Genetic diseases caused by mutations in single genes have long been the darling of gene therapy efforts. In a twist on this theme, a team from the Weizmann Institute of Science (Rehovot, Israel) has shown that embryonic spleen transplantation can correct at least one monogenic disease in mice, a proof of concept that may be applicable to humans.

Credit: ©Don Bayley

Yair Reisner and his colleagues, writing in the Proceedings of the National Academy of Sciences, describe their bid to cure hemophilia A in mice by means of fetal pig spleen tissue transplantation. Hemophilia A is a genetic disease arising from mutation in the gene for the clotting protein factor VIII (FVIII), which renders the protein unable to function and results in uncontrollable hemorrhage from injury or normal wear and tear.

Previous efforts at spleen transplantation have been plagued by graft-versus-host disease, a condition seen in bone marrow and other transplants in which residual donor T cells in the graft attack the tissue recipient. Reisner and his coworkers chose to use embryonic spleen tissue because such tissue, if derived from an early-stage fetus, is without T cells, and therefore unable to induce graft-versus-host disease.

The researchers harvested fetal pig spleen at embryonic day 42, at which point no T cells have formed, and transplanted that tissue into SCID mice deficient in the FVIII gene. Within 2–3 months, the transplanted spleens were producing enough FVIII to completely resolve all clinical manifestations of hemophilia (such as excessive bleeding). Moreover, in a separate experiment, the researchers demonstrated that the pig spleen transplants could be tolerated by immunocompetent C57BL/6 mice with the help of immune suppressors.

Taken as a whole, these results indicate that embryonic pig spleen transplants may work in humans to treat or cure patients with genetic deficiencies, such as hemophilia, phenylketonuria, or other monogenic disorders. The main obstacle to adapting these treatments to humans may be the immunosuppressant therapy required to prevent the pig spleen tissue from being rejected in humans, as such therapy carries its own health risks. For that reason, embryonic pig spleen transplants may be most suitable for diseases that have no other suitable treatment. Another possible, though morally ambiguous, variation on Reisner's technique would be to use spleen tissue taken from human fetuses aborted at an early stage, because such tissue is likely to present comparatively less chance of rejection from a human host.