Does Genetic Reprogramming Holds Promise for the Discipline of Regenerative Medicine - Research Paper Example

Regenerative Medicine Introduction Regenerative medicine involves the regenerating human cells and tissues to replace damaged ones. This field of medicine aims at accelerating the healing of damaged tissues and organs. In 2006, Yamanaka and other scientists discovered that fibroblasts of human and mice could generate pluripotent cells (iPSC means Induced Pluripotent Stem Cells) when genetically reprogrammed (Giordano 307). The genetic programming makes these somatic cells to lose characters of their specific tissues and become pluripotent. These cells are similar to embryonic cells in that they can differentiate into the various body cells under favorable conditions. The advantage of iPSCs cells over the embryonic cells is that they do not need embryos during production. This makes the technology ethically acceptable. IPSCs cells production involves inserting of stem cell associated genes into specialized somatic cells using viral vectors (Xiong et al 1). Genetic engineers hopefully believe iPSCs cells will initiate the production of cells or tissue from a patient that will repair the damaged tissues. The cells regenerated through induced pluripotent stem cell method are most suitable in restoring damaged cells and tissues. This is because the patient’s immune system will readily tolerate them. This will eliminate the problem of graft rejection exhibited in xenografts or isografts. Elimination of immune suppressive drugs on patients usually does happen. Despite all these seemingly possible setbacks, induced pluripotent stem cells have proofed to be the future of the regenerative medicine. Patients suffering from cardiovascular disease and other disorders will find cure after the establishment of this technology. Application of iPSCs in treatment of cardiovascular disease Cardiovascular disease affects the cardiovascular system (the heart and the blood vessels). These diseases include coronary heart disease, stroke, congestive heart failure, pulmonary embolism among others. The iPSCs technology promises a positive break through to the medicine world (Amit &Joseph112). The ability to induce adult specific cells into stem cell without use of embryo enables clinicians to change other cells from a patient. The body recognizes the cells as self and therefore no rejection can occur. Researchers are successfully modeling many cardiovascular diseases by this technology. The improved understanding of the cardiovascular diseases provides a better treatment in the medicine world. Formation of cardiomyocytes Reprogramming of somatic cells into iPSCs is by integrating or non-integrating method. The integrating method uses viral vector while the non-integrating method uses a plasmid to deliver the genes. For cardiovascular disease treatment, the most suitable is the non-integrating method. Reprogramming of the fibroblasts of the dermis of the patient produces the iPSCs for use. A method called embroyoid body differentiation turns the iPSCs to revolve into cardiomyocytes (Nelson et al 2). The cardiac cells produced this way show the same characteristics of human cardiac cells although they may differ in morphology. To determine functionality of the iPSCs, cardiomyocytes researchers use molecular techniques such as immunocytochemistry and polymerase chain reaction techniques (Amit & Joseph117). The cardiomyocytes formed from patient cells posses the mutations that cause disease in the patient. These cells serve as the model for the disease and therefore further investigations are possible. Modeling of inherited cardiovascular diseases is very important in determining its cure. The iPSCs cardiomyocytes (heart muscle cells) provide the best model for these diseases. The iPSCs provide insights to concerns of heart repair. This technology is a potential source of cells for repairing the heart and blood vessels. Studies done by Li and co-researchers gave the evidence that induced pluripotent stem cells would provide unlimited resources for transplantation. This form of tissue transplant does not involve immune rejections because of the specificity of the cells. The draw back of the clinical application of the technology in heart repair is the recognized uncertain reactions of the iPSCs (Nelson et al 4). However, investigations show that this technology is succeeding in some way. For example, iPSCs treatment increased the wall of a thin ventricle and produced cardiac endothelium and smooth muscles. The human heart cells do not regenerate once damage occurs to it. The iPSCs therefore will provide the much needed solution for heart attacks. Furthermore, the iPSCs are essential in testing drugs for cardiac disease. The law demands the testing of drugs and other human products before approval for human consumption. Pharmaceutical firms and researchers used the heart cells produced through iPSCs technology to test cardiac drugs. iPSCs cardiomyocytes enable reliable drug testing. The test shows the effect of the drug on that particular patient. In this way, clinicians easily establish the expected response of the patient’s body to the drug (Zhang et al 3). They also learn about any undesirable side effects of the drug before the patient uses it. This can potentially reduce deaths because even a negative response of a patient’s body to a cardiac drug can be fatal. This is very useful to medics, despite the time consuming procedures involved. The advancement of the medical field will remain insignificant the time when heart failure will cease. iPSCs cells are giving positive results of the treatment of heart failure.This are the leading cause of sudden death worldwide. The technology that is shading some light to this problem needs support from all organizations and countries. The cause of heart failure is the degeneration and fatigue of the cardiac muscles. Regeneration of cardiac muscle cells using induced pluripotent stem cells is under intense investigation. Using special cell delivery techniques scientist are trying to determine the effectiveness of cardiac cells derived from iPSCs in cardiac muscle repair (Nelson et al 5). The cardiac muscle cells from induced pluripotent cells will also be of use in understanding the barriers to the treatment of specific patients. The application of iPSCs in regenerative medicine There are controversies on whether induced pluripotent stem cells can serve as a source of tissue in the regenerative medicine. Investigators support the idea of reprogramming cells to become pluripontent cells for tissues and organs. Evidence shows that with further investigations, iPSCs can enhance the regenerative medicine and provide cure for many diseases and disorders. The use of iPSCs will reduce immune rejection of grafts. Regenerative medicine aims at repairing, regenerating, and replacing damaged body organs and tissues. The iPSCs cells produced from the same individual do not face immune rejection. The immune system is unlikely to mount into immune responses to iPSCs cells used to repair tissues. However, research conducted by biologists in UC San Diego proved otherwise. They discovered some immune rejection of iPSCs. They found out that the immune system of one strain of mice rejected induced pluripotent stem cells of same strain of mice (Amit & Joseph 125). The cause of the response is due to abnormal expression of gene during the differentiation of the induced pluripotent stem cell. The iPSCs can treat mascular degeneration. Scientists of the University of London carried out experiments on mice with deformed retinas. A mutant gene produced blind rats due to lack of retinal photoreceptors. Insertion of iPSCs derived from pigmented retinal epithelium restored the sight of the mice. This proved the ability of induced pluripotent stem cells to treat age related loss of vision. This loss is attributed to the damage of the retina and with further research, can reverse of the condition is possible (Okita et al 8).The clinical trial of retinal regeneration is under investigations. The recent experiments show restoration function for completely damaged retina. This is making the induced pluripotent stem cells consideration in clinical trials necessary. Scientific reporters said that the treatment of muscle degeneration using induced pluripotent cells would undergo further clinical testing. Japan followed by clinical trial therapies as well. Studies carried out by Dr Ramiro and co-researchers of the University of Nottingham exposed the possibility of formation of gametes from induced pluripotent stem cells in the future. They used the knowledge on metastable states of pluripotency in modeling the development transitions of embryo. They studied the path of differentiation of iPSCs into precursors of germ cell. The study involved different species where they determined the nature and program of germ cells. This understanding is crucial in developing technologies that will produce artificial gametes. Artificial gametes will significantly enhance reproductive health. With advanced research, they can be generation of functional neuron from induced pluripotent stem cells. Investigators of the New York stem cell foundation successfully regenerated neuron cells from skin fibroblasts. In terms of clinical application, the advancement in the technology gives hope for cure of neural diseases. By introducing specific genetic factors into the fibroblasts, they turned into pluripotent cells, which then became natural neuron cells (Zhang et al 13). The cells can grow into neurons and scientist can use them to determine the development and progression of neural diseases. The neurons formed can as well replace damaged nerves and dendrites. Scientists are constantly supporting the progress iPSCs technology because its success will be a breakthrough to the regenerative medicine. Limitations and challenges of induced pluripotent stem cells Despite the promising future of the iPSCs technology, it faces many challenges. Among the many risks is that of mutations of the induced stem cells. During the insertion of the stem cell, related genes using the various factors, some genetic changes occur. Consequently, the iPSCs cells formed are not genetically similar to the original adult cell. This factor makes the regenerated cells unsuitable for any medicinal use like repair of tissues or drug testing. In case of use in repairing or replacing tissues, the immune system recognizes them, as non-self, and immune response would then destroy the cells (Giordano 310). Some viral vectors used in this technology are retroviruses. There is therefore the risk of tumor induction. Some of the tumors may be cancerous posing fears of introducing these cells into the human body. Recent research espouses that induced stem cells are likely to form cancer cells. Unlike the natural somatic cells where only one or few cells become cancerous, a large number of induced stem cells may become cancerous. The viral vector replicates as part of the cell DNA and thus expressing some undesired characteristics (Okita et al10). According to Olga, stem cell biologists, investing more time on research might give a workable solution to the mutations of induced cells. This will address the issue of tumor formations before any significant application of these cells in regenerative therapy. The integration of the iPSCs cells with the exiting tissue or organ, if used in therapeutic treatment, is still a challenge. This will determine the success of the regenerative therapy. Body organs have a balance of different type of cells in that particular organ and strategic positioning in parts of the organ (Xiong et al 12). Scientists have not yet determined whether transplanted cell types can control their numbers to match with the number needed by the recipient organ or tissue. For organs such as the heart, kidney, liver, and lungs, it is important for the transplant cells to function in unison with the existing cells. This is a research that investigators are yet to factor. The other challenge of this technology is the incomplete reprogramming of the target cell. In some cases, there is no complete change of the somatic cell into a pluripontent stem cell. Incomplete transformation of the cells limit its ability to differentiate into any cell type as required. Some disorders like Fibrodysplasia Ossificants Progressive (FOP) suppress the generation of pluripotent stem cells. The skin disorder causes ossification of tissues that are soft. The original method used in reprogramming show a lot of inefficiency. Only 1% of the adult cells become pluripotent at the end of the reprogramming process (Amit & Joseph 122). Low efficiency of reprogramming calls for research of ways of increasing the transformation efficiency. However, scientists are coming up with ways of overcoming the challenges. For instance, the use adenoviruses vectors instead of retroviruses. Using of adenovirus to insert the reprogramming genes into the somatic cells will reduce the risk of tumors. This will also ensure proper integration of the genes in the virus into the host cell DNA. Transfection of naked DNA into the host genome is another alternative method of inserting transformation genes into somatic cells (Okita et al 12). The limitation of these two ways is the low reprogramming efficiency. Other scientist suggests pure chemical reprogramming. This is likely to ensure production of safer induced pluripotent cells. The use of chemicals such as methyltransferase may enhance the efficiency of reprogramming. Summary A new promising technology, which involves the conversion of adult differentiated cells into pluripotent stem cell, is emerging. A professor in medicine, Yamanaka, and other clinical researchers of Tokyo succeeded in inducing pluripotency into somatic cells by inserting stem cell genes into them. The induced pluripotent stem cells have the ability to form any cell line. The discovery received support from the regenerative medicine field. The aim of regenerative medicine is to regenerate tissues and organs in order to replace or restore the damaged ones. Organ and tissue damage result mainly from aging .Once restored, the organs will function normally thus ensuring good health. IPSCs technology is a potential source of Cells needed for regenerative medicine. The regeneration of cells from a patient and using them on the same individual reduces the risk of immune rejection. The clinical application of these cells is still undergoing more research. However, the technology is advancing year by year. Experimentations are showing the success of this new biotechnology in diagnosing and treating cardiovascular diseases. Cardiac cells formed from iPSCs are proving models for testing drugs and studying different cardiovascular diseases. Many limitations and challenges face the use of the induced pluripotent cells in clinical therapies. With more investigation, these induced stem cells may greatly improve disease management and treatment as well as organ and tissue restoration. This is well illustrated in the diagram below. Thank you Available at: https://annals.org/data/Journals/AIM/20367/10FF2.jpeg (accessed April 24 2013) Work cited Amit, M, and Joseph Itskovitz-Eldor. Atlas of Human Pluripotent Stem Cells: Derivation and Culturing. New York: Humana Press, 2012. Print. Giordano, Antonio, and Marcella Macaluso. Cancer Epigenetics: Biomolecular Therapeutics for Human Cancer. Hoboken, N.J: Wiley-Blackwell, 2011. Print. Nelson, T.J. et al. Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells.Epub, 2009. Print Okita, K, et al. Generation of mouse induced pluripotent stem cells without viral vectors. Epub, 2008. Print. Xiong Q, et al. Functional consequences of human induced pluripotent stem celltherapy: myocardial ATP Tunover Rate in the in vivo swine hearts with post-infarction remodeling.. Epub, 2013. Print. Zhang, J. et al. Fuctional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res, 2009. Print. Read More