Stem Cell Research and Testing Thesis

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In the words of Obama, "Today, with the executive order I am about to sign, we will bring the change that so many scientists and researchers, doctors and innovators, patients and loved ones have hoped for, and fought for, these past eight years: We will lift the ban on federal funding for promising embryonic stem cell research," President Obama further said. "We will vigorously support scientists who pursue this research. And we will aim for America to lead the world in the discoveries it one day may yield." [Dan Childs] With this change of stance more and more stem cell lines that were previously banned by the Bush government policy are now open for researchers increasing the scope and hastening the development of life saving stem cell therapy for a variety of chronic conditions.

Umbilical Cord Stem cells

Compared to the controversies surrounding the embryonic stem cell research, umbilical cord stem cells hold no ethical or moral dilemma. Since there is no fetus or embryo involved in the process, and the very fact that the placenta is usually a biological waste, the case for cord stem cell research is very encouraging and without any controversies. Thus far it was believed that stem cells derived from umbilical cord, being very few in number could hardly be used in lieu of bone marrow transplant for adults. However, an interesting characteristic of cord stem cells is that they can proliferate rapidly unlike adult stem cells. Furthermore, immunological rejection is much less severe in the case of cord blood transplantation compared with Peripheral blood stem cell transplant or bone marrow transplant. Even in the case of allogenic transplantations, cord blood cells are less likely to trigger immunological complications compared with adult stem cells as they are found to be immunologically downregulated. (Reduced cytokine production) [C a JONES] Further, the risk of acquiring viral and other microbial infections from cord blood transplantation is very minimal compared to adult stem cells.

Cord Blood (Treatment of Cancer)

Patients suffering from Leukemia and other serious forms of cancer have to undergo heavy irradiation, which destroys their bone marrow. Invariably such patients require bone marrow transplant, which is not so easily possible given the dearth of matching donors. Dr. Mary Laughlin, from the University hospitals of Cleveland says, "Out of every 10 adults who needs a stem cell transplant because of cancer or some other disease, only two have a brother or a sister who are perfect donor matches." [ACS] Given this bleak situation the possibility of using umbilical cord blood for grafting assumes great significance. "The other eight must search for donors. Between 3,000 and 5,000 adults die every year in the U.S. because they can't find donors. Now we know that even if you can't find a perfect bone marrow donor, umbilical cord blood can provide a successful graft."[ACS] Further, the potential for acquiring GVHD (Graft vs. Host Disease) by using cord blood is considerably low when compared to bone marrow grafting. Dr. Mary Laughlin and fellow researchers studied 68 transplant patients of whom 66 received mismatched transplant. It was found that the occurrence of GVHD among the subjects was around 38%, a rate that is significantly low compared to the usual rate of 75% observed among matched bone marrow transplants. Also, at the end of 40 months, 19 of the 66 patients managed to survive of which 18 patients were completely cured of their disease. As Dr. Herman Kattlove of the American Cancer Society says, "Survival doesn't seem to be affected by receiving a cord blood graft from an unrelated and mismatched donor. "This can be life-saving for patients who can't find a matching graft." [ACS]

Cord blood (Spinal Cord Injuries)

Spinal injuries are very crippling resulting in patients losing their neurological functions. It has been proved by several animal studies that human umbilical cord blood can be a therapeutically potent intervention for spinal injuries. Dr. Saporta, a researcher from the University of South Florida, who conducted a study on mice found out that "HUCB (human umbilical cord blood) cells have an amazing affinity for going where they are needed and take up residence within the nervous system. Our results indicate that cord blood stem cells may provide a useful and novel treatment option for patients with spinal cord injury, but more studies are needed." [USF] in another study involving 3 groups of mice it was found that the group that received HUCB along with brain derived neurotrophic factor (BDNF) showed the greatest recovery compared with the group that received only the HUCB and the control group.

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[Kuh SU et.al, 2005] However, the first major human case study is of a 39-year-old woman from South Korea. The patient who was confined to a wheelchair for the last 19 years due to a spinal injury showed significant improvement in neurological functions within 41 days of treatment with umbilical cord stem cells. (Injected directly into the injury site) . The patient was even able to walk with the help of a walker. MRI scans confirmed regeneration of spinal cord at the injured site. [Kang KS et.al, 2004]

Stem Cells in Gene Therapy

Stem cell-based gene therapy involving both Mesenchymal stem cells and Haematopoietic Stem Cells are thought to be the hope for a cure for many inherited genetic disorders. Over the last decade we have achieved huge strides in terms of our understanding of the behavior of stem cells in different tissue microenvironments. In particular, the controversies surrounding embryonic stem cell research as well as the high neoplastic potential of embryonic stem cells has motivated researchers to focus on the HSC and the MSC as other important modalities in the developing field of genetic therapy. The special feature of MSC's is their ability to suppress host immune function by modulating the dendritic T cells, which result in the production of suppressor T cells. This along with MSC's ability to target cells selectively enable them as excellent vehicles for delivery of therapeutic proteins at the appropriate tissue environment. Using a variety of techniques such as adeno viral vectors, lentivirus transduction or other non-viral methods such as electroporation or 'liposome-based transfection' it is possible to achieve effective transgene delivery. [Jakob Reiser et.al, 2005]

Several studies over the last few years have confirmed that genetically modified MSC's could be used as effective tools for the expression of recombinant proteins, the sustained production of which could reverse the progression in many cases of degenerative neural diseases such as Parkinson's, Alzheimer's, etc. Kurozumi et.al observed the effect of genetically modified MSC's that increased the synthesis of brain-derived neurotrophic factor (BDNF) in rodents recovering from ischaemia. As a control group, the researchers used rats that were only treated with unmodified MSC's. Over a 14-day period of observation it was found that the experimental group that were treated with the genetically modified MSC's (expressing BDNF) showed significant reduction in infarction in the cerebral artery compared with the control group. This clearly suggests that genetically modified MSC's that are programmed to express BDNF may increase the prognosis of stroke-affected victims and could possibly completely restore the normal functioning. [Jakob Reiser et.al, 2005]

Transduced MSC's can be used for treating blood related disorders. Several animal studies have attested to the ability of transduced MSC's to differentiate while still maintaining the ability to express the desired protein. One study involved the administration of human MSC's programmed to express hIL-3 by 'subcutaneous, intravenous, and intraperitoneal' routes. Peripheral blood count measured 3 months later showed levels of hIL-3 in the range of 100-800-page/ml, clearly indicating sustained systemic expression by Mesenchymal stem cells. [Jakob Reiser et.al, 2005]

Stem Cell Therapy for Cardiovascular Diseases

Since cardiovascular diseases represent one of the single most prevalent and life threatening conditions worldwide, stem cell-based regeneration of defective or failing cardiac tissue promises a new ray of hope for millions of patients. Already scientists have managed to successfully isolate and differentiate stem cells into cardiomyocytes. However, the problem was that stem cells being by nature pluripotent carried a high risk for contamination with other cell types. Hattan et.al (2005) used a fluorescence-activated cell seperater to isolate mice cardiomyogenic cells from mice bone marrow cells. After testing the purified cells for their gene expression the researchers then transplanted the cells to mice heart. The sorted cells started beating 3 weeks after isolation and purification and expressed genes such as alpha-skeletal actin, beta myosin, MLC-2v, and CaV1.2 that are specific for cardiomyocytes. When these isolated and expanded cells were later transplanted into the left ventricle of the adult mice they worked well with the cardiomyocytes of the recipient and lived for up to 3 months clearly suggesting that stem cell-based treatment would be an effective treatment for cases of heart muscle failures and other cardiac anomalies. [Hattan et.al, 2005] Similarly, MSC'S that are designed to differentiate into cells (expressing the mHCN2, pacemaker gene) that….....

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