Will Genetic Engineering Carry Xenotransplantation of Pig Islets to the Clinic?

@article{Kemter2018WillGE,
  title={Will Genetic Engineering Carry Xenotransplantation of Pig Islets to the Clinic?},
  author={Elisabeth Kemter and Joachim Denner and Eckhard Wolf},
  journal={Current Diabetes Reports},
  year={2018},
  volume={18},
  pages={1-12}
}
Purpose of ReviewPorcine islets represent a potentially attractive beta-cell source for xenotransplantation into patients with type 1 diabetes, who are not eligible to islet allo-transplantation due to a lack of suitable human donor organs. Recent progress in genetic engineering/gene editing of donor pigs provides new opportunities to overcome rejection of xeno-islets, to improve their engraftment and insulin secretion capacity, and to reduce the risk for transmission of porcine endogenous… Expand
Current status of porcine islet xenotransplantation
TLDR
The current status of islet xenotransplantation as a potential treatment for type I diabetes mellitus is detailed, focusing on recent advances in porcine xenogeneic islet production, assessment in nonhuman primate preclinical models, the outcome of human clinical trials and barriers to translation of xenoislets to the clinic. Expand
Recent progress in porcine islet isolation, culture and engraftment strategies for xenotransplantation
TLDR
A plethora of different culture media and supplements have been tested; however, a unique best culture system for NPIs is still missing and new insights, for example from single-cell analyses of islets or from stem cell differentiation toward &bgr; cells may help to optimize culture of porcine islets for xenotransplantation in an evidence-based manner. Expand
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. Expand
Progress toward islet transplantation tolerance
TLDR
This chapter provides an overview of current clinical approaches to tolerance induction as well as preclinical strategies being studied for islet tolerance, and discusses the potential immunological impact of these technologies and how they work into tolerance strategies. Expand
Xeno-organ donor pigs with multiple genetic modifications - the more the better?
TLDR
Recent developments in pig genome engineering are summarized and efforts to develop the optimum donor pig for xenotransplantation are discussed, with a speculate on how many genetic modifications may be required for initial xenotranplantation clinical trials. Expand
Integration of nano‐ and biotechnology for beta‐cell and islet transplantation in type‐1 diabetes treatment
TLDR
The iNanoBIT EU H2020 project is developing novel highly sensitive nanotechnology‐based imaging approaches allowing for monitoring of survival, engraftment, proliferation, function and whole‐body distribution of the cellular transplants in a porcine diabetes model with excellent translational potential to humans. Expand
Islet immunoisolation by macroencapsulation
TLDR
Major advances have been achieved in encapsulation technology, but there are still issues that need to be resolved associated with biocompatibility, graft oxygenation, immunoprotection, inflammatory response, and the applicable islet mass. Expand
Emerging approaches and technologies in transplantation: the potential game changers
TLDR
Three new technologies that address the key challenges to transplantation include how to best individualize and possibly eliminate the need for life-long immunosuppression, and how to expand the donor pool suitable for human transplantation. Expand
Amniotic and Umbilical Cord of Transgenic Pigs as an Alternative Source of Stem Cells.
TLDR
Tests revealed that porcine cells have a tendency to leave tissue material and adhere to plastic as human cells do, which can suggest that these cells might be tested for the presence of mesenchymal stem cells. Expand
A highly sensitive method for the detection of recombinant PERV-A/C env RNA using next generation sequencing technologies
TLDR
A highly sensitive method for the detection of PERV-A/C using next generation sequencing (NGS) technologies is developed, indicating that it would be useful for the rapid detection of Peruvian retrovirus emergence after transplantation of porcine products. Expand
...
1
2
3
...

References

SHOWING 1-10 OF 149 REFERENCES
Genetic strategies to bring islet xenotransplantation to the clinic
TLDR
The barriers to successful islet xenotransplantation are outlined, and genetic modifications that have been tested to overcome these are outlined. Expand
Pig-to-Primate Islet Xenotransplantation: Past, Present, and Future
TLDR
The results of pig-to-diabetic nonhuman primate islet xenotransplantation are steadily improving, with insulin independence being achieved for periods >1 year, and its potential for treatment of type 1 diabetes is focused on. Expand
Gene Editing, Gene Therapy, and Cell Xenotransplantation: Cell Transplantation Across Species
TLDR
Genetic modification of large animals, pigs in particular, has come a long way during the last decade, and modifications can help minimize immunological and physiological incompatibilities between porcine and human cells, thus allowing for better tolerance and function of xenocells. Expand
Xenoislets: porcine pancreatic islets for the treatment of type I diabetes
TLDR
Pig islet xenotransplantation is still a serious contestant in the race for novel treatments for type I diabetes and adequate pathogen screening, animal selection, and the establishment of microbiological, genetic, and potency release quality controls should increase safety and efficacy of future porcine islets transplantation clinical trials. Expand
Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes
TLDR
Successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression represents a previously unidentified approach to efficient cell replacement for a broad spectrum of endocrine disorders and other organ dysfunctions. Expand
Pig‐to‐Monkey Islet Xenotransplantation Using Multi‐Transgenic Pigs
  • R. Bottino, M. Wijkstrom, +9 authors M. Trucco
  • Biology, Medicine
  • American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2014
TLDR
There was evidence of reduced islet destruction in the first hours after transplantation, compared with two series of historical controls that received identical therapy but were transplanted with islets from pigs with either no or only one genetic modification. Expand
No PERV transmission during a clinical trial of pig islet cell transplantation.
TLDR
The biological safety of a second trial performed in Argentina in regards to the transmission of porcine endogenous retroviruses (PERVs) using improved detection methods is examined, providing further evidence for the safety of pig islet cell transplantation. Expand
Porcine Islet Xenografts: a Clinical Source of ß-Cell Grafts
TLDR
Genetically modified pigs, encapsulation devices, and new immune-suppressive regimens can confer graft protection, and extrahepatic transplant sites are showing promising results. Expand
Current Concepts of Using Pigs as a Source for Beta-Cell Replacement Therapy of Type 1 Diabetes
TLDR
Alternative sources of beta-cells are being developed and tested, including endocrine progenitor cells or mature beta- cells derived from pluripotent human stem cells and attempts to derive human pancreas tissue in animal hosts by interspecific chimeric complementation experiments. Expand
Optimal pig donor selection in islet xenotransplantation: current status and future perspectives
TLDR
This review discusses the suitable pig donor for islet xenotransplantation in terms of pig age, strain, structure/function of islet, and genetically modified pig. Expand
...
1
2
3
4
5
...