Xenotransplantation (xeno- from the Greek Greek , an independent branch of the Indo-European family of languages, is the language of the Greeks. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. In its ancient form, it is the language of classical ancient Greek literature and the New Testament of meaning "foreign") is the transplantation Organ transplantation is the moving of an organ from one body to another, or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of Regenerative medicine is allowing scientists and engineers to create organs to be re-grown from the patient's own cells Organs and/or of living cells The cell is the functional basic unit of life. It was discovered by Robert Hooke and is the functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. Some organisms, such as most bacteria, are unicellular . Other organisms, such as humans,, tissues Tissue is a cellular organizational level intermediate between cells and a complete organism. Hence, a tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. Organs are then formed by the functional grouping together of multiple tissues or organs In biology and anatomy, an organ is a collection of tissues joined in structural unit to serve a common function from one species In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are often used, such as based on similarity of DNA or to another, such as from pigs to humans (see medical grafting In medicine, the word grafting can refer to a surgical procedure to transplant tissue. The implanted tissue must have a blood supply, either surgically created by anastomosis of blood vessels or by growth of blood vessels from the new vascular bed. The word grafting can also refer to the placement of a natural or artificial conduit to carry blood)[1]. Such cells, tissues or organs are called xenografts or xenotransplants. In contrast, the term allotransplantation Allotransplantation is the transplantation of cells, tissues, or organs, sourced from a genetically non-identical member of the same species as the recipient.. The transplant is called an allograft or allogeneic transplant or homograft. Most human tissue and organ transplants are allografts refers to a same-species transplant. Human xenotransplantation offers a potential treatment for end-stage organ failure, a significant health problem in parts of the industrialized world. It also raises many novel medical, legal and ethical issues.[2] A continuing concern is that pigs have shorter lifespans than humans: their tissues age at a different rate. Disease transmission (xenozoonosis) and permanent alteration to the genetic code of animals are also causes for concern. There are few published cases of successful xenotransplantation.[3]

Contents

Potential future uses

Because there is a worldwide shortage of organs for clinical implantation, about 60% of patients awaiting replacement organs die on the waiting list.[citation needed] Recent advances in understanding the mechanisms of transplant rejection have brought science to a stage where it is reasonable to consider that organs from other species, probably pigs, may soon be engineered to minimize the risk of serious rejection and used as an alternative to human tissues, possibly ending organ shortages. Other procedures, some of which are being investigated in early clinical trials, aim to use cells or tissues from other species to treat life-threatening and debilitating illnesses such as cancer Cancer /ˈkænsər/ (medical term: malignant neoplasm) is a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties, diabetes Diabetes mellitus, often simply referred to as diabetes—is a condition in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood sugar produces the classical symptoms of polyuria , polydipsia (increased thirst) and polyphagia (, liver failure Liver failure is the inability of the liver to perform its normal synthetic and metabolic function as part of normal physiology. Two forms are recognised: and Parkinson's disease Parkinson's disease is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills, speech, and other functions. If vitrification Cryopreservation is a process where cells or whole tissues are preserved by cooling to low sub-zero temperatures, such as 77 K or −196 °C (the boiling point of liquid nitrogen). At these low temperatures, any biological activity, including the biochemical reactions that would lead to cell death, is effectively stopped. However, when can be perfected, it could allow for long-term storage of xenogenic cells, tissues and organs In biology and anatomy, an organ is a collection of tissues joined in structural unit to serve a common function so that they would be more readily available for transplant.

Xenotransplants could save thousands of patients waiting for donated organs. The animal organ, probably from a pig or baboon could be genetically altered with human genes to trick a patient’s immune system into accepting it as a part of its own body. They have re-emerged because of the lack of organs available and the constant battle to keep immune systems from rejecting allotransplants. Xenotransplants are thus potentially a more effective alternative.

Also, xenotransplantation of ovarian tissue into immunodeficient nude mice or SCID mice is already used in research to study the development of ovarian follicles.[4] Mature follicles have developed, even after use of cryopreserved ovarian tissue.[5] Both host and graft vessels contribute to the revascularization Revascularization is "a surgical procedure for the provision of a new, additional, or augmented blood supply to a body part or organ." The term derives from the prefix re-, in this case meaning "restoration" and vasculature, which refers to the circulatory structures of an organ.[citation needed] of xenografted human ovarian tissue in a mice.[6]

Potential future animal organ donors

Since they are the closest relatives to humans, nonhuman primates were first considered as a potential organ source for xenotransplantation to humans. Chimpanzees were originally considered to be the best option since their organs are of similar size, and they have good blood type compatibility with humans. However, since chimpanzees are listed as an endangered species, other potential donors were sought out. Baboons are more readily available, however they are also not practical as potential donors. Problems include their smaller body size, the infrequency of blood group O (the universal donor), their long gestation period, and they typically produce few offspring. In addition, a major problem with the use of nonhuman primates is the increased risk of disease transmission, since they are so closely related to humans.[7] Pigs are currently thought to be the best candidates for organ donation. The risk of cross-species disease transmission is decreased because of their increased phylogenetic distance from humans .[8] They are readily available, their organs are anatomically comparable in size, and new infectious agents are less likely since they have been in close contact with humans through domestication for many generations .[9]. Current experiments in xenotransplantation most often use pigs as the donor, and baboons as human models.

Barriers and issues

Immunologic Barriers

To date no xenotransplantation trials have been entirely successful due to the many obstacles arising from the response of the recipient’s immune system An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own healthy cells and tissues in order to function. This response, which is generally more extreme than in allotransplantations, ultimately results in rejection of the xenograft. There are several types of rejection organ xenografts are faced with, these include:

A rapid, violent hyperacute response results due to preformed natural antibodies Antibodies are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses. They are typically made of basic structural units—each with two large heavy chains and two small light chains—to form, for example,, known as XNAs.[10]

Hyperacute Rejection

This rapid and violent type of rejection occurs within minutes to hours from the time of the transplant. It is mediated by the binding of XNAs (xenoreactive natural antibodies) to the donor endothelium, causing activation of the human complement system The complement system is a biochemical cascade that helps, or “complements”, the ability of antibodies to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime. However, it can be recruited and brought into action which results in endothelial damage, inflammation, thrombosis and necrosis of the transplant. XNAs are first produced and begin circulating in the blood in neonates, after colonization of the bowel by bacteria which have galactose moieties on their cell walls. Most of these antibodies are the IgM Immunoglobulin M, or IgM for short, is a basic antibody that is present on B cells. It is the primary antibody against A and B antigens on red blood cells. IgM is by far the physically largest antibody in the human circulatory system. It is produced after an animal has been exposed to an antigen for an extended time or when an animal is exposed to class, but also include IgG Immunoglobulin G is a monomeric immunoglobulin, built of two heavy chains γ and two light chains. Each IgG has two antigen binding sites. It is the most abundant immunoglobulin and is approximately equally distributed in blood and in tissue liquids, constituting 75% of serum immunoglobulins in humans. IgG molecules are synthesized and secreted by, and IgA Immunoglobulin A is an antibody that plays a critical role in mucosal immunity. More IgA is produced in mucosal linings than all other types of antibody combined; between 3 and 5g is secreted into the intestinal lumen each day. IgA has two subclasses (IgA1 and IgA2) and can exist in a dimeric form called secretory IgA (sIgA). In its secretory form,. .[9].

The epitope XNAs target is an α-linked galactose moiety, Gal-α-1,3Gal (also called the α-Gal epitope), produced by the enzyme α-galactosyl transferase.[11]. Most non-primates contain this enzyme thus, this epitope is present on the organ epithelium and is perceived as a foreign antigen An antigen is a molecule recognized by the immune system. Originally the term came from antibody generator and was a molecule that binds specifically to an antibody, but the term now also refers to any molecule or molecular fragment that can be bound by a major histocompatibility complex and presented to a T-cell receptor. "Self" by primates, which lack the galactosyl transferase enzyme. In pig to primate xenotransplantation, XNAs recognize porcine glycoproteins of the integrin family .[9].

The binding of XNAs initiate complement activation through the classical complement pathway The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. Complement activation causes a cascade of events leading to: destruction of endothelial cells, platlet degranulation, inflammation, coagulation, fibrin deposition, and hemorrhage. The end result is thrombosis Thrombosis is the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss. If the clotting is too severe and the clot breaks free, the traveling clot is now know as an and necrosis Necrosis is the premature death of cells and living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death. While apoptosis often provides beneficial effects to the organism, necrosis is almost always of the xenograft .[9].

Overcoming Hyperacute rejection

Since hyperacute rejection presents such a barrier to the success of xenografts several strategies to overcome it are under investigation:

Interruption of the complement cascade • The recipient's complement cascade can be inhibited through the use of cobra venom factor (which depletes C3), soluble complement receptor type 1, anti-C5 antibodies, or C1 inhibitor (C1-INH). Disadvantages of this approach include the toxicity of cobra venom factor, and most importantly these treatments would deprive the individual of a functional complement system .[8]

Transgeneic organs (Genetically engineered pigs) •1,3 galactosyl transferase gene knockouts - These pigs don’t contain the gene which codes for the enzyme responsible for expression of the immunogeneic gal-α-1,3Gal moiety (the α-Gal epitope) [12]. •Increased expression of H-transferase (α 1,2 fucosyltransferase), an enzyme that competes with galactosyl transferase. Experiments have shown this reduces α-Gal expression by 70% [13]. •Expression of human complement regulators (CD55, CD46, and CD59) to inhibit the complement cascade [14].

•Plasmaphoresis, on humans to remove 1,3 galactosyltransferase, reduces the risk of activation of effector cells such as CTL (CD8 T cells), complement pathway activation and delayed type hypersensitivity (DTH).

Acute Vascular Rejection

Also known as delayed xenoactive rejection, this type of rejection occurs in discordant xenografts within 2 to 3 days, if hyperacute rejection is prevented. The process is much more complex than hyperacute rejection and is currently not completely understood. Acute vascular rejection requires de novo protein synthesis and is driven by interactions between the graft endothelial cells and host antibodies, macrophages, and platelets. The response is characterized by an inflammatory infiltrate of mostly macrophages Macrophages are white blood cells within tissues, produced by the differentiation of monocytes. Human macrophages are about 21 micrometres (0.00083 in) in diameter. Monocytes and macrophages are phagocytes, acting in both non-specific defense (innate immunity) as well as to help initiate specific defense mechanisms (adaptive immunity) of and natural killer cells Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses. The cells kill by releasing small cytoplasmic granules of proteins called perforin and granzyme that cause the target cell to die by apoptosis or (with small numbers of T cells T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and natural killer cells by the presence of a special receptor on their cell surface called T cell receptors (TCR). The abbreviation T, in T), intravascular thrombosis, and fibrinoid necrosis of vessel walls [11]. Binding of the previously mentioned XNAs to the donor endothelium leads to the activation of host macrophages as well as the endothelium itself. The endothelium activation is considered type II since gene induction and protein synthesis are involved. The binding of XNAs ultimately leads to the development of a procoagulant state, the secretion of inflammatory cytokines Cytokines are any of a number of small proteins that are secreted by specific cells of the immune system and glial cells, which carry signals locally between cells, and thus have an effect on other cells. They are a category of signaling molecules that are used extensively in cellular communication. They are proteins, peptides, or glycoproteins and chemokines Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines. Proteins are classified as chemokines according to shared structural characteristics such as small size (they are all approximately 8-10, as well as expression of leukocyte adhesion molecules such as E-selectin E-selectin, also known as CD62E, is a cell adhesion molecule expressed only on endothelial cells activated by cytokines. Like other selectins, it plays an important part in inflammation. In humans, E-selectin is encoded by the SELE gene, intercellular adhesion molecule-1 (ICAM-1 ICAM-1 also known as CD54 (Cluster of Differentiation 54) is a human gene), and vascular cell adhesion molecule-1 (VCAM-1) .[9]. This response is further perpetuated as normally binding between regulatory proteins and their ligands aid in the control of coagulation and inflammatory responses. However, due to molecular incompatibilities between the molecules of the donor species and recipient (such as porcine major histocompatibility complex The major histocompatibility complex is a large genomic region or gene family found in most vertebrates. It is the most gene-dense region of the mammalian genome and plays an important role in the immune system and autoimmunity. The diversity of MHC is important in the immune diversity in the population. The proteins encoded by the MHC are molecules and human natural killer cells), this may not occur [11].

Overcoming Acute Vascular Rejection

Due to its complexity, with the use of immunosuppressive drugs along with a wide array of approaches are necessary to prevent acute vascular rejection, and include: • Administering a synthetic thrombin inhibitor to modulate thrombogenesis • Depletion of anti-galactose antibodies (XNAs) by techniques such as immunoadsorption, to prevent endothelial cell activation • Inhibiting activation of macrophages (stimulated by CD4+ T cells) and NK cells (stimulated by the release of Il-2). Thus, the role of MHC molecules and T cell responses in activation would have to be reassessed for each species combo [11].

Accommodation

If hyperacute and acute vascular rejection are avoided accommodation is possible, which is the survival of the xenograft despite the presence of circulating XNAs. The graft is given a break from humoral rejection [15] when the complement cascade is interrupted, circulating antibodies are removed, or their function is changed, or there is a change in the expression of surface antigens on the graft. This allows the xenograft to up-regulate and express protective genes, which aid in resistance to injury, such as heme oxygenase-1 (an enzyme that catalyzes the degradation of heme) .[9].

Cellular rejection

Rejection of the xenograft in hyperactute and acute vascular rejection is due to the response of the humoral immune system, since the response is elicited by the XNAs. Cellular rejection is based on cellular immunity, and is mediated by: 1. Natural killer cells, which accumulate in and damage the xenograft; and 2. T-lymphocytes - which are activated by MHC molecules through both direct and indirect xenorecognition.

In direct xenorecognition, antigen presenting cells from the xenograft present peptides to recipient CD4+ T cells via xenogeneic MHC class II molecules, resulting in the production of interleukin 2 Interleukin-2 is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign (non-self) and self. IL-2 mediates its effects by binding to IL-2 receptors, which are expressed by lymphocytes, (IL-2). Indirect xenorecognition involves the presentation of antigens from the xenograft by recipient antigen presenting cells to CD4+ T cells. Antigens of phagocytosed graft cells can also be presented by the host’s class I MHC molecules to CD8+ T cells.[8][16]. The strength of cellular rejection in xenografts remains uncertain, however it is expected to be stronger than in allografts due to differences in peptides among different animals. This leads to more antigens potentially recognized as foreign, thus eliciting a greater indirect xenogenic response .[8]

Overcoming Cellular rejection

A proposed strategy to avoid cellular rejection is to induce donor non-responsiveness using haematopoietic chimerism. Donor stem cells are introduced into the bone marrow of the recipient, where they coexist with the recipient’s stem cells. The bone marrow stem cells give rise to cells of all haematopoietic lineages, through the process of hematopoiesis Haematopoiesis (or hematopoiesis in the United States; sometimes also haemopoiesis or hemopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult person, approximately 1011–1012 new blood cells are produced daily in order to maintain steady state levels. Lymphoid progenitor cells are created by this process and move to the thymus where negative selection eliminates T cells found to be reactive to self. The existence of donor stem cells in the recipient’s bone marrow causes donor reactive T cells to be considered self and undergo apoptosis Apoptosis is the process of programmed cell death (PCD) that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, loss of cell membrane asymmetry and attachment, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA .[8]

Chronic rejection

This final type of rejection is slow and progressive, and is usually described in transplants which survive the initial rejection phases. Scientists are still unclear how chronic rejection exactly works, research in this area is difficult since xenografts rarely survive past the initial acute rejection phases. Nonetheless, it is known is that XNAs and the complement system are not primarily involved [11]. Fibrosis Fibrosis is the formation or development of excess fibrous connective tissue in an organ or tissue as a reparative or reactive process, as opposed to a formation of fibrous tissue as a normal constituent of an organ or tissue. Scarring is confluent fibrosis that obliterates the architecture of the underlying organ or tissue in the xenograft occurs as a result of immune reactions, cytokines (which stimulate fibroblasts), or healing (following cellular necrosis in acute rejection). Perhaps the major cause of chronic rejection is arteriosclerosis It should not be confused with "arteriolosclerosis" or "atherosclerosis", which are described in greater detail below. Lymphocytes, which were previously activated by antigens in the vessel wall of the graft, activate macrophages to secrete smooth muscle growth factors. This results in a build up of smooth muscle cells on the vessel walls, causing the hardening and narrowing of vessels within the graft. Chronic rejection leads to pathologic changes of the organ, and is why transplants must be replaced after so many years ([16]. It is also anticipated that chronic rejection will be more aggressive in xenotransplants as opposed to allotransplants [17].

Physiology

Extensive research is required to determine whether animal organs can replace the physiological functions of human organs. Many issues include:

• Size - Differences in organ size limit the range of potential recipients of xenotransplants. • Longevity - The lifespan of most pigs is roughly 15 years, currently it is unknown whether or not a xenograft may be able to last longer than that. • Hormone and protein differences - Some proteins will be molecularly incompatible, which could cause malfunction of important regulatory processes. These differences also make the prospect of hepatic xenotransplantation less promising, since the liver plays an important role in the production of so many proteins .[8] • Environment - For example, pig hearts work in a different anatomical site and under different hydrostatic pressure than in humans [11]. • Temperature - The body temperature of pigs is 39°C (2°C above the average human body temperature). Implications of this difference, if any, on the activity of important enzymes are currently unknown. .[8]

Xenozoonosis

Xenozoonosis, also known as zoonosis A zoonosis or zoonose is any infectious disease that can be transmitted (in some instances, by a vector) from non-human animals, both wild and domestic, to humans or from humans to non-human animals (the latter is sometimes called reverse zoonosis). Many serious diseases fall under this category or xenosis, is the transmission of infectious agents between species via a xenograft. Animal to human infection is normally rare, but has occurred in the past. An example of such is the avian influenza Avian influenza, sometimes avian flu, and commonly bird flu, refers to "influenza caused by viruses adapted to birds."[clarification needed] Of the greatest concern is highly pathogenic avian influenza, when an influenza A virus was passed from birds to humans [18]. Xenotransplantation may increase the chance of disease transmission for 3 reasons: 1. Implantation breaches the physical barrier that normally helps to prevent disease transmission, 2. The recipient of the transplant will be severely immunosuppressed; and 3. Human complement regulators (CD46, CD55, and CD59) expressed in transgenic pigs have been shown to serve as virus receptors, and may also help to protect viruses from attack by the compliment system [19].

Examples of viruses carried by pigs include porcine herpesvirus The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein , referring to the latent, recurring infections typical of this group of viruses. Herpesviridae can cause latent or lytic infections, rotavirus Rotavirus is the most common cause of severe diarrhoea among infants and young children, and is one of several viruses that cause infections often called stomach flu, despite having no relation to influenza. It is a genus of double-stranded RNA virus in the family Reoviridae. By the age of five, nearly every child in the world has been infected, parvovirus, and circovirus. Porcine herpesviruses and rotaviruses can be eliminated from the donor pool by screening, however others (such as parvovirus and circovirus) may contaminate food and footwear then re-infect the herd. Thus, pigs to be used as organ donors will have to be housed under strict regulations and screened regularly for microbes and pathogens. Unknown viruses, as well as those which aren’t harmful in the animal, may also pose risks (Takeuchi and George, 2000). Of particular concern are PERVS (porcine endogenous retroviruses), vertically transmitted microbes which are imbedded in swine genomes. The risks with xenosis are twofold as not only could the individual become infected, but a novel infection could initiate an epidemic in the human population. Because of this risk, the FDA has suggested any recipients of xenotransplants shall be closely monitored for the remainder of their life, and quarantined if they show signs of xenosis [20].

Baboons and pigs carry myriad transmittable agents which are harmless in their natural host, but extremely toxic and deadly in humans. HIV is an example of a disease which is believed to have jumped from monkeys to humans. Researchers also do not know if an outbreak of infectious diseases could occur and if they could contain the outbreak even though they have measures for control. Another obstacle facing xenotransplants is that of the body’s rejection of foreign objects by its immune system. These antigens (foreign objects) are often treated with powerful immunosuppressive drugs which could in turn make the patient vulnerable to other infections and actually aid the disease trying to be cured. This is the reason the organs would have to be altered to fit with the patients DNA (histocompatibility Histocompatibility is the property of having the same, or mostly the same, alleles of a set of genes called the major histocompatibility complex. These genes are expressed in most tissues as antigens, to which the immune system makes antibodies. The immune system at first makes antibodies to all sorts of antigens, including those it has never been).

In 2005, the Australian For at least 40,000 years before European settlement in the late 18th century, Australia was inhabited by indigenous Australians, who belonged to one or more of the roughly 250 language groups. After sporadic visits by fishermen from the immediate north and discovery by Dutch explorers in 1606, Australia's eastern half was claimed by the British National Health and Medical Research Council The National Health and Medical Research Council is Australia's peak funding body for medical research, with a budget of nearly A$1bn a year[citation needed]. The Council was established to develop and maintain health standards and is responsible for implementing the National Health and Medical Research Council Act 1992 declared a eighteen-year moratorium on all animal-to-human transplantation, concluding that the risks of transmission of animal viruses to patients and the wider community have not yet been resolved.[21]

Porcine endogenous retroviruses

Endogenous retroviruses Endogenous retroviruses are retroviruses derived from ancient viral infections of germ cells in humans, mammals and other vertebrates; as such their proviruses are passed on to the next generation and now remain in the genome. Retroviruses are viruses that reverse-transcribe their RNA into DNA for integration into the host's genome. Most are remnants of ancient viral infections, found in the genomes of most, if not all, mammalian species. Integrated into the chromosomal DNA, they are vertically transferred through inheritance [17]. Due to the many deletions and mutations they accumulate over time, they usually are not infectious in the host species, however the virus may become infectious in another species .[9]. PERVS were originally discovered as retrovirus particles released from cultured porcine kidney cells [22]. Most breeds of swine harbor approximately 50 PERV genomes in their DNA [23]. Although it is likely that most of these are defective, some may be able to produce infectious viruses so every proviral genome must be sequenced to identify which ones pose a threat. In addition, through complementation and genetic recombination, two defective PERV genomes could give rise to an infectious virus [24]:. There are three subgroups of infectious PERVs (PERV-A, PERV-B, and PERV-C). Experiments have shown that PERV-A and PERV-B can infect human cells in culture [23][25]. To date no experimental xenotransplantations have demonstrated PERV transmission, yet this does not mean PERV infections in humans are impossible [19].

Ethicality

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Xenografts have been a controversial procedure since they were first attempted. Many, including animal rights groups, strongly oppose killing animals in order to harvest their organs for human use.[26] Religious beliefs, such as the Jewish The Jews , also known as the Jewish people, are a nation and ethnoreligious group originating in the Israelites or Hebrews of the Ancient Near East. The Jewish ethnicity, nationality, and religion are strongly interrelated, as Judaism is the traditional faith of the Jewish nation. Converts to Judaism, whose status as Jews within the Jewish ethnos and Muslim A Muslim or Moslem is an adherent of the religion of Islam. Literally, the word means "one who submits (to God)". Muslim is the participle of the same verb of which Islam is the infinitive. All Muslims observe Sunnah, but differences in the definition of what is and what is not Sunnah has led to the emergence of sectarian movements.[ prohibition against eating pork, have been sometimes thought to be a problem, however according to a Council of Europe documentation both religions agree that this rule is overridden by the preservation of human life. In general, the use of pig and cow tissue in humans has been met with little resistance, save some religious beliefs.

Some ethical issues include informed consent complexities for research subjects, as well as the selection of human subjects, rights of patients and medical staff and public education (as many companies may go ahead with experiments without public awareness) [27].

See also

References

  1. ^ See also Definition of the World Health Organization
  2. ^ Many of these are spelled out in Jack M. Kress, "Xenotransplantation: Ethics and Economics," 53 Food and Drug Law Journal 208 (1998).
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  4. ^ Bols PE, Aerts JM, Langbeen A, Goovaerts IG, Leroy JL (April 2010). "Xenotransplantation in immunodeficient mice to study ovarian follicular development in domestic animals". Theriogenology 73 (6): 740–7. doi:10.1016/j.theriogenology.2009.10.002. PMID 19913288.
  5. ^ Lan C, Xiao W, Xiao-Hui D, Chun-Yan H, Hong-Ling Y (December 2008). "Tissue culture before transplantation of frozen-thawed human fetal ovarian tissue into immunodeficient mice". Fertil. Steril.. doi:10.1016/j.fertnstert.2008.10.020. PMID 19108826.
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  23. ^ a b Patience, C., Takeuchi, Y., Weiss, R. 1997. Infection of human cells by an endogenous retrovirus of pigs. Nat Med; 3: 282–286.
  24. ^ Rogel-Gaillard, C., Bourgeaux, N., Billault, A., Vaiman, M., Chardon, P. 1999. Construction of a swine BAC library: application to the characterization and mapping of porcine type C endoviral elements. Cytogenet Cell Genet; 85: 205–211.
  25. ^ Takeuchi, Y., Patience, C., Magre, S., Weiss, R., Banerjee, P., Le Tissier, P., Stoye, J. 1998. Host range and interference studies of three classes of pig endogenous retrovirus. J Virol; 72: 9986–9991
  26. ^ PETA Media Center: Factsheet: Xenotransplantation[4]
  27. ^ Vanderpool, H. 1999. Xenotransplantation: progress and promise. Student BMJ; 12: 422. [5]

Further reading

External links

Look up xenotransplantation in Wiktionary, the free dictionary.
Organ transplantation
Types Autotransplantation · Allotransplantation · Xenotransplantation
Organs and tissues Bone · Bone marrow · Corneal · Face · Hand · Head · Heart · Heart-lung · Kidney · Liver · Lung · Pancreas · Penis · Skin · Spleen · Uterus
Related topics Biomedical tissue · Edmonton protocol · Eye bank · Graft-versus-host disease · Immunosuppressive drugs · Islet cell transplantation · Living donor liver transplantation · Lung allocation score · Machine perfusion · Medical grafting · Non-heart beating donation · Organ donation · Organ harvesting · Organ trade · Post-transplant lymphoproliferative disorder · Total body irradiation · Transplant rejection · Transplantation medicine
Organizations Halachic Organ Donor Society · Human Tissue Authority · National Marrow Donor Program · United Network for Organ Sharing · DKMS Americas
Countries Organ transplantation in the People's Republic of China · Organ transplantation in Israel · Organ transplantation in Japan · Organ theft in Kosovo · Organ transplantation in different countries · Gurgaon kidney scandal
People Christiaan Barnard · Michael Woodruff · Alexis Carrel · Norman Shumway · Jean-Michel Dubernard · List of notable organ transplant donors and recipients

Categories: Transplantation medicine | Immunology | Medical ethics | Surgery | Animal testing

 

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'Xenotransplantation' News
Reportlinker Adds Cell and Stem Cell Therapies for Diabetes - PR Newswire (press release)
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Reportlinker Adds Cell and Stem Cell Therapies for Diabetes

PR Newswire (press release)

Also, porcine islet cells are used for xenotransplantation in only two products. Surprisingly, this is a very young pipeline with 14 out of 19 products ...



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Brown University Providence Rhode Island 02912 Advisor Micheal J Lysaght Ph D Authors Larry Hou Irene Klein Billy Lau Vanessa Rothholtz Yvette Wild May 1999 Dopamine production is highlighted in red in the brain scan of a patient with Parkinson s disease Scan 1 is before fetal tissue transplantation Scan 2 3 show increased dopamine

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Schweine als Organspender: Xenotransplantation bald moeglich?
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Schweine als Organspender: Xenotransplantation bald moeglich?

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hu, 21 Jan 2010 23:20:54 GM

Schweine als Organspender: . Xenotransplanta​tion. bald moeglich? In zwei Jahren will Herzspezialist Bruno Reichart zum ersten Mal auf der Welt einem Menschen ein tierisches Spenderherz einpflanzen. Die groesste Herausforderung​ fuer eine ...

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'Xenotransplantation' Answers
What are the ethics of xenotransplantation?
Q. Why is it an issue? Is the taking of one life justified by the saving of another? Can we play God?
Asked by Beef C - Mon Jun 9 03:08:39 2008 - - 4 Answers - 0 Comments

A. I guess the same people who are opposed to raising and killing an animal to eat it will be opposed to raising and killing an animal to provide an organ. Actually, maybe not - because some vegetarians don't eat meat for ethical reasons, but do so under the assumption that "we don't need meat to survive" (which is true, but it's soo tasty). I wonder whether some of them would not oppose to xenotransplantation since the patients do actually need that organ to survive.
Answered by Lame Name Dame - Submarine - Mon Jun 9 04:23:56 2008

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