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Transplant Engineering
Transplant engineering (or allograft engineering) is a variant of genetic organ engineering which comprises allograft, autograft and xenograft engineering. In allograft engineering the graft is substantially modified by altering its genetic composition. The genetic modification can be permanent or transient. The aim of modifying the allograft is usually the mitigation of immunological graft rejection. History Transient genetic allograft engineering has been pioneered by Shaf Keshavjee and Marcelo Cypel at University Health Network in Toronto by adenoviral transduction for transgenic expression of the IL-10 gene. Permanent genetic allograft engineering has first been done by Rainer Blasczyk and Constanca Figueiredo at Hannover Medical School in Hanover by lentiviral ''Lentivirus'' is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in humans and other mammalian species. The genus includes the human immunodeficiency vir ...
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Genetic Engineering
Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by artificially synthesising the DNA. A construct is usually created and used to insert this DNA into the host organism. The first recombinant DNA molecule was made by Paul Berg in 1972 by combining DNA from the monkey virus SV40 with the lambda virus. As well as inserting genes, the process can be used to remove, or "knock out", genes. The new DNA can be inserted randomly, or targeted to a specific part of the genome. An organism that is generated through genetic engineering is considered to be genetically modified (GM) an ...
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Allograft
Allotransplant (''allo-'' meaning "other" in Greek) is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, or homograft. Most human tissue and organ transplants are allografts. It is contrasted with autotransplantation (from one part of the body to another in the same person), syngenic transplantation of isografts (grafts transplanted between two genetically identical individuals) and xenotransplantation (from other species). Allografts can be referred to as "homostatic" if they are biologically inert when transplanted, such as bone and cartilage. An immune response against an allograft or xenograft is termed rejection. An allogenic bone marrow transplant can result in an immune attack on the recipient, called graft-versus-host disease. Procedure Material is obtained from a donor who is a living person, or a deceased person's body receiving ...
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Autotransplantation
Autotransplantation is the organ transplantation, transplantation of Organ (anatomy), organs, Biological tissue, tissues, or even particular proteins from one part of the body to another in the same person (''wikt:auto-, auto-'' meaning "self" in Ancient Greek, Greek). The autologous tissue (also called autogenous, autogeneic, or autogenic tissue) transplanted by such a procedure is called an autograft or autotransplant. It is contrasted with allotransplantation (from other individual of the same species), Syngenic, syngeneic transplantation (grafts transplanted between two genetically identical individuals of the same species) and xenotransplantation (from other species). A common example is the removal of a piece of bone (usually from the hip) and its being ground into a paste for the reconstruction of another portion of bone. Autotransplantation, although most common with blood, bone, or skin, can be used for a wide variety of organs. One of the rare examples is autotransp ...
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Xenotransplantation
Xenotransplantation (''xenos-'' from the Greek meaning "foreign" or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenografts or xenotransplants. It is contrasted with allotransplantation (from other individual of same species), syngeneic transplantation or isotransplantation (grafts transplanted between two genetically identical individuals of the same species) and autotransplantation (from one part of the body to another in the same person). Xenotransplantation of human tumor cells into immunocompromised mice is a research technique frequently used in pre-clinical oncology research. 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. A continuing concern is that many animals, such as pigs, have a s ...
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Transplant Rejection
Transplant rejection occurs when Organ transplant, transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant. Types of transplant rejection Transplant rejection can be classified into three types: hyperacute, acute, and chronic. These types are differentiated by how quickly the recipient's immune system is activated and the specific aspect or aspects of immunity involved. Hyperacute rejection Hyperacute rejection is a form of rejection that manifests itself in the minutes to hours following transplantation. It is caused by the presence of pre-existing Antibody, antibodies in the recipient that recognize antigens in the donor organ. These antigens are located on the endothelial lining of blood vessels within the transplanted organ and, once antibodies bind, will lead to the ...
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Shaf Keshavjee
Shaf Keshavjee is a Canadian surgeon and the current Surgeon-in-Chief at University Health Network in Toronto, the Director of the Toronto Lung Transplant Program, as well as a clinical scientist and professor with the University of Toronto. His clinical practice in Thoracic Surgery and Transplant Surgery is based at the Toronto General Hospital, where he also leads a research team in lung transplantation studies. Dr. Keshavjee gained international recognition for the development of his lung preservation solution for donor lungs en route to transplantation; this solution is now the standard technique utilized by transplantation programs around the world. Further, he broke new ground with his research to the recondition and repair of injured human donor lungs, making them suitable for patient transplantation, using the Toronto XVIVO Lung Perfusion System. His work has allowed for an increase in the number of available donor lungs. Education and training In 1985, Keshavjee comple ...
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University Health Network
University Health Network (UHN) is a public research and teaching hospital network in Toronto, Ontario, Canada. It is the largest health research organization in Canada and ranks first in Canada for total research funding. It was named Canada's top research hospital by Research Infosource from 2015 to 2021. The network includes three acute care hospitals – Toronto General Hospital, Toronto Western Hospital, Princess Margaret Cancer Centre – the Toronto Rehabilitation Institute, and The Michener Institute, a post-secondary institution granting diplomas and certificates in health sciences and leadership. In the 2019-2020 fiscal year, there were over 39,000 acute inpatient stays and close to 121,000 emergency department visits across the three acute care hospitals. History A series of mergers over many years has resulted in the UHN in its current form. In 1986, the Toronto Western Hospital and the Toronto General Hospital merged to form The Toronto Hospital. This was followed in ...
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Toronto
Toronto ( ; or ) is the capital city of the Canadian province of Ontario. With a recorded population of 2,794,356 in 2021, it is the most populous city in Canada and the fourth most populous city in North America. The city is the anchor of the Golden Horseshoe, an urban agglomeration of 9,765,188 people (as of 2021) surrounding the western end of Lake Ontario, while the Greater Toronto Area proper had a 2021 population of 6,712,341. Toronto is an international centre of business, finance, arts, sports and culture, and is recognized as one of the most multicultural and cosmopolitan cities in the world. Indigenous peoples have travelled through and inhabited the Toronto area, located on a broad sloping plateau interspersed with rivers, deep ravines, and urban forest, for more than 10,000 years. After the broadly disputed Toronto Purchase, when the Mississauga surrendered the area to the British Crown, the British established the town of York in 1793 and later designat ...
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Viral Vector
Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect. Delivery of genes or other genetic material by a vector is termed transduction and the infected cells are described as transduced. Molecular biologists first harnessed this machinery in the 1970s. Paul Berg used a modified SV40 virus containing DNA from the bacteriophage λ to infect monkey kidney cells maintained in culture. In addition to their use in molecular biology research, viral vectors are used for gene therapy and the development of vaccines. Key properties of a viral vector VIRAL VECTORS are tailored to their specific applications but generally share a few key properties. *''Safety'': Although viral vectors are occasionally created from pathog ...
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Transgene
A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the phenotype of an organism. ''Transgene'' describes a segment of DNA containing a gene sequence that has been isolated from one organism and is introduced into a different organism. This non-native segment of DNA may either retain the ability to produce RNA or protein in the transgenic organism or alter the normal function of the transgenic organism's genetic code. In general, the DNA is incorporated into the organism's germ line. For example, in higher vertebrates this can be accomplished by injecting the foreign DNA into the nucleus of a fertilized ovum. This technique is routinely used to introduce human disease genes or other genes of interest into strains of laboratory mice to study the function or pathology involved with that particula ...
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Interleukin 10
Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti- inflammatory cytokine. In humans, interleukin 10 is encoded by the ''IL10'' gene. IL-10 signals through a receptor complex consisting of two IL-10 receptor-1 and two IL-10 receptor-2 proteins. Consequently, the functional receptor consists of four IL-10 receptor molecules. IL-10 binding induces STAT3 signalling via the phosphorylation of the cytoplasmic tails of IL-10 receptor 1 + IL-10 receptor 2 by JAK1 and Tyk2 respectively. Gene and protein structure The IL-10 protein is a homodimer; each of its subunits is 178-amino-acid long. IL-10 is classified as a class-2 cytokine, a set of cytokines including IL-19, IL-20, IL-22, IL-24 (Mda-7), IL-26 and interferons type-I (IFN-alpha, -beta, -epsilon, -kappa, -omega), type-II (IFN-gamma) and type-III (IFN-lambda, also known as IL-28A, IL-28B, and IL-29). Expression and synthesis In humans, IL-10 is encoded by the ''IL10'' gene, whic ...
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Rainer Blasczyk
Rainer Blasczyk (born January 8, 1962 in Castrop-Rauxel) is a German physician for transfusion medicine specialized in histocompatibility and immunogenetics in the field of organ transplantation. He is known for the development of genetic engineering of allografts to prevent organ rejection. Career Blasczyk holds a professorship in the subject at Hannover Medical School and the directorship of the institute of transfusion medicine and transplant engineering since 1998. He graduated in Medicine at the University of Essen in 1987 and began his clinical education as a junior clinician in abdominal surgery at the University of Marburg, where his interest in organ transplantation evolved. In 1988, he moved to the institute of immunology at the University of Essen, where he started to work in the field of histocompatibility and immunogenetics. From 1991 to 1993 he continued his clinical education in hematology and oncology at the University of Duesseldorf. Following these clinical year ...
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