Xenotransplantation

In a xenotransplantation (Greek ξένος, xenos: stranger ) is the transmission of life and functioning cells or cell clusters (including whole organs or body parts) between different species.

Of these, the allograft is to be distinguished, in which the transfer between genetically different individuals of the same species is performed.

Due to the limited availability of donor organs for allotransplantation, xenotransplantation promises to be a possible alternative. Heart valves from pigs are used today to mechanical as a possible alternative. The heart valves but are processed so that they bear no antigen on the surface that could be recognized as foreign. However, until today there are whole organ xenotransplantation in humans is not possible.

Although primates are much more closely related to humans, pigs are traded today as the most promising option for organ transplants. Pig organs are physiologically more suitable to meet the requirements of the human body. The first cardiac xenotransplantation of a human with a chimpanzee heart showed that the heart was too small to maintain the blood circulation ( Hardy, Mississippi 1964). Pig hearts, however, have a sufficient function of the left ventricle in order to keep a human alive and are also small enough to fit into the thorax.

Mechanisms of rejection

The rejection reaction can be roughly divided into four different time periods:

Hyperacute rejection ( HAR - hyperacute rejection )

The first stage of the rejection reaction occurs within the first 24 hours. Here already formed antibodies directed against the endothelial cells of the implant. Through the addition of these IgG antibodies leads to complement activation, swelling of the endothelium and microvascular thrombosis.

The here for carrying antibodies directed against Galα1, 3Galβ1, 4GlcNAc ( αGal ) carbohydrate side chains of the endothelial cells of the pig. These side chains are located on the endothelial cells of non- primate mammals and New World monkeys and are not present in humans and Old World monkeys. By natural infections of the gastrointestinal tract with αGal -expressing microorganisms of the human body is already very early antibodies to these carbohydrates. To avert this kind of rejection, succeeded in 2002 a so-called co- pig ( αGal - / -) for this carbohydrate to generate, with the next phases of rejection could be achieved.

Acute vascular rejection ( AVR - acute vascular rejection )

This section of the rejection, which occurs within a few days, similar to the HAR, but here cells of the innate immune system are still involved, such as NK cells, macrophages and neutrophils.

Acute humoral xenograft rejection ( AHXR - acute humoral xenograft rejection )

In this phase, new antibodies against the xenograft are formed, which are not directed against αGal. Here, too, both the complement is activated and the blood coagulation system.

Chronic rejection

In the last experimental phase reached xenotransplantation it comes to the development of thrombotic microangiopathy.

Risks and ethical concerns

The biggest concern, the use of xenografts is the risk of transmitting animal pathogens on the host and on the whole of humanity. There are observations that endogenous porcine retroviruses ( PERVs - porcine endogenous retrovirus ) can be transferred to human cell lines. However, there is still no proof that this can happen in vivo. There are ethical concerns in xenotransplantation, since in this case a chimera is formed, containing the living cells of two different species.

From a religious point of view, there are different concerns. At the XVIII International Congress of the Transplantation Society in Rome in 2000, Pope John Paul II has approved the use of pigs as organ donors.

Xenotransplantation of human tissue, such as tumor cells in laboratory animals - especially nude mice - (called xenografts ) is an established method in preclinical research since 1972.