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XENOTRANSPLANTS: A KEY TO MODERN IMPLANTS
Arin Natania. S
Doctor of Pharmacy, Sri Ramakrishna Institute of Paramedical Sciences, Coimbatore
Bachelor of Engineering (Mech Dept.), CSI College of Engineering, Ketti, Nilgiris
ABSTRACT: Organ transplantation resembles the ultimate treatment possibility of many respiratory, cardiac, hepatic and renal diseases and belongs to the socio-economic most expensive therapeutic pathways of modem medicine. Although transplantation has been routinely established for organs such as the heart, lung, liver and kidney, the therapeutic value of the techALTEX 19, 1/02 nique is still limited by a multitude of factors. Amongst them, the dysfunction of the graft organ is a major complication which depends upon factors such as surgical techniques, preservation procedures, ineffective immune-suppressive therapy and further donor/host characteristics. Apart from the initial focus on surgical techniques, research in transplantation medicine has now become multidisciplinary and many studies are performed by the use of animal models of isolated and perfused organs.
1. Human organ transplantation is a relatively new field of medicine that is now facing a significant challenge. Because of its clinical success, the need for this procedure far exceeds the availability of donor organs. Human organ transplantation faces a significant challenge because the need for this procedure far exceeds the availability of donor organs. Each year fewer than half the people on transplant waiting lists receive organ transplants. Approximately 10 people die each day waiting for organs to become available. Even if all potential donors elect to donate, the supply of human organ donations will continue to fall short of the need.
2. One solution doctors along with pharmaceutical and biotechnology companies are investigating to end this acute shortage is "xenotransplantation," or the process of transplanting cells, tissues or organs from one species to another.
3. Rejection, in which the recipient’s body attacks the new organ like an infection, is the greatest practical obstacle to xenotransplantation. The breeding of transgenic pigs as well as new cloning techniques may be used to reduce the risk of organ rejection. The demand for organ transplantation will continue to increase as improved technical skills and anti-rejection medication make transplant a realistic option for groups of people previously considered too vulnerable for example, those with diabetes. Also, many other people may benefit from transplantation of cells or tissues to treat countless other diseases such as diabetes, Parkinson’s, Huntington’s, cancer, and injuries to the spinal cord or other organs and limbs.
One solution doctors along with pharmaceutical and biotechnology companies are investigating to end this acute shortage is "xenotransplantation," or the process of transplanting cells, tissues or organs from one species to another. While still in the experimental stages, xenotransplantation is a potentially life-saving option for people with such ailments as severe heart disease and kidney failure. Preliminary data from experiments using transplanted pig cells in patients with diabetes and Parkinson’s disease are encouraging.
HISTORY OF XENOTRANSPLANTATION
The first experiments in transplanting chimpanzee kidneys into humans were conducted in 1963 and 1964. One of the patients who received chimpanzee kidneys lived for nine months.
Two of the most publicized xenotransplant operations in the last two decades involved Baby Fae, the infant who received a baboon heart in 1984, and Jeff Getty, an AIDS patient who received a bone marrow transplant from a baboon in 1995. Baby Fae lived with her xenotransplant for 20 days, while Getty rejected the transplanted marrow almost immediately. As of October 1998, Getty remained free of baboon-transmitted viruses and showed no signs of baboon bone marrow in his system.
Researchers are currently experimenting with pigs as sources of organs and tissues for xenotransplantation. Studies include the use of pancreatic islet cells and neural cells from pigs for insulin-dependent diabetes and refractory parkinsonism, as well as perfusion of a patient’s fluids through a pig liver situated outside the patient’s body as a temporary strategy to treat liver failure. Patients with Huntington’s disease, which is a neurodegenerative condition characterized by uncontrolled movement and mental deterioration, also are receiving modified tissues from pigs as an experimental treatment. These studies are still very preliminary in testing the safety and effectiveness of this promising treatment.
APPROPRIATE ANIMALS FOR USE IN XENOTRANSPLANTATION
Scientists advise that domesticated animals such as pigs and cows be considered as potential tissue and organ sources before nonhuman primates, such as monkeys, for a number of health, safety and logistical reasons. Pigs are preferred because they mature very quickly, produce large litters and have organs of comparable size and function to human organs in both infancy and adulthood. They also can be bred to high health standards in microbiologically controlled environments.
Monkeys, on the other hand, are undomesticated animals that do not fare well in controlled environments and, therefore, it is difficult to raise them to the same high health standards as pigs. Furthermore, their organs are much too small and, like humans, monkeys mature slowly and tend to give birth to one offspring at a time. Although humans might reject nonhuman primate organs less frequently and vigorously than those of other species because of their genetic similarities, these similarities could facilitate disease spread between the donor and recipient.
ADDRESSING ORGAN REJECTION
Rejection, in which the recipient’s body attacks the new organ like an infection, is the greatest practical obstacle to xenotransplantation. Traditionally in transplants of organs from one human to another, drug therapies, such as cyclosporine, are used to suppress recipients’ immune systems in order to allow transplanted organs to function without being attacked and rejected as foreign. In xenotransplantation, a more aggressive defense mechanism called "hyperacute rejection" occurs when tissue not recognized as human is introduced to the body. In a matter of minutes, an individual’s immune system sets out to destroy the transplanted organ.
One technology being developed to overcome such organ rejection is the breeding of transgenic pigs. These genetically-altered pigs express specific human proteins that make it more difficult for the human immune system to identify the porcine organ as belonging to a different species. A transgenic pig is bred by injecting a small amount of DNA (or genetic material) mimicking a human gene sequence into a fertilized pig egg and then implanting that egg into a sow leading to the pig’s birth.
New cloning techniques may further enhance the immunocompatibility of pig organs by eliminating the pig gene-products that cause hyperacute rejection. In theory these developments should mean that once transplanted, animal organs could be treated in the same way as human organs, with the use of standard immunosuppressive regimens.
ADDRESSING POTENTIAL RISK OF INFECTION
Xenotransplantation opponents voice concerns regarding the unpredictable nature of microorganisms. They point to existing human viruses suspected to have originated in animals -- human immunodeficiency virus, simian immunodeficiency virus and bovine spongiform encephalopathy (BSE), in which people developed Creutzfeldt-Jakob Disease, the human equivalent to BSE. They express concern that xenotransplantation puts society as well as the individual recipient at risk for disease. If PoERV’s are found to pose a risk, strategies are being developed that may provide a solution to the problem.
U.S. AND INTERNATIONAL REGULATION OF XENOTRANSPLANTATION
While governments of the United States, the United Kingdom, Spain and elsewhere share similar hopes and concerns regarding xenotransplantation, each is working independently to establish or revise guidelines regarding the regulation of xenotransplantation research. In the U.S., the Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research published its guidelines in 1999. The guidelines, shaped in part by public dialogue, include long-term monitoring of recipients and the establishment of a registry to archive patient records and donor samples. The various agencies of the U.S. Department of Health and Human Services, including the FDA, the Centers for Disease Control and Prevention and the National Institutes of Health, have encouraged open communication about xenotransplantation at public workshops for several years.
In the United States, several scientists who attended the public conference in January 1998, "Developing U.S. Public Health Policy on Xenotransplantation," urged the FDA to ban cross-species transplantation research until ethical issues and health risks are resolved. They specifically discussed the potential risk to public health from a viral transfer across species that could result in a new disease epidemic. The FDA decided it was appropriate to allow well-defined and highly controlled clinical trials, which are proceeding at a cautious pace.
In UK, Spain and other countries clinical trials are being conducted whereas in few countries the trials and practice are banned.
ETHICAL ISSUES SURROUNDING XENOTRANSPLANTATION
In addition to the critically important potential public health issues in xenotransplantation, there are a number of ethical issues that should be addressed. These include: deciding upon the fairest way to allocate donor animal organs in a society where thousands of people die while waiting for a transplant; deciding whether or not persons who receive xenografts may be compelled to participate in long term follow-up programs because of the theoretical public health risk from endogenous viruses; It would be naive to think that all these and other ethical issues will be resolved in advance of the technological readiness to attempt animal to human xenografts. However, it is crucial that those in the biotechnology industry who are working in this area help to initiate and sustain an ongoing public dialogue on these and related issues.
A number of independent bodies across the world have considered the ethics of xenotransplantation and found it to be ethically acceptable. While we believe that xenotransplantation could be the answer for thousands of patients who will require transplants of tissues or solid organs, the industry and the scientific community must proceed with caution to ensure the safe development of this potentially life-saving technology.
2. Ekser B, Li P, Cooper DKC. Xenotransplantation: past, present, and future. Curr Opin Organ Transplant. 2017;22(6):513-521. doi:10.1097/MOT.0000000000000463