Because the demand for all types of organs and tissues far outweighs the supply, medical personnel—including orthopaedic surgeons—are turning to certain animal species with biologic systems that are closely compatible with human systems.
What is “xenotransplantation”?
The U.S. Food and Drug Administration (FDA) defines xenotransplantation as “any procedure that involves the transplantation, implantation, or infusion into a human recipient of either (a) live cells, tissues, or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues, or organs that have had ex vivo contact with live nonhuman animal cells, tissues, or organs.”  U.S. Food and Drug Administration, Center for Biologic Evaluation and Research: Xenotransplantation action plan. Available at: http://www.fda.gov/cber/xap/xap.htm. Accessed: October 30, 2007.
Dr. Laurencin finds that definition too restrictive and would remove the word “live” from it. When asked why he thinks the FDA definition should be modified, Dr. Laurencin provided the following example:
“Although small intestinal submucosa (SIS), for instance, is not composed of live tissue,” he said, “a cell-dependent, T-cell immune response takes place when this porcine-based tissue is implanted in humans. And, as more products enter the market, other issues may come to the fore.”
Weighing the risks, benefits
A number of commercially available xenografts for orthopaedic procedures exist, and additional products are under development. Their applications include use for bone, cartilage, and tendon repair. According to Dr. Laurencin, “Materials involving xenografts range from collagen components derived from bovine and porcine sources to deproteinated bone that can be combined with various polymers, ceramics, and autogenous tissues.”
Xenografts have a number of important benefits. Unlike human tissues, an ample supply of xenografts is available. In addition, they are easy-to-use, and provide “potentially favorable clinical performance.” However, Dr. Laurencin states that the risk of disease transmission—bacteria, viruses, and prions—may be of greatest potential concern.
Prions are infectious agents composed only of protein and “can be associated with bovine-derived tissues.” No current data suggest that any prion transmission has occurred in orthopaedic xenografts.
Another group of infectious diseases is zoonoses: diseases that can be transmitted from animals to humans. Research has shown that zoonoses are theoretically possible even in decellularized xenografts.
Dr. Laurencin also is concerned about “the risk of recombination or reassortment of various infectious agents with nonpathogenic or endogenous human infectious agents to form new pathogenic entities.”
Although he concedes that many risks and unanswered questions still surround the use of xenografts, Dr. Laurencin is a proponent of xenotransplantation—believing that “oversight is the key to public safety.”
Strengthening the oversight process
Currently, xenograft products that have been cleared for use in orthopaedic surgery by the FDA are classified as “devices.” All of these products are evaluated for their ability to “harbor potential disease-causing viruses and micro-organisms.”
To prevent these diseases from being transmitted, Dr. Laurencin would like the FDA to require manufacturers to provide more specific information on their device manufacturing and processing. “When collagen or another animal-derived material is a device component,” he writes, “the application also should identify the following:
“The species and tissue from which the animal material was derived, including the specific type of collagen or other material used.
“How the health of the herd is maintained and monitored. Is the herd closed? Is the animal material of bovine origin and, if so, is there certification that the herd is from a country free of bovine spongiform encephalopathy (BSE)?
“How the health of each animal is maintained and monitored. What is the age of the animal at sacrifice? What tests are performed to determine that the material is accessible for further processing or is pooled with material from other animals?”
He would like to see more oversight from the FDA involving new xenografts “at least until we actually have really obtained a sense of their safety.” He advocates additional oversight “in the reporting of adverse events, and postmarket surveillance. That may not be a popular belief, but I think we should exercise more caution in the beginning as new products are introduced than at the end.”
“Xenotransplantation in Orthopaedic Surgery” by Cato T. Laurencin, MD, PhD, and Saadiq El-Amin, MD, PhD, will appear in the January 2008 issue of the Journal of the AAOS.
Annie Hayashi is the senior science writer for AAOS Now. She can be reached at email@example.com
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