Describe the use (successes and problems) of stem cells in treating cardiac disease. Include a description of the main differences between embryonic and adult stem cells. Finally, give a personal perspective on the ethical issues surrounding the use of stem cells in treatment of disease.
Use of Stem Cells in Cardiac Disease
Stem cells are characterized by two properties: pluripotency and self renewal. Stem cell therapy is one of the emerging fields of contemporary medicine and has shown the promising possibilities for the treatment of plenty of diseases. Use of stem cells in the treatment of cardiac disease is a novel approach, however bears plenty of possibilities for future. Major aim of cardiac stem cell therapy is to cure myocardial infarction by angiogenesis or myocardial regeneration. Stem cells improve the cardiovascular disease in three ways. The most common method is the local delivery or transplantation of the target tissue to replenish the diseased heart cells with normal cells. The cells might be differentiated in vivo or ex vivo. In both condition, the differentiated cells integrate into the parenchymal tissue of the surrounding area. The second mechanism of stem cell therapy for cardiac disease involves the production of progenitor cells by the endogenous production of cytokines and growth factors. (Majka M, et al, 2001)
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These factors have the tendency to hike in proliferation or survival of cells in surrounding tissue after following delivery. The role of stem cells in this case is like that of a role of a "factory". The third mechanism of stem cell therapy in cardic disease involves that they act as a autologous or heterologous vector for gene therapy (Nabel EG,2002). When stem cells are used as i gene therapy, it increases the gene targeting by natural homing or migration mechanism.
Stem cells can be delivered to heart via intravascular or extra vascular routes. The intravascular route has some limitations like poor cardiac extraction. However, this limitation might be overcome by delivery of particular cells which has the tendency to be trapped in the capillaries of myocardium.
The extra vascular route involves direct delivery of the gene or drug into the heart preferably by intramyocardial injection. This is the the most effective technique avoiding the wash out casued by blood flow. Intramyocardial injection can be carried out either by epicardial surgery or endomyocardial catheter based technique. However the limitation of this technique is that it involves the dispersion of the transfected material into a particular localised site by focal needle dissection. Intrapericardial delivery of cells is a highly efficient technique (March KI et al ,1999, Stoll HP et al , 1999), however the survival and efficacy of the the cells are unknown. This technique would be considered to be effective if the cells delivered would act as a local secretor units.
Transplantation of adult stem cells on the cardiac muscle of individuals suffering from severe angina results in the reduction of the pain and improves the ability to walk. Death rate is also reduced on the transplanted individuals than on those having no transplantation. (Northwestern University ,2009)
In a phase II clinical trial conducted on a subject having chronic heart pain and angina, involved the injection of purified stem cells (CD34+ cells) in the heart, which resulted in the improvement of pathogenic condition by growth of small vessels in the heart muscle improved microcirculation on the heart. This was the first success story of of successful stem cell transplantation for heart disease.
This study was conducted for twelve months on two groups of subjects viz experimental group and placebo group. It involved the injection of CD34+ cells at ten locations of heart muscle of experimental group followed by electrochemical mapping technology to monitor blood circulation in heart.The results obtained were very promising. This study proved that individuals own stem cells have the potency to treat his heart disease However this fact has to be verified by phase III clinical trial. Neverthless, stem cell therapy has been considered to be the first therapy to improve the pathogenic heart conditions like severe angina. (Northwestern University ,2009).
The safety and feasibility of stem cells delivery to human heart for the treatment of cardiac disease is still the area which has not been studied in depth. (Manesche P et al, 2001, Strauer BE et al, 2001). Almost all of the controlled studies which showed promising results of the stem cell therapies on cardiovascular diseases have been conducted in animals. Neverthless, the clinical trials done so far have shown promising results. But the long term safety and efficacy is still not fully assessed. Some studies involved higher number of cells to get beneficial results. The limitation of the autologous stem cell therpy is that stem cells obtained from the cardiovascular
Patient might not be as effective as those obtained from healthy person. Similarly, stem cells removed from persons with hyperlipidemia or diabetes might be unsatisfactory in function.
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Different types of stem cells used for the treatment of cardiovascular disease are: bone marrow mononuclear cells and haematopoietic cells, mesenchymal stem cells ,myoblasts, adipose stromal cells, embryonic stem cells.
Systemic or cellular approaches carried out for the treatment of cardiovascular disease is a very essential sector of medicine, that needs further investigation and advancement. It is essential to carry out a lot of investigations regarding the optimal cell type and optimal method of cell delivery to declare the stem cell therapy as a safe and effective technique for the treatment of cardiovascular diseases.
DIFFERENCES BETWEEN EMBRYONIC AND ADULT STEM CELLS
Stem cell are basically classified into: embryonic stem cells and adult stem cells. The major distinguishing feature between embryonic and adult stem cell is their capacity of differentiation. Embryonic stem cells are pluripotent and can give rise to all types of cells of body. Adult stem cells are multipotent and can differentiate into limited types of cells. Isolating embryonic stem cells in vitro from culture is relatively easier than adult stem cells because adult stem cell remain very less in the adult tissues and it is very difficult to grow and retrieve them from cell culture
Another distinguishing feature between embryonic and adult stem cells is their tendency to be accepted or rejected on transplantation. Tissues derived from embryonic stem cells have very high success rate of transplant acceptance. However, tissue derived from adult stem cells might have the chance of transplant rejection. The tendency of adult stem cells to expand in culture and getting differentiated into specific type of cells makes the patient's own stem cells to be rejected by immune system , when they are introduced into his own body. (National institute of Health , 2009).
Regarding the source of origin, embryonic stem cells originate from inner cell mass (ICM) whereas adult stem cells are prevalent in adult tisues like intestine, bone marrow, blood etc. Similarly the cell growth pattern of embryonic stem cell at confluence is non contact inhibited , whereas that of adult stem cells id contact inhibited.
Surface markers are other distinguishing features between embryonic stem cells(ESC) and adult stem cells. The embryonic stem cells contain transcription factors like oct3/4. Nanog, Rex1 and cell surface antigens like SSEA Â¾, TRA 1-60and TRA 1-81 ; whereas the adult stem cells contain tissue specific markers. They lack the transcription factors like oct Â¾, AP, telomerase and all SSEA and TRA antigens.
Thus despite plenty of similarity , embryonic stem cells and adult stem cells have plenty of contrasting features.
Personal perspective on Ethical issues surrounding the use of stem cells in treatment of disease
Regardless of the profound scope of stem cells on therapeutic use, its use on treatment of disease has been intersected by some ethical debates. The opponents of stem cell therapy have the view that use of embryonic stem is as offensive as playing with a life. They prefer to give more priority for the preservation of stem cells and tend to prevent its use on the treatment of a terrible disease. Different people might have different opinions. Hence my opinion is also very personal on this regard. As a student of life science, I would like to give emphasis on treating a terrible disease rather than ethical responsibilities to an ealrly phase of embryo in the form of stem cell. In my perspectives, embryo is just a cluster of cells unless it assumes the shape of human body. When it is manipulated in lab for the potential treatment of a terrible of disease, I would like to focus my responsibility on the treatment of a diseased human being .