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Murphy, M. P., J. H. Lawson, B. M. Rapp, M. C. Dalsing, et al. “Autologous Bone Marrow Mononuclear Cell Therapy Is Safe and Promotes Amputation-Free Survival in Patients With Critical Limb Ischemia.” Journal of Vascular Surgery, v.53/6 (2011).
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Clinical Trials, U.S.: Skin Transplants
Clinical Trials, U.S.: Skin Transplants
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Clinical Trials, U.S.: Skin Transplants
Approximately 50,000 people are hospitalized each year for burns in the United States. Burn trauma remains a life-threatening and inflammatory condition that can destroy the skin and underlying tissue. After a severe thermal burn injury, skin integrity is compromised and fragile, and full thickness burns cannot heal without help. Skin transplantation using split thickness skin grafts (STSG) is the standard of care for second- and third-degree burns, and approximately 13,000 people annually require split thickness skin grafts. To prevent against rejection of a graft, skin grafts are taken from the patient (autografts).
Autografts are obtained by removing skin from a less damaged portion of the body (thigh or buttocks) and attaching it to a more damaged region. Split thickness skin grafts contain the epidermis and a small portion of the dermis. Skin grafts can be attached using staples or sutures; however, since human skin is thin and fragile after a burn injury, medical adhesives have also been used effectively. Adhesives with anti-inflammatory benefits are highly desirable to protect against uncontrolled bleeding, which is common. The use of autografts is sometimes impractical or undesirable due to the limited portion of unburned skin available, and the additional injury created at skin donor sites.
Infection is prominent among burn victims, and techniques to safely transplant skin and minimize the risk of infection are tested through clinical trials. A clinical trial is a means of testing a novel technique that may not have been utilized in the past. Clinical trials are often developed after promising laboratory research has been conducted. Clinical trials are not always successful; however, they provide an opportunity for clinicians to test a new method of treatment that may provide an improved result. A registry and result database containing information on current clinical trials in the U.S. and around the world can be accessed at www.clinicaltrials.gov, which is a service provided by the National Institutes of Health.
Stem Cell Grafting
Cell therapy has been used to treat burns since the 1980s, and significant progress has been made in the last 30 years using stem cells to treat burn injury. Rather than removing portions of donor skin from the patient, cells can now be collected from the patient’s unburned skin and used to grow skin grafts in just two to three weeks. Researchers have found that skin cell grafting is well tolerated and produces results similar to traditional split thickness skin grafting. The downside of skin cell grafting is the undesirable prolonged general anesthesia time that is often associated with the technique. Stem cells offer a realistic alternative to conventional therapies and may one day have the ability to create hair follicles and secretory glands.
Despite the attractive alternative provided by stem cells grafting, this technique was initially limited by the wait time required to grow the skin grafts and the associated cost (approximately $13,000 per 1 percent of total body surface affected). Due to the increased risk of infection that occurs during the first few weeks after a burn, cadaver grafts are temporarily applied to cover the burned skin until grafts can be grown. Recent advancements in cell therapy have provided an alternative to the use of cadaver grafts for temporary coverage.
A bioengineered skin substitute containing a near diploid neonatal human keratinocyte called StrataGraft has been demonstrated to have comparable abilities for immediate wound coverage prior to autografting. In an escalation trial funded by the National Institutes of Health, the success of autografting after two weeks of temporary coverage with either StrataGraft or cryopreserved cadaver grafts was assessed. Results from the clinical trial demonstrated that StrataGraft was comparable to cadaver grafts for temporary wound coverage and that there were no deaths or adverse events associated with using StratoGraft.
Skin Sprays
Although skin transplantation using split thickness skin grafts is still considered the standard of care for serious burn wounds, advances in tissue engineering–related research using stem cell therapy has provided alternatives. Several biotechnology companies are actively engaged in finding a solution for skin transplantation post burn injury that does not involve STSG and circumvents the wait time associated with creating skin cell grafts. For instance, skin cell spray grafting has recently been utilized to treat second-degree burn injury with success. Using only a small skin biopsy about the size of a postage stamp, surgeons can create a suspension of the stem cells from the epidermis and spray the solution directly onto the burn. The skin sample is dissolved in an enzyme solution and the cells are processed and grown before being sprayed onto the wounded area. After only three to five days, the sprayed cells have multiplied and have formed new skin.
Recell, a cell spray developed by Australian surgeon Fiona Wood to treat second-degree burns (which include the top two layers of skin), has been in widespread use in Australia and Europe since 2009. Clinical trials using Recell began in the United States in December 2009, funded by a U.S. Army grant of 1.4 million. Another cell spray tested at the University of Utah uses a concentration of the patient’s platelets and progenitor cells with calcium and thrombin. Results from application of the cell spray have been comparable to traditional skin grafting.
Mesenchymal Stem Cells and Wound Healing
The use of mesenchymal stem cells (MSCs) is also a promising type of stem cell therapy for wound healing. MSCs are found in a variety of locations throughout the body, including in bone marrow, in the umbilical cord, and in the dermal layer of the skin. MSCs are currently the easiest stem cells to harvest and grow. MSCs have been found to stimulate cell proliferation during the healing process by recruiting keratinocytes and fibroblasts to begin building new tissue.
Recent progress has been made using mesenchymal stem cells to treat the inflammation and immunosuppression that results after a burn injury has occurred, although an ideal method for administering them has not been established. MSCs may be administered through direct
