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… 
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Transgenic pigs for xenotransplantation: selection of promoter sequences for reliable transgene expression
TLDR
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
TLDR
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
TLDR
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
TLDR
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
TLDR
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.
TLDR
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
TLDR
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
TLDR
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
TLDR
In this review, the benefits and drawbacks of various genome engineering protocols, and examples of their application in xenotransplantation, are discussed.
Xenotransplantation — A special case of One Health
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