Xenotransplantation: Another Alternative to Embryonic Stem Cell Research
More than one woman has exclaimed, “Men are pigs!” Ongoing biomedical advances may well make this sentiment much more than a metaphorical insult as researchers explore the possibility of using pigs as a source of organs for transplant procedures.
The idea of transplanting organs from animals into humans (xenotransplantation) is not new. But the genuine hope of making this practice a viable medical procedure is. The prospect of xenotransplantation promises to save human lives—not just by providing desperately needed organs for transplant procedures, but by obviating the need for tissue-replacement procedures based on embryonic stem cells.
A perspectives article published in PLoS Medicine summarizes some of the recent scientific breakthroughs. These discoveries have prompted scientists to seriously consider xenotransplantation as a possible means to close the widening gap between the organs required and the organs available for transplant.1
One of the chief hurdles for xenotransplantation from pigs to humans is hyperacute rejection(HAR). When pig organs are transplanted into primates, rejection occurs within minutes due to the presence of a cell surface sugar (α 1,3-galactose). This sugar is present in most mammals, but absent in primates (which includes humans). This cell surface sugar elicits a vigorous immune response by the primate organ recipient.
There are good prospects for overcoming this problem. Researchers have genetically engineered and cloned pigs that lack a functional gene for 1,3-galactosyltransferase, the enzyme that adds α 1,3-galactose to the cell surface. Organs from these genetically engineered pigs are not immediately subjected to HAR when implanted into baboons (a laboratory stand-in for humans), but the organs are eventually rejected. This rejection is caused by antigens that have no relation to α 1,3-galactose.
Still, biomedical researchers have been able to achieve organ survival up to 6 months in baboons when immune suppressants are administered. Unfortunately, the levels of immune suppressants that are required leave the organ recipient unusually susceptible to infection.
The good news is that these and other studies have led to improved understanding of the immune mechanisms responsible for organ rejection. And the new insights suggest ways to disrupt these immune pathways. Exploratory work toward this end is already underway.
Another problem facing xenotransplantation involves increased susceptibility to infection by pathogens that are not normally associated with human diseases. This vulnerability stems from both the compromised state of the immune system (due to the necessary administration of immune suppressants) and the exposure to pig-specific pathogens. Porcine endogenous retroviruses (PERVs) are of particular concern. PERVs are viruses that have been incorporated into pig genetic material. Researchers have shown that in a laboratory setting, PERVs can infect human cells. This raises concerns that PERVs could infect human cells after an organ transplant, unleashing novel diseases among humans. While this concern can’t be minimized, it’s noteworthy that people have been treated with pig tissues for years with no evidence of PERV infections. Also, selective breeding practices could dramatically reduce the number of pathogens associated with the pig organ donors. For example, swine breeds that don’t express human-infectious PERVs have been identified.
All-in-all, excellent progress has been made in pig-to-human xenotransplantation. Clearly, difficulties abound, but the future prospects for xenotransplantation look good. As Muhammad M. Mohiuddin, the author of the PLoS Medicine article notes: “research in this field is progressing in the right direction.”2
The greatest hindrance to xenotransplantation, however, is not scientific, it’s monetary. Currently, limited funding is available to support research efforts in xenotransplantation.
The lack of funding for xenotransplantation is tragic. Pro-life advocates need to speak out in support of xenotransplantation and campaign for increases in federal and state funding for this research program. This procedure serves as another important alternative to embryonic stem cell research (ESCR).
The biomedical community hopes that ESCR will lead to techniques that can generate replacement tissues from embryonic stem cells(ESCs). The claim is that implanting replacement tissue derived from ESCs into damaged and diseased organs provides the means to treat and possibly cure many horrendous diseases and debilitating injuries. Unfortunately, in order to harvest stem cells from human embryos, the embryo must be destroyed.
Use of pig organs for transplant procedures could be used in place of tissue replacement procedures in some instances, particularly in cases of severe organ damage.
One day men (or least parts of them) really may be pigs. And they may be alive, enjoying an improved quality of life because of it—without having to destroy human embryos for their stem cells.
