October 2, 1998 

John Iacomimi, PhD, of the Transplantation Biology
Research Center

MGH team makes advance toward cross-species transplantation

Researchers at the MGH Transplantation Biology Research Center (TBRC) have made an important step toward inducing the human immune system to accept transplanted organs from another species. In the Sept. 18 issue of Science, John Iacomini, PhD, of the TBRC, and his colleagues describe a gene therapy approach that may be able to suppress production of natural antibodies that mediate rejection of pig tissue.

The human body, as well as those of other species, naturally produces antibodies against tissues from other species. One of these antibodies attacks a molecule called alpha-Gal, found on the cells of pigs and most other animals but not on the cells of humans. This has been shown to play a key role in rejection of cross-species organ transplants.

In this study, the TBRC group used a strain of mice in which the gene for their version of alpha-Gal had been knocked out, producing an animal model that duplicated the human situation. The mice received transplants of bone marrow into which a copy of the pig alpha-Gal gene had been inserted using a new gene therapy technique developed by the MGH team. Several weeks later, the mice that received the altered marrow no longer produced antibodies against the pig alpha-Gal molecule, while a control group that had received normal marrow continued to produce the antibodies. Iacomini notes that, while other approaches to inducing tolerance to transplants from other species have produced only temporary results, this new approach may allow the immune system to accept permanently an animal organ without overall immune system suppression.

The paper's co-authors are graduate student Jennifer L. Bracy and David H. Sachs, MD, director of the TBRC.