• Adult stem cells (multipotent stem cells) are typically programmed to form different cell types of their own tissue.
• Adult stem cells have not yet been identified in all vital organs.
• Stem cells can also be obtained from the umbilical cord of a newborn baby. This is an accessible source of stem cells, compared to adult tissues like the brain and bone marrow.
• Umbilical cord blood stem cells are used for stem cell transplantation to reconstitute blood cell formation (the hematopoietic system) in patients that have been irradiated or treated with specific drugs for cancer or leukemia.
• Also, in some genetic diseases, where patients have a problem forming normal blood cells, a transplantation of matched umbilical cord blood cells can give them a new blood-forming system.
• The new cells are infused into the vein of the patient and then they are able to find their way into the bone marrow, in a process called “stem cell homing”
• Stem cells in baby teeth and in amniotic fluid-the “water bath” that surrounds an unborn baby-may also have the potential to form multiple cell types.
• Baby teeth as well as umbilical stem cells are able to divide for longer times in cell cultures than most adult stem cells and may give rise to different tissues.

What diseases can be cured by using stem cells?

• Currently, researchers are investigating the use of adult, fetal and embryonic stem cells as a resource for various, specialized cell types, such as nerve cells, muscle cells, blood cells and skin cells, that can be used to treat various diseases such as:
• Parkinson’s and Alzheimer’s diseases, spinal cord injury, stroke, burns, heart disease, Type 1 diabetes, osteoarthritis, rheumatoid arthritis, muscular dystrophies and liver diseases.
• In Parkinson’s disease, stem cells may be used to form a special kind of nerve cell, a kind that secretes dopamine. These nerve cells can theoretically be transplanted into a patient where they will re-wire the brain and restore function, thus treating the patient.
• Retinal regeneration with stem cells isolated from the eyes can lead to a possible cure for damaged or diseased eyes and may one day help reverse blindness.
• Hair stem cells have also been isolated and could help people with hair loss by allowing hair cell regeneration.

What are the potential uses of human stem cells?

• Natural processes cannot replace most of the body’s specialized cells when seriously damaged or diseased.
• Stem cells can be used to generate healthy and functioning specialized cells, which can then replace diseased or dysfunctional cells.
• Cell therapy, replacing diseased cells with healthy cells, is similar to organ transplantation only it transplants cells instead of organs.
• Since there are shortages of organ donors, cell therapy will be very valuable.
• Stem cells can serve as an alternate and renewable source for specialized cells.

Benefits cell therapy:  replacing diseased cells with healthy cells:

• Adult stem cell replacement, through bone marrow transplantation with a matched donor, has been a well-established treatment for blood cancers and other blood disorders.
• However, significant toxicity and donor availability limit this approach to a minority of affected individuals.
• New possibilities for the use of adult stem cells have emerged when researchers showed that cells from the bone marrow can give rise to specialized cells in a variety of tissues as different as blood, brain, muscle, kidney, pancreas and liver.
• “Stem cells from human adult bone marrow have been successfully converted into functional brain cells, putting science closer to the possibility that one day damaged brain tissue can be repaired by implanting new cells.”
• One can imagine that one day, we will be able to isolate our own bone marrow cells, treat them and reintroduce them back into the body to renew or repair cells in a number of different organs.
• In some tissues like the brain, although stem cells exist, they are not very active, and thus do not readily respond to cell injury or damage.

Adult stem cell:

• Adult stem cells are distinct from cells isolated from embryos or fetuses and are found in tissues that have already developed, as in animals or humans after birth.
• These cells can be isolated from many tissues, including brain.
• However, the most common place is from bone marrow in the center of some bones.
• The marrow is harvested from human donors at the iliac crest (the back of the upper hip bone).
• Use of the cells from adult human bone marrow, called stromal cells, eliminates the ethical and logistical issues that arise with the use of cells from fetal tissue.
• Stem cells in adult human bone marrow are normally able to change, or differentiate, into one of three cell types: cartilage, fat cells or bone cells.
• However, researchers have been working to try to change them into nerve cells. In San Francisco, May 2004, Dr. Alexander Storch, professor of neurodegenerative diseases at the Technical University in Dresden, Germany and study author reported:
• "It's exciting to think that some day a person with Alzheimer's disease could use their own bone marrow to create brain cells that could potentially restore their functioning and make up for cells that were lost."
• Use of cells from bone marrow that would be converted and transplanted into the same person's brain eliminates ethical issues and immune-system problems that can arise when the body rejects cells from an outside source.
• More research is needed before the converted cells can be tested in humans.
• Animal studies are under way to explore the regenerative potential of the converted cells in animal models of disorders such as stroke and Parkinson's disease.
• The researchers also need to determine the best way to administer the cells into the brain.
• Some small amount of success has been achieved to convert bone marrow stem cells directly into glial and neuron cells, types of nerve cells found in the brain.
• Instead of producing nerve cells, immature neuroprogenitors were produced.
• It is hoped that these could be transplanted straight into the brain where they would, in theory, turn into fully functional glia and neuron cells.
• “Researchers found that while in suspension, the cells grow into neurospheres (small balls or aggregates of precursor brain cells) and that they expressed, or produced, the neural stem cell marker nestin”.
• "Our protocol generated a high yield of cells," Dr. Storch said. Plus, the cells grew quickly. "We calculate we'd need approximately 70 days to grow enough cells for a transplant procedure from one bone marrow biopsy. We'd have the same quantity of cells usually transplanted in studies of Parkinson's Disease," he said.
• Other benefits of this process are that the cells can be converted quickly – within a few weeks – and a small amount of bone marrow can produce a large amount of converted cells.
• Recent “stem cell plasticity” theory suggests that some adult stem cells have potential to form different cell types that may contribute to regeneration of damaged livers, kidneys, hearts, lungs and other organs.
• There are different types of stem cells found in the bone marrow, including hematopoietic stem cells, endothelial stem cells, and mesenchymal stem cells.
• Hmatopoietic stem cells form blood, endothelial stem cells form the vascular system (arteries and veins)
• Msenchymal stem cells form bone, cartilage, muscle, fat, and fibroblasts.

Stem cell lines – difference between embryonic and adult

• A stem cell line is composed of a population of cells that can replicate themselves for long periods of time in vitro, meaning out of the body.
• These cell lines are grown in incubators with specialized growth factor-containing media, at a temperature and oxygen/carbon dioxide mixture resembling that found in the mammalian body.
• Stem cell lines are composed of a population of cells that can replicate themselves for long periods of time in vitro, meaning out of the body.
• Cell lines are grown in incubators with specialized growth factor-containing media, at a temperature and oxygen/carbon dioxide mixture resembling that found in the mammalian body.
• Embryonic stem cell lines, both human and mouse, can be grown indefinitely in vitro if the correct conditions are met.
• Mouse embryonic stem cells are capable of generating any and all cells in the body, under the right conditions and are said to be have unlimited potential as far as growth and differentiation.
• The cells divide continuously in tissue culture dishes in an incubator, but at the same time maintain the ability to generate any cell type when placed into the correct environment to cause their differentiation.
• Importantly, these cells continue to retain their ability to form different, specialized cell types once they are removed from the special conditions that keep them in an undifferentiated, or unspecialized, state.
• Human embryonic stem cell lines are currently being studied to determine if they possess the same properties as mouse embryonic stem cells.

Restrictions on stem cell lines:

• A limited number of human embryonic stem cell lines have been approved for use by scientists receiving federal funds in the United States.
• In August 2001, President Bush mandated that if scientists were using federal funds, research could only be conducted on the cell lines that were already in existence, grown from fertilized eggs that were to be discarded at in vitro fertilization clinics.
• This regulation stated that no additional human stem cell lines could be generated from additional blastocysts.
• In the long term, this will limit the ability of scientists to compare the potential of human embryonic stem cell lines for tissue repair, to adult stem cells.

Obstacles to overcome before stem cell potential is realized:

• Difficult to identify stem cells from adult tissues, which contain numerous mixtures of various cells.
• The process of identifying and growing the right kind of stem cell, usually a very rare cell in the adult tissue, involves painstaking research.
• Second, once stem cells are identified and isolated, the right conditions must be developed to cause these cells to differentiate into the specialized cells. This too will require a great deal of experimentation.
• In general, embryonic and fetal stem cells are believed to be more versatile than adult stem cells.
• However, scientists are still working on developing proper conditions to differentiate embryonic stem cells into specialized cells.
• Embryonic stem cells grow very fast and great care must be taken while differentiating them into specialized cells or they can grow uncontrolled and form tumors.

Are some kinds of stem cells better than others?

• The most publicized use for stem cells is their ability to form different types of cells that can be used to restore or replace damaged tissue in patients with disease or injury.
• From studies using mice, it was found that mouse embryonic stem cells could contribute to every tissue in the adult mouse.
• It is believed that human embryonic stem cells have this property, and are called pluripotent stem cells.
• Scientists now need to compare human embryonic stem cell lines for their potential in tissue repair to that which can be accomplished from adult stem cells.
• Currently, it is not clear whether stem cells from adult tissues or umbilical cord blood are pluripotent.

What still needs to be done?

• Mouse embryonic stem cells were first described in 1981.
• It is known that under the right conditions, mouse embryonic stem cells can contribute to every tissue in the body of the mouse.
• Putting mouse embryonic stem cells into a fertilized mouse egg at the blastocyst stage, and examining the mouse that is subsequently generated uncovered this phenomenon.
• These types of experiments cannot be done with human tissues, thus the potential for human embryonic stem cells must be studied in different ways.
• The human embryonic stem cells can be studied in cell culture conditions or in special mice that are immune deficient, meaning they will not reject cells from a different species.
• Human embryonic stem cells were first described in 1998.
• The lessons learned from working with mouse embryonic stem cells are rapidly being transferred to human embryonic stem cell systems.
• Scientists are working hard to understand the properties of these cells and to understand the mechanisms that regulate their differentiation into adult cell types.
• In addition, many researchers are using these cells to set up models to study early human development and also to provide genetic and cellbased therapies for disease.
• To this end, it is hoped to better understand the causes of fetal malformations so they can be treated.
• It is also hoped that one day we will be able to produce cells in dishes, such as heart, pancreas or brain cells, to replace genetically faulty tissue or tissue damaged as a result of heart attacks, diabetes, spinal cord disorders and Parkinson’s disease.
• Cell transplantation experiments using mouse models for each of these disorders have been conducted with mouse embryonic stem cells and, in some cases, with human embryonic stem cells.
• Although it is still in its early days, promising results are emerging.
• Fetal neural stem cell derivatives have been transplanted to replace damaged cells in experiments aimed at controlling the symptoms of Parkinson’s disease with some success.
• Experiments injecting stem cells found in mouse blood vessel walls back into the blood vessels of muscles have been successful in replacing muscle fibers and returning movement to mice with muscle disorders.
• Mesenchymal stem cells have proven effective in treating mice with genetic liver disease.

Primary experiments that still remain to be performed include those

• Aimed at understanding the factors required to make embryonic stem cells differentiate into the desired cell types;
• To understand how to increase the number of stem cells that are accepted by the patient at the correct location in the body during disease; those to reduce host resistance to the new stem cells;
• Experiments to ensure that the new stem cells correctly integrate in the body to restore the proper function to the damaged tissue. [http://www.isscr.org]