Potential stem cell treatments

Stem cell treatments have the potential to change the face of human disease and alleviate suffering. The ability of stem cells to self-renew and give rise to subsequent generations that can differentiate offers a large potential to culture tissues that can replace diseased and damaged tissues in the body, without the risk of rejection and side effects.

A number of stem cell treatments exist, although most are still experimental and/or costly, with the notable exception of bone marrow transplantation. Medical researchers anticipate one day being able to use technologies derived from adult and embryonic stem cell research to treat cancer, Type 1 diabetes mellitus, Parkinson’s disease, Huntington’s disease,Celiac Disease, cardiac failure, muscle damage and neurological disorders, along with many others.

1. 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 which divide and to maintain general stem cell numbers, or become progenitor cells. 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.

Stem cells may also be used to treat brain degeneration, such as in Parkinson’s and Alzheimer’s disease.

2. Cancer

Research injecting neural (adult) stem cells into the brains of dogs has shown to 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 induced intracranial tumors 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 chemotherapeutic agent. As a result, the injected substance was able to reduce tumor mass by 81 percent. The stem cells neither differentiated nor turned tumorigenic. Some researchers believe that the key to finding a cure for cancer is to inhibit cancer stem cells, where the cancer tumor originates. Currently, cancer treatments are designed to kill all cancer cells, but through this method, researchers would be able to develop drugs to specifically target these stem cells.

3. Spinal cord injury

A team of Korean researchers reported on November 25, 2003, that they had transplanted multipotent adult stem cells from umbilical cord blood to a patient suffering from a spinal cord injury and that she can now walk on her own, without difficulty. The patient had not been able to stand up for roughly 19 years. 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.

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. 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. 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.

4. Heart damage

Several clinical trials targeting heart disease have shown that adult stem cell therapy is safe and effective, and is equally efficient in old as well as recent infarcts. Adult stem cell therapy for heart disease was commercially available on at least five continents at the last count (2007).

Possible mechanisms are:

Generation of heart muscle cells
Stimulation of growth of new blood vessels that repopulate the heart tissue
Secretion of growth factors, rather than actually incorporating into the heart
Assistance via some other mechanism

It may be possible to have adult bone marrow cells differentiate into heart muscle cells.

5. 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”. 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.

6. 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.

Many challenges remain, however, before stem cells could be a choice for the replacement of missing teeth in the future.

7. Deafness

There has been success in re-growing cochlea hair cells with the use of stem cells.

8. Blindness and vision impairment

Since 2003, researchers have successfully transplanted corneal 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 cornea, 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 a cornea transplant. 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.

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.

In 2009, researchers at the University of Pittsburgh Medical center demonstrated that stem cells collected from human corneas can restore transparency without provoking a rejection response in mice with corneal damage.

In May of 2010, researchers at UC Irvine were able to successfully a grow a retina from stem cells.

9. Amyotrophic lateral sclerosis

Stem cells have cured rats with an Amyotrophic lateral sclerosis-like disease. The rats were injected with a virus to kill the spinal cord motor nerves related to leg movement, succeeded by injections of stem cells into their spinal cords. These migrated (passed through many layers of tissues) 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.

10. Graft vs. host disease and Crohn’s disease

Phase III clinical trials expected to end in second-quarter 2008 were conducted by Osiris Therapeutics using their in-development product Prochymal, derived from adult bone marrow. The target disorders of this therapeutic are graft-versus-host disease and Crohn’s disease.

11. Neural and behavioral birth defects

A team of researchers led by Prof. Joseph Yanai were able to reverse learning deficits in the offspring of pregnant mice who were exposed to heroin and the pesticide organophosphate. This was done by direct neural stem cell transplantation into the brains of the offspring. The recovery was almost 100 percent, as proved in behavioral tests in which the treated animals improved to normal behavior and learning scores after the transplantation. On the molecular level, brain chemistry of the treated animals was also restored to normal. Through the work, which was supported by the US National Institutes of Health, the US-Israel Binational Science Foundation and the Israel anti-drug authorities, the researchers discovered that the stem cells worked even in cases where most of the cells died out in the host brain.

The scientists found that before they die the neural stem cells succeed in inducing the host brain to produce large numbers of stem cells which repair the damage. These findings, which answered a major question in the stem cell research community, were published earlier this year in the leading journal, Molecular Psychiatry. Scientists are now developing procedures to administer the neural stem cells in the least invasive way possible – probably via blood vessels, making therapy practical and clinically feasible. Researchers also plan to work on developing methods to take cells from the patient’s own body, turn them into stem cells, and then transplant them back into the patient’s blood via the blood stream. Aside from decreasing the chances of immunological rejection, the approach will also eliminate the controversial ethical issues involved in the use of stem cells from human embryos.

12. Diabetes

Diabetes patients lose the function of their insulin-producing beta cells of their pancreas. Human embryonic stem cells may be grown in cell culture and stimulated to form insulin-producing cells that can be transplanted into the patient.

However, success depends on developing procedures in all required steps:[3]

* Have the cells proliferate and generate sufficient amount of tissue
* Differentiation into the right cell type
* Survival of the cells in the recipient (prevention of transplant rejection)
* Integration with the surrounding tissue in the body
* Function appropriately in long-term

13. Orthopaedics

Clinical case reports in the treatment of orthopaedic conditions have been reported. To date, the focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. Centeno et al. have published MRI evidence of increased cartilage and meniscus volume in individual human subjects. The results of trials including more patients are yet to be published making it hard to extrapolate the generalizability of these case reports. A newly published safety study published by the same group shows good safety and less complications than surgical care in a large study group of 227 patients over a 3-4 year period.

Wakitani has also published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects

14. Wound healing

In one experimental method in regenerative medicine, stem cells are used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells. A possible method for tissue regeneration in adults is to place adult stem cell “seeds” inside a tissue bed “soil” in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation. Researchers are still investigating different aspects of the “soil” tissue that are conducive to regeneration.

15. Infertility

Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells (precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis.

Human embryonic stem cells have been stimulated to form Spermatozoon-like cells, yet still slightly damaged or malformed. It could potentially treat azoospermia.

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