Stem cell treatments

Template:CleanupMedical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering. A number of stem cell treatments already exist, although most are still experimental and/or costly, with the notable exception of bone marrow transplantation. In the future, medical researchers anticipate being able to use technologies derived from adult and embryonic stem cell research to treat cancer, Type 1 diabetes mellitus, spinal cord injuries, and muscle damage, amongst a number of other diseases and impairments.

However, there still exists a great deal of social and scientific uncertainty surrounding embryonic stem cell research, which will only be overcome through years of intensive research and by gaining the acceptance of the public.

Furthermore, many technical difficulties remain which hinder the ultimate goals in adult stem cell therapeutics. Expanding adult stem cell populations extracted from patients remains a large problem. Also, even once these populations are expanded, implanted stem cells may not expand or grow efficiently enough to add enough corrective factor to be beneficial for treatment. These and other technical problems remain to be solved.

Current treatments

For over 30 years, bone marrow and more recently umbilical cord blood stem cells have been used to treat cancer patients with conditions such as leukemia and lymphoma. During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents not only kill the leukemia or neoplastic cells, but also those which release the stem cells from the bone marrow. It is this unfortunate side effect of the chemotherapy that the Stem Cell Transplant attempts to reverse; by introducing a Donor's healthy Stem Cells the damaged or destroyed Blood Producing Cells of the patient are replaced. In all current Stem Cell treatments obtaining Stem Cells from a matched Donor is preferable to using the patients own. If (always as a last resort and usually because no matched Donor can be found) it is deemed necessary for the patients own stem cells to be used and the patient has not stored their own collection of stem cells (umbilical cord blood), bone marrow samples must therefore be removed before chemotherapy, and are re-injected afterwards.

Potential treatments

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 administered 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 humans.

Cancer

Research injecting neural (adult) stem cells into the brains of dogs can be very successful in treating cancerous tumors. With traditional techniques brain cancer is almost impossible to treat because it spreads so rapidly. Researchers at the Harvard Medical School caused intracranial tumours in rodents. Then, they injected human neural stem cells. Within days the cells had migrated into the cancerous area and produced cytosine deaminase, an enzyme that converts a non-toxic pro-drug into a chemotheraputic agent. As a result, the injected substance was able to reduce tumor mass by 80 percent. The stem cells neither differentiated nor turned tumorigenic.

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 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 human embryonic stem cells 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 which insulates neural impulses and speeds them up, facilitating communication 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.

Heart damage

Several clinical trials targeting heart disease have shown that adult stem cell therapy is safe. However, none of these trials have proven efficacy. Adult stem cell therapy for heart disease is commercially available. Patients such as the late Jeannine Lewis, who died less than one year after treatment, and the late Hawaiian crooner Don Ho, who died within 15 months of treatment, have traveled to Thailand to receive stem cell therapy for their heart disease.

Using the patient's own bone marrow 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 has worked 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.

A Brazilian stem cell bank, has performed sample manipulation in more than 30 cell therapy procedures in cardiac patients.

Haematopoiesis (blood cell formation)

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 2007. 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 November 2004)

Missing teeth

In 2004, scientists at King's College London discovered a way to cultivate a complete tooth in mice 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.

It's 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.

In 2005, Cryopraxis a stem cell bank in Brazil, collected baby tooth stem cells and harvested different types of differentiated cell types including neurons. This technology may one day make baby tooth a good source of stem cells.

In the next three years, Paul Sharpe hopes to identify more-accessible stem cells that may be able to form not only teeth, but also--and more importantly--roots.

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 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 was carried out in 1905 on a cornea 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 impairment 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 scale. The University Hospital of New Jersey claims a success rate growing the new cells from transplanted stem cells varies from 25 percent to 70 percent.

ALS (Lou Gehrig's Disease)

In the April 4, 2001 edition of JAMA (Vol. 285, 1691-1693), 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.

Stem cell use in animals

Horses

Stem cell treatment has begun on horses, or mainly to treat injuries to the tendons, ligaments, and joints of sport horses or racehorses. Fat is harvested from the tail head and processed, and an animal may receive treatment within three days after the sample is taken. Injuries that may be treated include Degenerative Joint Disease, soft-tissue injuries, Osteochondrosis, fractures, and sub-chonral bone cysts. Currently, research is also being performed on stem cell application in laminitis and COPD.

Dogs

There is currently research being performed on the usefulness of stem cells (mesoangioblasts) in canine muscular dystrophy. This work, which has been successfully translated from mice to dogs could provide a means of treating muscular dystrophy in humans.

Controversy

Main article: Stem cell controversy

There is wide spread controversy over the use of embryonic stem cells. This controversy is over the technique used to create new embryonic stem cell lines, which often requires the destruction of the blastocyst.

Many groups oppose the use of human embryonic stem cells in research based on moral or religious objections. Others point to the success already being achieved with stem cell therapy that does not result in the destruction of a developing human being, such as the use of cord blood cells to treat spinal cord injury paralysis or recent research in turning skin fibroblasts into embryonic stem cell-like cells, and argue that research should be aimed in those avenues with a proven safety and efficacy.

Recent updates

Some scientists see shift in stem cell hopes

It was reported in the New York Times (14 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 "Many of us feel that for the next few years the most rational way forward is not to push stem cell therapies."

Stem Cell Research and Treatment in China

Stem cell research and treatment is advancing in China; state funded Chinese Companies have reportedly carried out at Shenzhen Hi-Tech Industrial Zone have successfully purified and grown embryonic, fetal, adult and umbilical cord blood stem cells.

Chinese stem cell research is not typically hampered by many of the ethical dilemmas surrounding the human embryonic stem cells in other developed nations, such as the US, UK, and Australia. Furthermore, in the US protocols for a proposed treatment are delineated and enforced by the FDA, and adhered to strongly. The period between laboratory experimentation and clinical treatment can be decades long. Researchers directly treating patients with experimental therapies can be subject to the disciplinary bodies of their institutions, rather than outside entities.

• Fiona Murray Ph.D., Debora Spar Ph.D. "Bit Player Or Powerhouse? China And Stem-Cell Research", "New England Journal Of Medicine" September 21, 2006 Accessed July 30, 2007
• Clive Cookson "Generous Staffing And Permissive Laws Aid Asia's Largest Stem Cell Effort", "Scientific American" June 27, 2005 Accessed July 30, 2007

External links

• Cell Therapy News
• whaaz, a science wiki, contains some useful information on recent developments in stem cell medicine.
• Vet-stem: Stem cell use in animals
• CalbaTech launches America's First Stem Cell Micro Bank to Harvest Adult Stem Cells
• Stem Cell and Cord Blood information database
• Stem Cell News: Treatment details and patient histories in China
• Regenerative Medicine journal