"It is our belief that this procedure for antigen camouflage may have significant potential in transfusion and transplant medicine, as well as in veterinary medicine," said Mark Scott, Ph.D., associate professor of pathology and laboratory medicine. The work was presented last month at the annual meeting of the Pediatric Academic Societies.
Dr. Scott invented the technique with John Eaton, Ph.D., former head of experimental pathology at Albany Medical College, now at Baylor College of Medicine in Houston. Graduate student Kari Murad also contributed significantly to the project. The work has been conducted under a $140,000 grant to Dr. Scott from the National Institutes of Health for the study of the blood disease thalassemia.
The process involves coating the cell with a biocompatible polymer called polyethylene glycol (PEG). The PEG molecules form permanent covalent bonds on the cell's surface. This coating effectively hides the antigenic molecules on the surface of the red blood cells such that the foreign cells are not recognized by the blood recipient's antibodies.
For example, a person who has type A blood will naturally have antibodies that attach to the antigens on thesurface of type B blood cells and destroy the foreign blood. However, "the attachment of PEG to the surface of type B blood camouflages the surface of the cell so the antigens can no longer be recognized and thus prevents the destruction of the antigenically foreign red blood cells," Dr. Scott said.
Furthermore, a number of diseases, including thalassemia, that require repeated
blood transfusions are often complicated by the development of antibodies to "minor" red cell antigens. This "allosensitization" can render these patients almost impossible to transfuse. It can be a life-threatening situation. In vitro, the PEG-modified red cells appear not to trigger allosensitization and may also be useful in clinical situations where allosensitization has already
The investigators have tested the process in vitro with human, mouse, rat and
sheep red blood cells, and in vivo with mice cells. When they transfused one type of PEG-modified red blood cells into mice that had a different blood type, the treated foreign red cells were not rejected. The modified cells, while antigenically "silent," remained structurally and functionally normal and had normal in vivo survival.
Interestingly, the researchers were also able to transfuse sheep blood cells into mice and prolong the survival of these "very foreign" red cells up to 360 times that seen with untreated sheep cells from five minutes to 30 hours.
In addition to allowing blood transfusions between individuals with different blood groups, the techniques may also be useful in tissue and organ transplantation to prevent rejection, Dr. Scott said. Studies with a number of other cell types modified by this technology have shown substantial promise at preventing tissue rejection.
The worldwide rights to the technology have been acquired by Biomedical Frontiers, Inc., of Minneapolis. The company is developing techniques to apply this technology in humans, according to Dr. Bo E. Hedlund, president and CEO of Biomedical Frontiers. Human applications are still several years off, however.
The above story is based on materials provided by Johns Hopkins Children's Center. Note: Materials may be edited for content and length.
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