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Stem Cell Research and Potential Therapies
Medical technologies and the invention of new drugs and therapies in today's age have an extensive amount of benefit. People all over the world have benefited from the emerging technology with the invention of drugs such as vaccines and antibiotics. Along with these new developments, the science of stem cell research, which emanates from new knowledge of genetics and developmental biology studies, is also entering a new epoch of research and development that would pilot towards novel cures and palliative treatments. Although outcomes of this new breakthrough science study are still unpredictable at this level, there is an unprecedented level of knowledge to attest that the level of enthusiasm is avouched for.
Current Status: Human Stem Cell Research
Precursor cells that give rise to a diverse number tissue types are termed stem cells. Though there are varying significant distinctions, these cells have a various number of functions and pathways they differentiate into and their respective functions in an organism. Cells that give rise to a fully functional organism as well as to every cell type of the body are termed totipotent stem cells. On the contrary, cells that give rise to any tissue type but not to an organism are termed pluripotent stem cells. Multipotent cells such as mesenchymal stem cells, are slightly different, in the sense that they can only give rise to a reserved number of tissues such as muscle, fat and bone as they are more differentiated cells.
Stem cells are derived from many potential sources. Embryonic stem cells rise from the blastocysts of three-to-five day old embryos while embryonic germ cells are accumulated from the fetal tissue at a much later stage of development at the gonadal ridge. Adult stem cells on the other hand, reside in mature adult tissue and appear in very small numbers. There are a very limited number of stem cell therapies that are currently being used with the most eminent one being the stem cell transplant which is used for cancer patients. In this therapy, patients are given stem cells that can give rise to blood cells (red and white cells and platelets) in the bone marrow to heal destroyed tissues by means of high dose chemotherapy, injection of growth factors or radiation therapy. The exact completion of the research being conducted for such treatments and cures is impossible to project, but its applications and its treatments have been discussed.
-Potential applications of stem cells-
There are many potential applications for stem cells - from using stem cells to grow health tissues, to genetically manipulating stem cells for delivering genes in gene therapy approaches, to creating whole tissues in the laboratory using tissue engineering. Many scientists believe that stem cells technologies will play an important part in developing cures for diseases such as heart disease, Alzheimer's disease, Lou Gehrig's disease, diabetes and many other conditions (refer to Table 1). Currently, there is an excessive number of chronic, acute and degenerative diseases in the United States. An estimated number of 128 million people suffer from such diseases and every citizen is likely to be effected either directly or indirectly. In the United States, a total of $100 billion is being spent to treat diabetes. As research and development gets more advanced and in depth, the potential of the different kinds of stem cells and their applications will be better understood. We will now focus on some of the most promising application of stem cells to date and its examples of treatments for major diseases.
-Examples of Treatments for Major Diseases-
Type 1 Diabetes in Children.
The destruction of insulin producing cells in the pancreas leads to Type 1 diabetes which is an autoimmune disease. Current efforts to treat these patients with human islet transplantation in an effort to restore insulin secretory function (obtained from human pancreas) are limited severely by the small numbers of donated pancreas available each year combined with the toxicity of immunosuppressive drug treatments required to prevent graft rejection (Chapman, A.R, et.al.,1999). The shortage of the availability of the therapeutically effective material to transplant could be prevailed by pluripotent stem cells, which are differentiated into pancreatic cells called beta cells. Besides that, cells engineered to resist immune attacks as well as graft rejection could be engineered. Recent studies have also shown that the differentiation of human embryonic cells in cell culture are capable of producing insulin producing cells which can later be then used in transplantation.
Nervous System Disease.
The loss of nerve cells result in various number of nervous system diseases. Those that are lost cannot be replaced by division of mature nerve cells. Hence, there are no therapeutic possibilities as there is no 'new' source of functioning nerve tissue. Parkinson's disease occurs due to the death of the nerve cells that produce dopamine. Alzheimer's disease on the other hand, occurs due to the absence and death of the cells that are capable for the production of certain neurotransmitters. The death of motor nerve cells that activate muscles results in a disease termed as amyotropic lateral sclerosis. Other nervous system diseases such as stroke, spinal cord injury and brain trauma occur due to the loss or death of various number of different cells. Patients with such diseases now have the hope of being treated as new nerve tissues can be created and derived from pluripotent stem cells due to a various number of clinical experiments that have been conducted. For example, patients suffering from Parkinson's disease can be treated with the implantation of of fetal cells into their brain. Due to the lack of sufficient numbers of dopamine secreting cells, this method has not demonstrated to be very effective and hence, similar experiments using different methods such as differentiated stem cells are being used to overcome those problems. Patients suffering from Alzheimer's can now also look forward to similar approaches being conducted to replace the dead cells in the cortical and hippocampal brain regions. NeuroNova, a biotechnology company, is in the midst of experimenting different strategies of culturing adult stem cells from various donors. Once these cells have differentiated in the culture to produce the dopamine neurons which are lost in Parkinson's Disease, they are then transplanted into the patient's brain. Besides that, Neurotech, another biotech company is into the research for helping patients that suffer from gliomas. The brain endothelial cells are engineered to produce human Interleukin-2 as immunotherapy. In a recent experiment conducted in rats, the cells 'killed' the tumor cells and hence further clinical studies have begun.
Primary Immunodeficiency Disease (PID).
PID occurs in those who are born with an immune system that lacks its ability to function and is usually treated with the use of pluripotent stem cells. To date, more than 70 immune system congenital and inherited deficiencies that have been known. PID has one of the worst prognoses is a very complicated disease to be treated. Diseases such as severe combined immunodeficiency (the 'bubble boy' disease), autoimmune disease lupus and Wiskott-Aldrich Syndrome are some of the diseases that come under this category. Characterized by an unusual susceptibility to infection, these diseases are frequently associated with anemia, arthritis, and selected malignancies. However, restoration of the immune system could be possible as transplantation of stem cells could be reconstituted with the normal gene which would result in quality life and a normal life span.
Diseases of the Bone and Cartilage
Bone or cartilage cells that are deficient in numbers or defective in function could be corrected by stem cells that have been differentiated. Besides that, genetic disorders such as chondrodysplasias can also be treated with such methods. Damaged areas of the joint in cases of osteoarthritis or fractures could be introduced to cells that have been cultivated.
Patients with leukemia, a cancer that causes abnormal division of white blood cells producing immature cells, frequently requires high dose treatment such as chemotherapy to destroy the defective white blood cells. Leukemia treatments may also involve blood transfusions to replenish and replace white and red blood cells. Using stem cells to make white blood cells is becoming fairly popular and an effective way to treat cancer. Adult stem cells can also be used to treat diseases such as leukemia and sickle cell as these cells can produce various types of blood cell types. Stem cells from umbilical cord blood have also been used to provide red blood cells for sickle cell patients and patients with other blood deficiencies. Isolating stem cells from cord blood is becoming so popular that in the United States, parents can opt to pay to have cord blood stem cells frozen indefinitely should their children need them in future.
Stem cells can be used to replace dead or dying cells following various heart traumas. In the United States, heart diseases are a leading cause of death. The heart gets weak due to the weakening of the heart muscles and prevents it from beating with the normal proper strength to maintain normal blood flow. Adult cardiac muscles do not repair themselves well. Researchers at the New York Medical College and the National Human Genome Research Institute have successfully injected adult stem cells from mouse bone marrow into damaged areas of the mouse's heart (refer to figure 1) These stem cells can develop into cardiac muscle cells, form electrical connections with healthy muscle cells, and improve heart function by over 35 %. Scientists and researchers are optimistic that this method may work in humans someday. Consider a scene: in future, a surgeon many order a few grams of cardiac muscle cells from a regenerative medicine lab to transplant into a heart attack patient in much the same way that surgeons routinely order blood form a blood bank for a transfusion during this surgical procedure!
As shown in the figure in the previous page, cell culture system studies have demonstrated that the differentiation of embryonic stem cells or adult bone marrow cells can be directed into heart muscle cells. Clinical trials by Diacrin using fetal pig cells in xenotransplants have begun. For effective therapeutic results, patients that have suffered from a stroke must be treated within 24 hours and can follow up on this therapy for weeks or months after initial trauma.
With the recent advancements in stem cell technology, skin can be grown from a sample of the patient's plucked hair. When the hair is plucked, keratinocyte stem cells are removed and are further cultured to form a new skin of epidermal layer similar to the patient's own skin and also to bypass the problem of rejection by providing tissue for an autologous graft. This therapy is still being studied further in clinical trials to help patients with various number of skin problems such as venous ulcers and burn victims.
-Other Interesting Applications of Stem Cells-
The creation of chimeras - an organisms that has both human and animal cells, has brought around a big issue in today's society. The insertion of human cells into lab animals such as mice is often used in the research of stem cells. This opens the scope for scientists and researchers to study the consequences of stem cell implantation. However, this method of study has not received good response as many people are against the idea if the creation of an organism that is partly human.
New drugs could also be tested using human stem cells. For example, the safety of the drugs on differentiated cells generated from human pluripotent cells could be tested. Potential anti tumor drugs are screened using cancer cell lines. Drug testing in a wider range of cell types could be carried out due to the availability of pluripotent stem cells.
-Uses In Research-
Human biology study is a wide area of study and much is still left to be discovered. However, problems in basic and clinical biology can be well understood with the use of stem cells.
Human Developmental Biology: a New Frontage
Practical and ethical limitations often restrict the study of human developmental biology. Human ES cells may allow scientists to investigate how early human cells become committed to the major lineages of the body; how these lineages lay down the rudiments of the body's tissues and organs; and how cells within these rudiments differentiate to form the myriad functional cell types which underlie normal function in the adult (Chapman, A.R, et.al.,1999). This knowledge can be used in a wide number of fields such as cancer biology as it is now understood that cancer rises from the perturbations of normal developmental processes. The causes of birth defects and its prevention can also be studied due to the availability of human embryonic stem cells.
An unlimited supply of tissues, cells, and organs to restore functions can be created using pluripotent stem cells. These cells can be used as universal donations without regards to tissue matching compatibility in transplantation therapies. Bone marrow transplantation which is used to treat a variety of disorders such as anemia and blood disorders, is currently one of the most expensive and difficult procedures and could become safer, cheaper and more available. This would benefit patients who have lost the function of their marrow due to toxic exposure such as radiation.
Human Disease Models: Constrained by animal and cell culture models
The lack of in vitro models has restrained further studies of human diseases. Human or chimpanzee cells are perfect to culture and investigate for a very specific group of diseases such as hepatitis C and human immunodeficiency virus. Neurodegenerative diseases such as Alzheimer's give animal models a very small and fractional depiction of the disease and its process.
Chromosomal abnormalities during the very early stages of development can be explored using human pluripotent cell lines. Early childhood tumor developments can be monitored using human stem cells. These cells also can be used in the testing of candidate therapeutic drugs. Liver cells can also be produced using stem cells fir drug detoxifying uses and also presents early stages of warning in patients in order to prevent adverse reactions. Information from the Human Genome Project coupled with stem cell research will very likely deliver benefits to the society and research.
The advancement in research and technology in this new era has changed the lives of today's society. The pursuit and production of accomplishments through scientific research and discoveries offer an enormous amount of rewards for the scientists. It's a secondary question if stem cell research would have a similar effect in times to come, but the promise of this magnificent study of stem cell development is so eminent that it seems wise to consider further research in this field and how it can further improve our quality of lives. Clearly the answers to the future of this development lie in more research.
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