Weizmann Institute scientists show how a "window of opportunity" could enable pig embryo tissue transplants to eventually cure genetic diseases. It doesn't sound kosher, but pig embryo tissue could eventually induce the human body to produce blood-clotting proteins for hemophilia patients and other critical substances to cure disease. Immunology Prof. Yair Reisner and doctoral student Anna Aronovich of the Weizmann Institute's Immunology Department, together with colleagues, showed how such a transplant could be made feasible in the future. The study was published recently in the Proceedings of the National Academy of Sciences (PNAS). In hemophilia, a mutated gene prevents the production of a critical blood-clotting protein. Treatments for hemophilia and other such genetic diseases, when they exist, may consist of risky blood transfusions or expensive enzyme replacement therapy. But if the body could be induced to begin producing these proteins by transplanting healthy tissue having the abilities that are lacking, this would constitute a cure. Previous attempts to treat genetic disease by transplanting (mother to daughter) a spleen, an organ that can manufacture a number of the missing proteins in some such diseases, made little headway because the spleen is home to the immune system's T-cells, which are responsible for the severe immune responses against the recipient known as graft-versus-host disease (GVHD). Reisner and colleagues revived the idea, with a twist. Over the past several years, he and his lab team have been experimenting with tissue transplanted from pig embryos, a possible substitute for human donor organs. From this, they have learned that for each type of tissue there is a "window of opportunity" during which cells taken from the developing embryo can be most successfully transplanted. Tissues taken too early, when they are still fairly undifferentiated, may form tumors, while those taken too late can be identified as foreign, causing the host to reject them. By taking spleen tissue from embryonic pigs over the course of gestation, they found that the harmful T-cells are not present in the tissue prior to the 42nd day of gestation. The scientists also found that tissue of this age exhibits optimal growth potential as well as secreting Factor 8, the blood-clotting protein missing in hemophiliacs. Thus the scientists fixed the ideal time for spleen transplantation at 42 days. Hemophiliac mice with spleen tissue transplanted from pig embryos at this time experienced completely normal blood clotting within a month or two of implantation. Although a number of problems would need to be overcome before researchers could begin to think of applying the technique to humans, the Rehovot researchersâ€š experiment is "proof of principal" - evidence that transplanted embryonic tissue, whether human or pig, could one day help the body to overcome genetic diseases.