Insight

Fall 2008

Enhancing Safety of Donated Tissues

The Colorado State University Animal Cancer Center (ACC) has long been a leader in the field of limb-sparing surgery, where donor bone is used to replace diseased bone in canine patients with osteosarcoma (bone cancer). Through a research partnership with AlloSource, ACC researchers are helping to make similar tissue transplants safer while advancing the science of allograft transplantation for all species.

An allograft is cells, tissues, or organs that are transplanted from one person to another (or one dog to another at the ACC). The types of allografts routinely used in human patients include skin, corneal, heart and heart valves, liver, kidney, bone and cartilage, demineralized bone matrix, ligaments and tendons. The tissues come from deceased donors and are used to enhance or save other people’s lives, from using skin grafts for burn victims to using donor bone to save the arm of a teenager, from repairing the knee of a young athlete to restoring vision when eyes are failing.

“During my research fellowship, I developed an excellent relationship with AlloSource working on several projects” said Dr. Stewart Ryan, an Assistant Professor in the Department of Clinical Sciences and member of the ACC team. “AlloSource is one of the nation’s largest tissue banks and a leader in the allograft recovery, processing and distribution field. We enjoy a free exchange of ideas that has erased the boundary between an external non-profit company and an academic institution. This has allowed us to work creatively to design research projects that help the clients of both AlloSource and the ACC.”

AlloSource and CSU have a Master Research Agreement that provides a clear framework for the ongoing research relationship with a set of ground rules covering publication rights and intellectual property. Dr. Ryan noted that the partnership has led to numerous research projects including, most recently, a study to identify potential risk factors for bacterial contamination of donor allografts, another study focusing on the translocation of bacteria following death, and a third study looking at the development of an anti-adhesion membrane for spinal surgery.

Osteochondral allografts involve the transplantation of a piece of articular cartilage and attached subchondral bone from a cadaver donor to a damaged region of the articular surface of a joint to restore function. The goal is to provide viable chondrocytes and supporting bone that will be sufficient to maintain the cartilage matrix, relieve pain, and reduce further damage to the articular surface of the joint. These types of cartilage transplant procedures are being used with increasing frequency in the treatment of individuals with disabling cartilage injury or disease.

In the statistical risk factor study, Dr. Ryan works with Dr. Paul Morley, an Assistant Professor in the Department of Clinical Sciences and epidemiologist with the Animal Population Health Institute at CSU. They are identifying potential risk factors for allograft contamination of donor tissues used in joint restoration. In the study, 850 donors were analyzed for donor factors (such as age and gender) and tissue recovery factors (including autopsy procedure performed or not, seasonal effects, time of death to cool, and time of death to recovery) to determine parameters for joint restoration donors, helping to conserve time and resources by focusing on low-risk donors. The goal of the study is to establish statistically supported guidelines for donor suitability as joint restoration tissue donors and possibly identify and modify tissue recovery practices that will increase the number of allografts produced.

“Recently, osteochondral allograft procedures have become increasingly popular in the orthopaedic community,” said Dr. Ryan. “ In an osteochondral allograft, where we are transplanting cartilage and bone, we can’t irradiate or sterilize the tissue as we can do with other allografts because these processes adversely affect the biomechanical properties of cartilage and the viability of the chondrocytes, so the risk of disease transmission is always a potential concern.“

Rigorous bacteriological testing of allograft tissues at recovery and during processing is performed to decrease this risk. Too many osteochondral allografts are rejected for transplantation because of bacterial contamination which is a poor use of the gift of donation, as well as time, financial and human resources. With this study, we hope to ensure a positive outcome for patients, as well as identify factors that will lead to better use of resources while increasing the number of allografts available for transplantation in recipients.

”In another related study, researchers are investigating the phenomenon of bacterial translocation after death and how highly infectious bacteria move through the body. Using a rodent model, bacterial solutions are tagged with a marker, fluorescently labeling the bacteria. Following death, the bacteria are followed through the body using a special imaging camera at multiple time points. Dr. Ryan noted, for example, in humans a highly infectious bacteria can migrate from the respiratory or gastrointestinal tract to regions where these bacteria are not normally found, compromising suitability of those tissues for transplantation. Tissue collection and cooling are important factors in bacterial translocation.

“Other studies have shown that if someone dies of a chronic disease, the risk of bacterial translocation is higher,” said Dr. Ryan. “If they die of trauma and there is damage to the organs that may cause an increased risk due to shaking and impact on the internal organs. Right now, we are not able to track bacteria as well as we would like, but we are working on refining the model for application as a means to trial novel decontamination procedures.”

Dr. Simon Turner, a Professor in the Department of Clinical Sciences, is working on the third project, testing an anti-adhesion membrane for spinal surgery developed by AlloSource using sheep as a model. Postoperative fibrosis (the development of scar tissue) is a natural consequence of wound healing but can cause problems when the scarring adheres to nerve roots and the dura mater (a protective layer of the meninges surrounding the brain and spinal cord) following surgery on the spinal cord. Dr. Turner’s efforts will determine the effectiveness of reducing dural adhesions using this novel allograft tissue developed by AlloSource.