One of the most challenging and exciting fields in science is that of medical research. With rapidly improving technology and increasing interest, stem cell research in particular has captured the imagination of researchers all over the world, with emphasis on the formulation of new therapies for many diseases. The discovery of (pluripotent) stem cells, fuelled by the recognition that these cells could provide many new opportunities in the field of medicine; lead to a rapid progression in the technology. Not so long ago researchers were only able to isolate pluripotent stem cells from early embryos, now they are able to reprogram somatic cells into stem-cell-like cells (IPS cells). Human embryonic stem cells have the potential to treat degenerative disease, as they have the ability to regenerate new cells to replace damaged or diseased tissue (1). One of the most amenable organs to this type of therapy is the eye. However, there are ethical dilemmas in regards to stem cell research, the most obvious one being in relation to the use of embryonic stem stems (ESCs) where a choice must be made between two moral principles as well as the fear of cloning. There are also technical issues associated with using ESC, which will also be covered in this article.
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In the most basic sense, a stem cell is a cell which has the capacity to do two things: self-renew and differentiate. This distinguishes them from other types of cells which do not have the capacity to both of these things to the same extent as an unspecialised stem cell. Therefore when a stem cell divides, each daughter cell has a choice to remain a stem cell - self renew, or to become a different type of cell with a more specialized function - differentiate (2). In many tissues/organs stem cells act as a self-repair system, dividing to replace cells that die from normal physiological circumstances as well as cells that are injured or damaged pathologically.
A stem cell can either divide symmetrically resulting in the production of two stem cells (self-renewal) or asymmetrically, resulting in the production of one stem cell and one progenitor cell on its way to becoming a differentiated cell (differentiation). Three types of asymmetrical division have been proposed. The first type is knows as environmental asymmetry, where one of the daughter cells is exposed to different environmental factors to the other daughter cell, which changes or alters the cells fate so that it must commit to differentiating or die. The second type is known as divisional asymmetry, where determinant factors found in the cell are distributed asymmetrically between daughter cells during the division, with some determinants promoting self-renewal and some pushing towards differentiation. The final type is known as population asymmetry where the balance between proliferation and differentiation is achieved at a cell population level.
Human embryonic stem cells are pluripotent and are derived from the blastocoel inner cell mass of a human embryo. Stem cells are classifies according to their varying degrees of potency (3). Pluripotent cells can differentiate and give rise to all three tissue germ layers: endoderm, mesoderm and ectoderm - these germ layers then give rise to all the tissue and organs in the body (4). However, pluripotent stem cells alone are not capable of sustaining the development of a full organism. The method of deriving stem cells from human embryos and growing them in the laboratory was discovered in 1998 by James Thomson and his colleagues (2). James Thomson drew on a host of animal studies to develop their method of culturing human ES cells (6).
Pluripotent (undifferentiated) stem cells, when injected in vivo, differentiate spontaneously into derivatives of the three germ layers thus forming a teratoma, which is a benigng tumour with components that are from all three germ layers. Since they are encapsulated, teratomas are usually benign; however there are several forms of malignant teratomas. In order to safely use pluripotent stem cells therapeutically, methods must be developed to purify the stem cell. This is why differentiated progeny are used, as there is no risk of teratoma formation
Stem cell treatments are a type of intervention strategy and up until very recently, only adult stem cells have been used successfully. This is seen notably in bone marrow transplants where hematopoietic (blood) stem cells are present in the bone marrow, and are precursors to all blood cell types (7). Other stem cell applications are the use of progenitor cells for burns and cornea injury (7). Another very promising cell type that can be used in the treatment of degenerative diseases is the Induced Pluripotent Stem cell (IPS). They are almost identical to embryonic stem cells but do not require the destruction of a human embryo to isolate them, so they are much more acceptable ethically. IPS cells are created by taking a somatic cell of the patient and using retroviral vectors to insert three or four genes that will make the cell stem-like (8). Since the IPS cell is created using the patient's own cells they will not be attacked by the patients' immune system, which is an issue when using embryonic stem cells.
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Embryonic stem cells have large potential in treating degenerative diseases as well, but due to ethical concerns and need to formulise and implement a safe method with high efficacy, it was only recently that these cells were used successfully to treat patients who suffer from macular degeneration in trial by Professor Steven Schwartz (12). The patients were blind because the retinal pigment epithelium, a layer of cells below the photoreceptors, degenerated away and thus lead to the death of the photoreceptors. The eye appears to be more amenable to stem cell therapy as it is a transparent and accessible part of the nervous system, and cells can be put in and monitored every day in non-invasive clinical exams (9). The structure of the eye, particularly the retina, also helps in successful transplantation of stem cells. The subretinal space in the eye is protected by a blood-ocular barrier, which is immune privileged (10), therefore immune rejection is unlikely to occur.
However technical and ethical issues are abundant in stem cell research. An example of this is seen in the macular regeneration trial mentioned above, and according to Schwartz et al (2012) in their trial they found that "the human ES cells should be oh high purity, classify as a differentiated cell and have no undifferentiated cells in the group, must not form teratomas (tested in vivo) or have any other unwanted side effects" (11). Ethically, embryonic stem cells pose a moral dilemma between the prevention of suffering and the respect for human life (12) and with ES cells one can't respect both principles. To isolate the ES cells and embryo must be destroyed. This is why IPS cells as an alternative to ES cells are a major advance in stem cell research. Somatic cell nuclear transfer cells are also a relatively new technology, where an embryonic stem cell is created using the patient's own somatic nucleus from any somatic cell. Technically the ES cell produced is a clone, so there is also much controversy surrounding SCNT cells.
Stem cell research is still in its early budding form and many of the problems and ethical issues we have now will be resolved in years to come. The potential and possibilities are almost endless. The success with the patients with macular degeneration is just the beginning in the profound medical journey of stem cells.