Friday, December 14, 2007

Skin Grafts: Past, Present, and Future

Skin grafting is currently an incredibly important procedure for the thousands of people who survive devastating trauma with extreme, life-threatening burns. The practice of taking samples of skin, either from the inflicted patient or from an allogeneic source, and attaching them to the damaged area produces beneficial results that set the patient on the road to recovery. Skin grafts allow people who would otherwise be functionally or aesthetically debilitated due to their injuries to regain the utility and appearance of their epidermis. Over the past 40 years, the traditional methods of skin grafting, which involve the use of either a live or cadaver donor to directly harvest the grafts, have cemented themselves as routine, safe, and effective. Over the past 20 years, though, the pace of innovation and experimentation in the realm of skin grafting has significantly quickened. New techniques, procedures, and assistive products being used in the medical process of grafting are paving the way for more successful skin transplants and faster, more consistent healing. Although these reports of exciting research and development are focused on restorative measures for patients who have survived painful accidents, the advancements made may also be put to use in more superficial situations. There always exists the inevitable potential for medical progress to be used for superfluous, ultimately unnecessary reasons, and the case of skin grafting is no different. Many of the innovations presented in these articles could easily be transformed into the next 'hot procedure' for the more affluent members of the community.

In this blog, we provided and analyzed a collection of articles that we felt highlighted the newest, most ingenious, and most controversial innovations emerging in the field of skin grafting. The articles, appearing in various news, magazine, and scientific journal publications, widely range in topic; the use of cells which display malignant behavior in transplants, the method of actually spraying on skin cells for grafting, and the manipulation of color and tone in grafts are just some of the issues and advancements discussed in the articles themselves and our blog post responses. The format of the blog lists the articles chronologically according to their publication date—in this way, it is possible to trace the media's attention to and descriptions of the medical advancements in the field of skin grafting. Our blog responses critically analyze these lay-press representations of the innovations and their ethical and social implications.

In skin graft surgery, a variety of new techniques are being developed. These techniques are used in the actual grafting procedure to enhance post-operative care or to use skin to make other organs. One technique used on patients with extensive burns that cover 50 to 60% of their bodies involves extracting skin, allowing the epidermal cells to grow, and then spraying it back on the patient. This is different from the usual skin grafting procedure in which they stretch skin over the damaged area. This is an important advancement because it allows to autologous grafts on a wider range of patients. Post-operative care is very important in skin graft surgery, because if the graft is not a good match, it can become infected or be rejected. Another interesting practice involves the use of leeches during post-op care to encourage the flow of blood. By eliminating the pooled blood under the skin, the leeches make the graft healthier and allow it to heal and integrate with ease. The leeches also help because they have a blood thinner in their saliva and they numb the body while they feast. Another fairly recent technique that researchers are observing is the use of Therapeutic Ultrasound. From rabbit testing, TUS shows that tissue that has received this treatment has a larger number of new blood vessels and a significant increase in proliferating skin cells. In another medical arena over the last few months, skin cells have been harvested to grow the tissue needed to make blood vessels. If the use of these engineered blood vessels proves effective, this will be a revolutionary breakthrough in heart surgery; vessels will be artificially grown and the traditional harvesting of the saphenous vein or mammary artery for bypass will be unnecessary.

While embryonic stem cells have long been seen as the most effective and reliable source for skin cells, due to the plethora of moral and ethical controversy surrounding the deliberately aborting embryos, scientists and researchers are on the lookout for different sources. The makers of Cytograft in Argentina have discovered that taking a small swatch of skin from the back of the patient’s hand or the inner wrist are great sources for skin cells; once enzymes have been added to extract the necessary fibroblast cells, extracellular matrix, and serve as the framework for tissues. In America. a new kind of artificial skin, ICX-SKN, is being created from a matrix made from the skin cells that make new tissues in the body. Even the foreskin of circumcised babies has been used as a source for stem cells because they produce keratin in large amounts and never stop dividing. What is great about these new sources is that from one little piece of skin, scientists can create long grafts and engineer many new cells, ensuring that there will never be a shortage of skin cells. Now that so many sources have been discovered, the outlook for burn victims is increasingly positive.

While the use of the aforementioned mentioned skin graft techniques and procedures could be considered controversial, on a more fundamental level, the use of skin grafts is not controversial in the least. No one would begrudge a burn victim a healthier, less painful life, nor would they deny a patient suffering from ulcers the skin transplant that would cure them of their condition. The problem, then – the one true cause of controversy – is the source of the cells used to create skin grafts. There is a very limited source of skin cells that are continually viable and practical in all situations. Autologous skin transplants cannot be used on severe burn victims who lack enough healthy skin to cover their burns. Allogeneic transplants are avoided if there is a threat of an immune response, and while Epicel has recently gained FDA approval for the first xenogeneic skin transplant, using animals as possible sources of skin exposes humans to viral and bacterial infections that thus far have been restricted to other species – not to mention that animals rights activists will most certainly protest killing animals for the sake of human medical advancement. In order to overcome this lack of potent skin cells, the medical industry turned to the use of stem cells.

It is scientific fact that human neonatal foreskin fibroblasts in collagen gel form dermal skin-like tissue in vitro and that embryonic stem cells are the only human cells that are totipotent, which is to say that they can form all cell types, and have the potential to cure or treat all diseases with a significant cellular component. Therefore, it would seem ideal to use these totipotent cells in treating burn victims and other patients who require skin grafts. What makes the use of stem cells controversial is the fact that many conservative and religious groups view the destruction of a blastocyst as the murder of a human being. Thankfully, the use of two different techniques has allowed researchers to side-step this controversy.

The first method involves the harvest of adult epidermal stem cells from the skin of the patient or donor which have the capability to grow tissues with differentiated layers. These cells are attached to surgical gauze and grafted onto the patient. This creates viable transplant cells from unipotent stem cells and does not require the destruction of a blastocyst. This method is only used the most extreme cases, however. The second, more recent and exciting discovery is the creation of pluripotent stem cells from differentiated skin cells. Though this method has yet to yield transplantable skin grafts available for testing in clinical trials, and though the process of cell differentiation is currently unknown, the ability to grow any cell type without the destruction of the embryo has opened up several new avenues that can and will lead to the improved health and quality of life of burn victims everywhere.

Yet while the discovery of induced Pluripotent Stem Cells (iPS) should be greatly applauded – and the Yamanaka group congratulated with a trip to Stockholm next year – it is important to remember that this discovery, this supposed victory for both conservatives and liberals alike, did come at the terrible cost: the suffering of thousands of burn victims who would have benefited from stem cell therapy had this research been federally funded. Currently, President Bush is being lavishly praised for his continued stance against embryonic stem cell research. Supporters claim that had the president allowed such research, scientists would have had no incentive to look for alternatives to “embryo killing.” An examination of the facts, however, shows that the president deserves no such credit. Not only did President Bush limit stem cell research to a handful of aging stem cell lines, but he also prevented scientists who dared to do such research from using federally funded laboratories or equipment, or even consulting with federally supported scientists; his efforts thereby thwarted the research effort for about four to five years. Want definitive proof that the current administration’s efforts have nothing to do with the most recent breakthrough? The Yamanaka group who pioneered this method conducted their research in Japan, where they were unhindered by American regulations.

Regardless of who should ultimately receive credit, the discovery of iPS has freed skin grafting procedures and techniques from any surrounding controversies. All that remains is to look ahead and hypothesize as to what discoveries lay ahead. What advancements in skin grafting can be expected in the near future? To begin with, scientists will always have need fpr cells that grow faster – both in culture and when grafted to the patient’s skin. Continual growth would allow patients to not only develop thicker, stronger skin, but would also be extremely helpful for children who sustain severe burns and require skin that can grow as their bodies do. We can also expect future scientific discoveries to overcome immune barriers that currently prevent the widespread use of allogeneic and transgenic tissues.

All of these methods, however, are largely reactive. The future, it seems, will bring not just advancements in our ability to respond to trauma, but also in a more proactive response to treatment. If parents will soon be able to select for cancer-resistant genes – or perhaps even genes for intelligence or good looks – then it certainly may become possible to select for genes that produce thicker, healthier skin: skin that is less prone to infection (or even acne), skin that is resistant to burns and frostbite, skin that heals more quickly. At some time, improving on existing technologies or ideas may not be feasible, efficient, or even possible. If medicine reaches that point, future scientific discoveries will concern themselves not with improving these procedures and assistive products, but with improving the human species itself. Whether that would destroy our humanity, whether it would take away our highly valued human ‘essence,’ remains to be seen.