Genetic modification of pigs as organ donors for xenotransplantation
@article{Klymiuk2010GeneticMO, title={Genetic modification of pigs as organ donors for xenotransplantation}, author={Nikolai Klymiuk and Bernhard Aigner and Gottfried Brem and Eckhard Wolf}, journal={Molecular Reproduction and Development}, year={2010}, volume={77} }
Transgenic pigs are promising donor organisms for xenotransplantation as they share many anatomical and physiological characteristics with humans. The most profound barrier to pig‐to‐primate xenotransplantation is the rejection of the grafted organ by a cascade of immune mechanisms commonly referred to as hyperacute rejection (HAR), acute humoral xenograft rejection (AHXR), immune cell‐mediated rejection, and chronic rejection. Various strategies for the genetic modification of pigs facilitate…
163 Citations
Transgenic pigs for xenotransplantation: selection of promoter sequences for reliable transgene expression
- Biology, MedicineCurrent opinion in organ transplantation
- 2010
Comparison of regulatory sequences from various species indicates that carefully selected porcine promoter sequences may be beneficial to achieve this aim of accurate spatiotemporal expression of immunomodulatory and anticoagulant proteins on the endothelial cells of transgenic pigs.
Genetically modified pigs as donors of cells, tissues, and organs for xenotransplantation
- Medicine, BiologyAnimal frontiers : the review magazine of animal agriculture
- 2019
This work has shown that pigs can be optimized by genetic engineering as a source of cells, tissues, and organs for xenotransplantation, and advances in gen(om)e editing are speeding up progress in this field.
New Concepts of Immune Modulation in Xenotransplantation
- Biology, MedicineTransplantation
- 2013
Before xenotransplantation can be introduced successfully into the clinic, the problems of the innate, coagulopathic, and inflammatory responses will have to be overcome, most likely by the transplantation of organs from genetically engineered pigs.
Advances in organ transplant from pigs
- Biology, MedicineScience
- 2017
Inactivation of PERVs in the pig genome increases the safety of xenotransplantation, and Niu et al. (1) demonstrate how to increase the safetyof xenotranplantation.
Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses
- Biology, MedicineClinical Microbiology Reviews
- 2012
Highly sensitive and specific methods have been developed to analyze the PERV status of donor pigs and to monitor recipients for PERV infection, including selection of PERV-C-negative, low-producer pigs, generation of an effective vaccine, selection of effective antiretrovirals, and generation of animals transgenic for a PERv-specific short hairpin RNA inhibiting PERV expression by RNA interference.
Overcoming Coagulation Dysregulation in Pig Solid Organ Transplantation in Nonhuman Primates: Recent Progress.
- Biology, MedicineTransplantation
- 2018
There is a realistic prospect that the transplantation of a kidney or heart, in combination with a conventional immunosuppressive regimen, will enable long-term recipient survival, in view of the more complex coagulation dysfunction seen after pig liver and lung transplantation.
ITIM‐dependent negative signaling pathways for the control of cell‐mediated xenogeneic immune responses
- Biology, MedicineXenotransplantation
- 2013
The delivery of immunoreceptor tyrosine‐based inhibitory motif (ITIM)‐dependent and related negative signals to control innate and adaptive T and B cells might overcome cell‐mediated xenogeneic immunity.
Xenotransplantation: immunological hurdles and progress toward tolerance
- Biology, MedicineImmunological reviews
- 2014
It is believed that the addition of further beneficial transgenes to Gal knockout swine, combined with new therapies such as Treg administration, will allow for successful clinical application of xenotransplantation.
Genome Engineering for Xenotransplantation
- Biology, Engineering
- 2019
In this review, the benefits and drawbacks of various genome engineering protocols, and examples of their application in xenotransplantation, are discussed.
References
SHOWING 1-10 OF 87 REFERENCES
Expression of a functional human complement inhibitor in a transgenic pig as a model for the prevention of xenogeneic hyperacute organ rejection.
- Biology, MedicineProceedings of the National Academy of Sciences of the United States of America
- 1994
A strategy for developing a pig-to-primate xenogeneic transplantation model to test whether the expression of a human complement inhibitor in transgenic pigs could render Xenogeneic organs resistant to hyperacute rejection is demonstrated.
Transgenic pigs designed to express human CD59 and H‐transferase to avoid humoral xenograft rejection
- BiologyXenotransplantation
- 2002
Transgenic pigs that coexpress hCD59 and HT in various cells and tissues are developed to address both natural antibody binding and complement activation and suggest that engineering donor pigs to express multiple molecules that address different humoral components of Xenograft rejection represents an important step toward enhancing xenograft survival and improving the prospect of clinical xenotransplantation.
Characterization of transgenic pigs expressing functionally active human CD59 on cardiac endothelium.
- Biology, MedicineTransplantation
- 1996
Evidence is presented that shows that the low level of human CD59 protein expression in the porcine heart inhibits membrane attack complex assembly and reduces tissue damage when the heart is transplanted to a baboon, supporting the concept that the species specific function of CRPs contributes to the humoral barrier to xenotransplantation.
A HUMAN CD46 TRANSGENIC PIG MODEL SYSTEM FOR THE STUDY OF DISCORDANT XENOTRANSPLANTATION
- Biology, MedicineTransplantation
- 2001
This is the first report to describe generation of transgenic pigs that express human CD46, and the first in vivo demonstration of the ability of humanCD46 expressed on pig organs to regulate complement activation and overcome hyperacute rejection upon transplantation of a vascularized organ into nonhuman primates.
The perspectives for porcine-to-human xenografts.
- Medicine, BiologyComparative immunology, microbiology and infectious diseases
- 2009
Expression of Biologically Active Human TRAIL in Transgenic Pigs
- Biology, MedicineTransplantation
- 2005
Ubiquitous expression of human TRAIL was achieved in transgenic pigs without detrimental side effects and will be used for future xenotransplantation experiments to modulate primate anti-pig cellular immune responses.
Current cellular innate immune hurdles in pig-to-primate xenotransplantation
- BiologyCurrent opinion in organ transplantation
- 2008
Cellular human innate immune responses are increasingly recognized as barriers to successful pig-to-human xenotransplantation, and only a detailed knowledge of the molecular mechanisms involved will allow us to overcome this barrier.
TISSUE EXPRESSION OF HUMAN COMPLEMENT INHIBITOR, DECAY‐ACCELERATING FACTOR, IN TRANSGENIC PIGS A POTENTIAL APPROACH FOR PREVENTING XENOGRAFT REJECTION
- Biology, MedicineTransplantation
- 1995
Since complement-mediated hyperacute rejection of xenografts prevents the use of pigs as organ donors to man, the development of transgenic animals expressing species-specific complement inhibitors…
Characterization of a CD46 transgenic pig and protection of transgenic kidneys against hyperacute rejection in non‐immunosuppressed baboons
- Biology, MedicineXenotransplantation
- 2004
The expression levels, tissue distribution and in vitro functional tests indicate highly efficient CD46 function, controlling both classical and alternative pathway complement activation, which suggests it might be the complement regulator of choice to protect xenografts.
Transgenic expression of CTLA4-Ig by fetal pig neurons for xenotransplantation
- Biology, MedicineTransgenic Research
- 2004
Data show that neurons from transgenic pigs express hCTLA4-Ig in situ and support the use of this material in future pre-clinical trials in neuron xenotransplantation.