Xenotransplantation involves the transplantation of nonhuman tissues or organs into human recipients. The concept was pioneered a century ago, when transplanting human organs was considered ethically controversial. Grafts were quickly rejected, however, because of unknown forces later identified as immune responses.
Interest in xenotransplantation reemerged during the 1960s, when large advances were made in immunology. Chimpanzee kidneys have been transplanted into patients with renal failure.[1] In 1984, a baboon heart was transplanted into a newborn infant, Baby Fae, who had hypoplastic left heart syndrome and lived 20 days after heart surgery.[2] A baboon liver was transplanted to a patient with hepatic failure.[3] Porcine islet cells of Langerhans have been injected into patients with type 1 diabetes mellitus.[4] Porcine skin has been grafted onto burn patients,[5] and pig neuronal cells have been transplanted into patients with Parkinson (Parkinson’s) disease and Huntington (Huntington’s) disease.[6]
During these advances, several obstacles to the success of xenotransplantation have been identified. These include, but are not limited to, (1) preventing hyperacute rejection, (2) preventing acute vascular rejection, (3) facilitating immune accommodation, (4) inducing immune tolerance, (5) preventing the transmission of viruses from xenografts into humans, and (6) addressing the ethical issues surrounding animal sources for xenografts and the appropriate selection of recipients (given that xenotransplantation remains experimental). The purpose of this review is to identify the obstacles and recent progress made in the field of xenotransplantation.
The rationale of xenotransplantation
The motivation for using animal sources for organ or tissue transplantation is driven by supply and demand. According to the most current report from the United Network for Organ Sharing (UNOS), more than 107,241 Americans were waiting for organ transplantation as of May 2010.[7] In 2009, 28,464 patients had transplants, and approximately 40% of listed candidates on waiting list were younger than 50 years.
In light of the lack of supply of human organs for transplantation, several alternatives have been investigated and debated. Implantable mechanical devices have been explored in the field of cardiac transplantation. Recently, research has increased in the area of transplanting embryonic cells across species and growing kidneys and endocrine pancreas cells in situ.[8] Organs from pigs have been the focus of much of the research in xenotransplantation, in part because of the public acceptance of killing pigs and the physiologic similarities between pigs and human and nonhuman primates. Xenotransplantation of organs from chimpanzees and baboons has been avoided, however, because of ethical concerns and fear of transmission of deadly viruses (see Biologic Barriers to Xenotransplantation).
Xenografts have been proposed as appropriate for infants who are physically too small to accommodate organs retrieved from adult or pediatric donors. Additionally, organs from animal sources could be transplanted into patients currently excluded from the human organ transplantation list. Finally, most patients perceive xenotransplantation as an acceptable bridge to transplantation of human organs in life-threatening situations.[9]
History of the procedure
Alexis Carrel is known as the founding father of experimental organ transplantation because of his pioneering work with vascular techniques. Carrel and Guthrie contributed substantially to the science of transplantation from 1904-1906. They performed autogenous vein grafts, performed leg replantation in dogs, and developed the famous patch-graft technique for widening narrowed vessels. They also performed heterotopic experimental transplantation. Parts of a small dog were transplanted into the neck of a larger dog. They developed the buttonhole technique for anastomosis of donor and recipient