Stem-cell therapy

http://en.wikipedia.org/wiki/Stem-cell_therapy

Stem-cell therapy is an intervention strategy that introduces new adult stem cells into damaged tissue in order to treat disease or injury. Many medical researchers believe that stem-cell treatments have the potential to change the face of human disease and alleviate suffering.[1] The ability of stem cells to self-renew and give rise to subsequent generations with variable degrees of differentiation capacities,[2] offers significant potential for generation of tissues that can potentially replace diseased and damaged areas in the body, with minimal risk of rejection and side effects.

A number of stem-cell therapies exist, but most are at experimental stages or costly, with the notable exception of bone-marrow transplantation.[citation needed] The closer the embryo is genetically to the recipient, the less likely rejection is to occur. Use of animal embryos in humans or more commonly human embryos in lab rat models can result in transgenic cancers and additional disease transfer between species. Medical researchers anticipate that adult and embryonic stem cells will soon be able to treat cancer, Type 1 diabetes mellitus, Parkinson's disease, Huntington's disease, Celiac disease, cardiac failure, muscle damage and neurological disorders, and many others.[3] Nevertheless, before stem-cell therapeutics can be applied in the clinical setting, more research is necessary to understand stem-cell behavior upon transplantation as well as the mechanisms of stem-cell interaction with the diseased/injured microenvironment.[3]

Current treatments
Further information: Hematopoietic stem cell transplantation

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.[4][5] During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem-cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment.
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 which divide to maintain general stem cell 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). 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.[citation needed] Although the reparative process appears to initiate following trauma to the brain, 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.[6][7]

Pharmacological activation of an endogenous population of neural stem cells / neural precursor cells by soluble factors has been reported to induce powerful neuroprotection and behavioral recovery in adult rat models of neurological disorder through a signal transduction pathway involving the phosphorylation of STAT3 on the serine residue and subsequent Hes3 expression increase (STAT3-Ser/Hes3 Signaling Axis). [8][9][10]
Stem Cell Technologies

Stem cell technology gives hope of effective treatment for a variety of malignant and non-malignant diseases through the rapid developing field that combines the efforts of cell biologists, geneticists, and clinicians. Stem cells are defined as totipotent progenitor cells capable of self-renewal and multi-lineage differentiation. Stem cells survive well and show steady division in culture which then causes them the ideal targets for vitro manipulation. Research into solid tissue stem cells has not made the same progress as haematopoietic stem cells because of the difficulty of reproducing the necessary and precise 3D arrangements and tight cell-cell and cell-extracellular matrix interactions that exist in solid organs. Yet, the ability of tissue stem cells to assimilate into the tissue cytoarchitecture under the control of the host microenvironment and developmental cues, makes them ideal for cell replacement therapy. [3] [11]
Cancer

The development of gene therapy strategies for treatment of intra-cranial tumours offers much promise, and has shown to be successful in the treatment of some dogs;[12] although research in this area is still at an early stage. Using conventional techniques, brain cancer is difficult to treat because it spreads so rapidly. Researchers at the Harvard Medical School transplanted human neural stem cells into the brain of rodents that received intracranial tumours. Within days, the cells 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 the tumor mass by 81 percent. The stem cells neither differentiated nor turned tumorigenic.[13]

Some researchers believe that the key to finding a cure for cancer is to inhibit proliferation of cancer stem cells. Accordingly, current cancer treatments are designed to kill cancer cells. However, conventional chemotherapy treatments cannot discriminate between cancerous cells and others. Stem-cell therapies may serve as potential treatments for cancer.[14] Research on treating Lymphoma using adult stem cells is underway and has had human trials. Essentially, chemotherapy is used to completely destroy the patients own lymphocytes, and stem cells injected, eventually replacing the immune system of the patient with that of the healthy donor.
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 following the procedure, she could 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.[15][16]

According to the October 7, 2005 issue of The Week, University of California, Irvine researchers transplanted multipotent human fetal-derived neural stem cells into paralyzed mice, resulting in locomotor improvements four months later. The observed recovery was associated with differentiation of transplanted cells into new neurons and oligodendrocytes- the latter of which forms the myelin sheath around axons of the central nervous system, thus insulating neural impulses and facilitating communication with the brain.[17]

In January 2005, researchers at the University of Wisconsin CMadison differentiated human blastocyst stem cells into neural stem cells, then into pre-mature motor neurons, and finally into spinal motor neurons, the cell type that, in the human body, transmits messages from the brain to the spinal cord and subsequently mediates motor function in the periphery. The newly generated motor neurons exhibited electrical activity, the signature action of neurons. Lead researcher Su-Chun Zhang described the process as "[teaching] the blastocyst stem cells to change step by step, where each step has different conditions and a strict window of time."[citation needed]

Transformation of blastocyst stem cells into motor neurons had eluded researchers for decades. While Zhang's findings were a significant contribution to the field, the ability of transplanted neural cells to establish communication with neighboring cells remains unclear. Accordingly, studies using chicken embryos as a model organism can be an effective proof-of-concept experiment. If functional, the new cells could be used to treat diseases like Lou Gehrig's disease, muscular dystrophy, and spinal cord injuries.[citation needed]
Heart damage

Several clinical trials targeting heart disease have shown that adult stem-cell therapy is safe, effective, and equally efficient in treating old and recent infarcts.[18] While initial animal studies demonstrated remarkable therapeutic effects,[19][20] later clinical trials achieved only modest, though statistically significant, improvements.[21][22] Possible reasons for this discrepancy are patient age,[23] timing of treatment[24] and the recent occurrence of a myocardial infarction.[25] These obstacles may be bypassed by additional treatments to the transplanted stem cells or the patient which increase the effectiveness of the treatment[26] or by optimizing the methodology. Current studies vary greatly in cell procuring techniques, cell types, cell administration timing and procedures, and studied parameters, making it very difficult to make comparisons. Comparative studies are therefore currently needed.

Stem-cell therapy for treatment of myocardial infarction usually makes use of autologous bone marrow stem cells (a specific type or all), however other types of adult stem cells may be used, such as adipose-derived stem cells.[27] Adult stem-cell therapy for treating heart disease was commercially available in at least five continents as of 2007.[citation needed]

Possible mechanisms of recovery include:[6]

    Generation of heart muscle cells
    Stimulation of growth of new blood vessels to repopulate damaged heart tissue
    Secretion of growth factors
    Assistance via some other mechanism

It may be possible to have adult bone marrow cells differentiate into heart muscle cells.[6]

The first successful integration of human embryonic-stem-cell-derived cardiomyocytes in guinea pigs (mouse hearts beat too fast) was reported in August 2012. The contraction strength was measured four weeks after the guinea pigs underwent simulated heart attacks and cell treatment. The cells contracted synchronously with the existing cells, but it is unknown if the positive results were produced mainly from paracrine as opposed to direct electromechanical effects from the human cells. Future work will focus on how to get the cells to engraft more strongly around the scar tissue. Whether treatments from embryonic or adult bone marrow stem cells will prove more effective remains to be seen.[28]
Hematopoiesis (blood-cell formation)

The specificity of the human immune-cell repertoire is what allows the human body to defend itself from rapidly adapting antigens. However, the immune system is vulnerable to degradation upon the pathogenesis of disease, and because of the critical role that it plays in overall defense, its degradation is often fatal to the organism as a whole. Diseases of hematopoietic cells are called hematopathology. The specificity of the immune cells is what allows recognition of foreign antigens, causing further challenges in the treatment of immune disease. Identical matches between donor and recipient must be made for successful transplantation treatments, but matches are uncommon, even between first-degree relatives. Research using both hematopoietic adult stem cells and embryonic stem cells has provided insight into the possible mechanisms and methods of treatment for many of these ailments.[citation needed]

Fully mature human red blood cells may be generated ex vivo by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs 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.[29] Further research into this technique should 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 an activation of the stem cells progenitor cells. This treatment is expected to work by activating already existing stem cells on 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. Most recently, Dr. Aeron Potter of the University of California has claimed that stem-cell therapy led to a significant and visible improvement in follicular hair growth[citation needed]. Results from his experiments are under review by the journal Science (journal).
Missing teeth

In 2004, scientists at King's College London discovered a way to cultivate a complete tooth in mice[30] 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, and would be expected to grow within two months.[31] 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.[32]
Deafness

Heller has reported success in re-growing cochlea hair cells with the use of embryonic stem cells.[33]
Blindness and vision impairment

Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. "Sheets of retinal cells used by the team are harvested from aborted fetuses, which some people find objectionable." When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision.[34] 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.[35]

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 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 absence of blood vessels within the cornea makes this area a relatively easy target for transplantation. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus.

The University Hospital of New Jersey reports that the success rate for growth of new cells from transplanted stem cells varies from 25 percent to 70 percent.[36]

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.[37]

In January 2012, The Lancet published a paper by Dr. Steven Schwartz, at UCLA's Jules Stein Eye Institute, reporting two women who had gone legally blind from macular degeneration had dramatic improvements in their vision after retinal injections of human embryonic stem cells.[38] A team of doctors lead by Dr. Virender Singh Sangwan, have developed a lab free technique of regenerating stem cells using tea bag or sprinkler approach.[39]
Amyotrophic lateral sclerosis

Stem cells have resulted in significant locomotor improvements in rats with an Amyotrophic lateral sclerosis-like disease. In a rodent model that closely mimics the human form of ALS, animals were injected with a virus to kill the spinal cord motor nerves which mediate movement. Animals subsequently received stem cells in the spinal cord. Transplanted cells migrated to the sites of injury, contributed to regeneration of the ablated nerve cells, and restored locomotor function.[40]
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.[41] It was approved by Canada in May 2012.

 

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