Stem Cell Cord Blood Banking

Safety is the first factor to be considered when discussing the benefits of different types of stem cells.

Embryonic Cells

In addition to the moral and ethical issues involved with using embryos, embryonic stem cells have numerous challenges, including contamination, genetic instability and cancer risk. Some embryonic stem cell lines approved for research are no longer “pure” human lines since being exposed to mouse “feeder” cells to help keep them viable. The potency of these “older” approved cell lines is also increasingly compromised by time and proliferation. These cell lines accumulate genetic abnormalities as they replicate and their rapid replication with any genetic instability can create a risk of tumor development in both animal and human transplants.

Fetal Cells

The major challenge with fetal cells as used in foreign countries, is risk of graft versus host disease. Stem cells and neurons may be contaminated with blood and other tissue cells which have developed immune defenses to “foreign” cells. These fetal cells may cause immune reactions and severe health problems in the patient receiving them. In addition, the use of cortisone products to reduce immune reactivity also promotes the production of glutamate. Elevated glutamate levels are toxic to neural stem cells and can compromise the effectiveness of treatments for brain injuries and disorders.

Stem Cells Isolated from Umbilical Cord

Over 5,000 cord blood transfusions, frequently in children with leukemia, have been successfully performed throughout the world with little or no side effects since 1988. Recent research has shown that primitive stem cells from umbilical cord blood have similar powers and health promoting benefits as do embryonic stem cells but without the ethical and safety issues.

Advances are being made each day in providing greater safety to the patient. New methods of separating the stem cells from other blood components have resulted in a product that consists of only stem and progenitor cells (differentiated stem cells). Since these umbilical cord stem and progenitor cells have not yet developed mature immune defenses (ABO and HLA antigens on their surfaces), they do not induce graft versus host reactions that may occur with differentiated embryonic stem cells or bone marrow stem cells.
Larger doses of cord stem cells can also be given to further prevent immune reactions and increase effectiveness. A normal placenta and umbilical cord contains about 300,000 stem cells.

These 300,000 stem cells can be grown in tissue culture so as to reach over two million cells. These two million stem cells are used for one treatment. These increased numbers of stem cells significantly improve the results, especially in brain and spine injuries and disorders.

There are several ways that cord stem cells promote the growth of new brain tissue. Cord stem cells produce and stimulate the release of growth factors. Stem cells have been observed to fuse with established neurons as well as differentiate into neurons, astrocytes and glia cells.

Stem Cells

• Unspecialised cells found in small numbers in either embryos or tissues
• Can grow indefinitely in culture
• Primary source of all cells in the body
• Can provide an unlimited supply of defined, uniform cell types

Tissue Cells

• Specialised cells isolated from organs/tissues
• Very limited ability to grow in culture; usually don’t grow
• Limited or no ability to generate or replace cells
• Limited by the quantity of cells originally isolated and cannot be expanded

Stem cells are an important biological resource for the advancement of human medicine, because they can be grown in large quantities and yet still produce all cell types found in the body. Stem cells can provide an important benefit to humans via:

• Gene and drug discovery
• Testing the function of the large number of genes generated from the Human Genome Project
• Testing millions of potential new drugs in a ‘human environment’
• Reducing the need for animal testing
• Studying disease onset and progression (disease modelling)
• Cell therapy
• Replacing diseased or damaged cells in patient tissues
• Correcting genetic disorders (when combined with gene therapy)

Brain Damage

Stroke and traumatic brain injury lead to cell death characterized by a loss of neurons and oligodendrocytes within the brain. Healthy adult brains contain neural stem cells that divide, and act to maintain stem cells numbers or become progenitor cells. In healthy adult animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). Interestingly, in pregnancy and after injury this system appears to be regulated by growth factors and can increase the rate at which new brain matter is formed. In the case of brain injury although the reparative process appears to initiate substantial recovery is rarely observed in adults suggesting a lack of robustness. Recently, results from research conducted in rats subjected to stroke suggested that administration of drugs to increase the stem cell division rate and direct the survival and differentiation of newly formed cells could be successful. In the study referenced below, biological drugs were administerd after stroke to activate two key steps in the reparative process. Findings from this study seem to support a new strategy for the treatment of stroke using a simple elegant approach aimed at directing recovery from stroke by potentially protecting and/or regenerating new tissue. The authors found that, within weeks, recovery of brain structure is accompanied by recovery of lost limb function suggesting the potential for development of a new class of stroke therapy or brain injury therapy in man.

Spinal cord injury

A team of Korean researchers reported on November 25, 2004, that they had transplanted multipotent adult stem cells from umbilical cord blood to a patient suffering from a spinal cord injury and she can now walk on her own, without difficulty. The patient had not even been able stand up for the last 19 years. The team was co-headed by researchers at Chosun University, Seoul National University and the Seoul Cord Blood Bank (SCB). For the unprecedented clinical test, the scientists isolated adult stem cells from umbilical cord blood and then injected them into the damaged part of the spinal cord.

The Korean researchers have followed up on their original work. The original treatment was conducted in November 2004. On April 18, 2005, the researchers announced that they will be conducting a second treatment on the woman. The researchers have followed up with a case study write-up on their work. It is located in the journal Cytotherapy.

According to the October 7, 2005 issue of The Week, University of California researchers injected stem cells from aborted human fetuses into paralyzed mice, which resulted in the mice regaining the ability to move and walk four months later. The researchers discovered upon dissecting the mice that the stem cells regenerated not only the neurons, but also the cells of the myelin sheath, a layer of cells with which nerve fibers communicate with the brain (damage to which is often the cause of neurological injury in humans).

In January 2005, researchers at the University of Wisconsin-Madison differentiated human blastocyst stem cells into neural stem cells, then into the beginnings of motor neurons, and finally into spinal motor neuron cells, the cell type that, in the human body, transmits messages from the brain to the spinal cord. The newly generated motor neurons exhibited electrical activity, the signature action of neurons. Lead researcher Su-Chun Zhang described the process as “you need to teach the blastocyst stem cells to change step by step, where each step has different conditions and a strict window of time.”

Transforming blastocyst stem cells into motor neurons had eluded researchers for decades. The next step will be to test if the newly generated neurons can communicate with other cells when transplanted into a living animal; the first test will be in chicken embryos. Su-Chun said their trial-and-error study helped them learn how motor neuron cells, which are key to the nervous system, develop in the first place.

The new cells could be used to treat diseases like Lou Gehrig’s disease, muscular dystrophy, and spinal cord injuries.

Muscle damage

Adult stem cells are also apparently able to repair muscle damaged after heart attacks. Heart attacks are due to the coronary artery being blocked, starving tissue of oxygen and nutrients. Days after the attack is over, the cells try to remodel themselves in order to become able to pump harder. However, because of the decreased blood flow this attempt is futile and results in even more muscle cells weakening and dying. Researchers at Columbia-Presbyterian found that injecting bone-marrow stem cells, a form of adult stem cells, into mice which had had heart attacks induced resulted in an improvement of 33 percent in the functioning of the heart. The damaged tissue had regrown by 68 percent.

Heart damage

Several types of heart disease have been treated in clinical trials and therapy is commercially available. Patients such as Jeannine Lewis and legendary Hawaiian crooner Don Ho have traveled to Thailand to receive stem cell therapy for their heart disease.

Using the patient’s own bone marrow derived stem cells or more recently, peripheral blood-derived stem cells, Dr. Amit Patel at the University of Pittsburgh, McGowan Institute of Regenerative Medicine has shown a dramatic increase in ejection fraction for patients with congestive heart failure. He works with many other countries such as Argentina, Uruguay, Ecuador, Greece, Japan, and Thailand where he has taught minimally invasive techniques for the treatment of non-ischemic (idiopathic) and ischemic heart failure.

In Malaysia as well, Stem Cell Therapy for the heart is well established. Results are inline with results published in research papers.

Low blood supply

In December 2004, a team of researchers led by Dr. Luc Douay at the University of Paris developed a method to produce large numbers of red blood cells. The Nature Biotechnology paper, entitled Ex vivo generation of fully mature human red blood cells, describes the process: precursor red blood cells, called hematopoietic stem cells, are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red blood cell growth. Erythropoietin, a growth factor, is added, coaxing the stem cells to complete terminal differentiation into red blood cells.

Further research into this technique will have potential benefits to gene therapy, blood transfusion, and topical medicine.

Baldness

Hair follicles also contain stem cells, and some researchers predict research on these follicle stem cells may lead to successes in treating baldness through “hair multiplication,” also known as “hair cloning,” as early as 2008. This treatment is expected to work through taking stem cells from existing follicles, multiplying them in cultures, and implanting the new follicles into the scalp. Later treatments may be able to simply signal follicle stem cells to give off chemical signals to nearby follicle cells which have shrunk during the aging process, which in turn respond to these signals by regenerating and once again making healthy hair. Hair Cloning Nears Reality as Baldness Cure (WebMD Nov. 2004)

Missing teeth

In 2004, scientists at King’s College London discovered a way to cultivate a complete tooth in mice [10] and were able to grow them stand-alone in the laboratory. Researchers are confident that this technology can be used to grow live teeth in human patients.

In theory, stem cells taken from the patient could be coaxed in the lab into turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, which would be expected to take two months to grow. It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth.

Its estimated that it may take until 2009 before the technology is widely available to the general public, but the genetic research scientist behind the technique, Professor Paul Sharpe of King’s College, estimates the method could be ready to test on patients by 2007. His startup company, Odontis, fully expects to offer tooth replacement therapy by the end of the decade.

Deafness

There has been success in regrowing cochlea hair cells with the use of stem cells.

Blindness and Vision Impairment

Since 2003, researchers have successfully transplanted retinal stem cells into damaged eyes to restore vision. Using embryonic stem cells, scientists are able to grow a thin sheet of totipotent stem cells in the laboratory. When these sheets are transplanted over the damaged retina, the stem cells stimulate renewed repair, eventually restoring vision. The latest such development was in June of 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty patients using the same technique. The group, led by Dr. Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing.

In April 2005, doctors in the UK transplanted corneal stem cells from an organ donor to the cornea of Deborah Catlyn, a woman who was blinded in one eye when an acid was thrown in her eye at a nightclub. The cornea, which is the transparent window of the eye, is a particularly suitable site for transplants. In fact, the first successful human transplant. The transplant carried out in 1905 by Dr. Eduard Zirm. The recipient was Alois Gloger, a labourer who had been blinded in an accident. The cornea has the remarkable property that it does not contain any blood vessels, making it relatively easy to transplant. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus which causes vision imapairment and has no known cure even after corneal transplant. It is hoped that stem cell research will one day provide a cure to such debilitating corneal disorders.

As more research yields increasingly precise techniques, stem cell transplantation to restore vision may become viable on a large. The success rate of the procedure is currently from 20 to 70 percent , and further stem cell research is required.

ALS (Lou Gehrig’s Disease)

In the April 4th, 2001 edition of JAMA (Vol. 285, 1691-1693) [17], Drs. Gearhart and Kerr of Johns Hopkins University used stem cells to cure rats of an ALS-like disease. The rats were injected with a virus to kill the spinal cord motor nerves related to leg movement. Dr. Gearhart and Dr. Kerr then injected the spinal cords of the rats with stem cells. These migrated to the sites of injury where they were able to regenerate the dead nerve cells restoring the rats which were once again able to walk.

Some scientists see shift in stem cell hopes

It was reported in the New York Times (14th August 2006), by Nicholas Wade, that some scientists see a shift in stem cell hopes. Several mentioned that the main role of stem cells was in research. Many no longer see cell therapy as the first goal of the research, parting company with those whose near-term expectations for cell therapy remain high.

Thomas M. Jessell, a neurobiologist at Columbia University said that:

“Many of us feel that for the next few years the most rational way forward is not to push stem cell therapies”.

Stem cells differ from other kinds of cells in the body. All stem cells—regardless of their source—have three general properties: they are capable of dividing and renewing themselves for long periods; they are unspecialized; and they can give rise to specialized cell types.

Scientists are trying to understand two fundamental properties of stem cells that relate to their long-term self-renewal:

1. why can embryonic stem cells proliferate for a year or more in the laboratory without differentiating, but most adult stem cells cannot; and
2. what are the factors in living organisms that normally regulate stem cell proliferation and self-renewal?

Discovering the answers to these questions may make it possible to understand how cell proliferation is regulated during normal embryonic development or during the abnormal cell division that leads to cancer. Importantly, such information would enable scientists to grow embryonic and adult stem cells more efficiently in the laboratory.

Stem cells are unspecialized. One of the fundamental properties of a stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. A stem cell cannot work with its neighbors to pump blood through the body (like a heart muscle cell); it cannot carry molecules of oxygen through the bloodstream (like a red blood cell); and it cannot fire electrochemical signals to other cells that allow the body to move or speak (like a nerve cell). However, unspecialized stem cells can give rise to specialized cells, including heart muscle cells, blood cells, or nerve cells.

Stem cells are capable of dividing and renewing themselves for long periods. Unlike muscle cells, blood cells, or nerve cells—which do not normally replicate themselves—stem cells may replicate many times. When cells replicate themselves many times over it is called proliferation. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal.

The specific factors and conditions that allow stem cells to remain unspecialized are of great interest to scientists. It has taken scientists many years of trial and error to learn to grow stem cells in the laboratory without them spontaneously differentiating into specific cell types. For example, it took 20 years to learn how to grow human embryonic stem cells in the laboratory following the development of conditions for growing mouse stem cells. Therefore, an important area of research is understanding the signals in a mature organism that cause a stem cell population to proliferate and remain unspecialized until the cells are needed for repair of a specific tissue. Such information is critical for scientists to be able to grow large numbers of unspecialized stem cells in the laboratory for further experimentation.

Stem cells can give rise to specialized cells. When unspecialized stem cells give rise to specialized cells, the process is called differentiation. Scientists are just beginning to understand the signals inside and outside cells that trigger stem cell differentiation. The internal signals are controlled by a cell’s genes, which are interspersed across long strands of DNA, and carry coded instructions for all the structures and functions of a cell. The external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighboring cells, and certain molecules in the microenvironment.

Therefore, many questions about stem cell differentiation remain. For example, are the internal and external signals for cell differentiation similar for all kinds of stem cells? Can specific sets of signals be identified that promote differentiation into specific cell types? Addressing these questions is critical because the answers may lead scientists to find new ways of controlling stem cell differentiation in the laboratory, thereby growing cells or tissues that can be used for specific purposes including cell-based therapies.

Adult stem cells typically generate the cell types of the tissue in which they reside. A blood-forming adult stem cell in the bone marrow, for example, normally gives rise to the many types of blood cells such as red blood cells, white blood cells and platelets. Until recently, it had been thought that a blood-forming cell in the bone marrow —which is called a hematopoietic stem cell— could not give rise to the cells of a very different tissue, such as nerve cells in the brain. However, a number of experiments over the last several years have raised the possibility that stem cells from one tissue may be able to give rise to cell types of a completely different tissue, a phenomenon known as plasticity. Examples of such plasticity include blood cells becoming neurons, liver cells that can be made to produce insulin, and hematopoietic stem cells that can develop into heart muscle. Therefore, exploring the possibility of using adult stem cells for cell-based therapies has become a very active area of investigation by researchers.