Pig Liver Xenotransplantation

Cooper, D. K. C.; Dou, Kefeng; Tao, Kaishan; Yang, Zhao-Xu; Tector, A. Joseph; Ekser, Burçin

doi:10.1097/tp.0000000000001319

Cited by 44 publications

(17 citation statements)

References 95 publications

(105 reference statements)

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“…However, there is a worldwide shortage of available organs from deceased donors to meet the needs of patients with fulminant liver failure or end‐stage chronic liver disease . Genetically engineered pig livers are a potential solution to this problem, and many attempts have been made to create a pig‐to‐baboon liver xenotransplantation model . Recently, Shah et al .…”

Section: Introductionmentioning

confidence: 99%

Cytokine profiles in Tibetan macaques following α‐1,3‐galactosyltransferase‐knockout pig liver xenotransplantation

Zhang

et al. 2017

Xenotransplantation

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Section: Introductionmentioning

confidence: 99%

Cytokine profiles in Tibetan macaques following α‐1,3‐galactosyltransferase‐knockout pig liver xenotransplantation

Zhang

et al. 2017

Xenotransplantation

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“…Knowledge of the genetic regulation of liver miRNA expression profiles will provide insight into haematological, biochemical and clinical–chemical biomarkers of hepatic function supporting metabolic homeostasis, innate defence and resilience. Pigs share many similarities in physiology and genome content with humans, and therefore provide an excellent model for medical research, including studies on liver transplantation [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic architecture and regulatory impact on hepatic microRNA expression linked to immune and metabolic traits

et al. 2017

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Regulation of microRNA (miRNA) expression contributes to a wide range of target gene expression and phenotypes. The miRNA expression in the liver, the central metabolic organ, was examined in 209 pigs, and integrated with haematological and clinical biomarkers of metabolic and overall health, mRNA-target expression levels and single-nucleotide polymorphism (SNP) genotypes. The expression levels of 426 miRNA species correlated with plasma haematological or biochemical traits (r² = |0.19–0.45|, false discovery rate < 5%). Pairs of these miRNAs and their predicted target mRNAs showing expressing levels associated with the identical traits were examined to understand how immune and metabolic traits are affected by miRNA-mediated regulatory networks derived by mapping miRNA abundance as an expression quantitative trait. In total, 221 miRNA-expression-QTL correspond to 164 SNPs and 108 miRNAs, including miR-34a, miR-30e, miR-148-3p, miR-204, miR-181-5p, miR-143-5p and let-7 g that also correlate with the biomarkers. Sixty-one SNPs were simultaneously associated with 29 miRNA and 41 mRNA species. The expression levels of 13 out of 29 miRNA were correlated with one of the biochemical or haematological traits. For example, the expression levels of miR-34a were correlated with serum phosphorus and cholesterin levels; miR-204, miR-15a and miR-16b were correlated with triglyceride. For haematological traits, the expression levels of miR-652 and miR-204 were correlated with the mean corpuscular haemoglobin concentration, and the expression of miR-143 was correlated with plateletcrit. Pleiotropic association analyses revealed genetic links between mRNA and miRNA on SSC6 for miR-34a, SSC9 for miR-708 and SSC14 for miR-652. Our analysis of miRNA and mRNA transcript profiles, their correlation with clinically important plasma parameters of hepatic functions as well as information on their genetic regulation provide novel regulatory networks and potential new biomarkers for immune and metabolic traits.

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“…Although limited, fairly consistent 7–9 days’ survival has been reported by different groups using GTKO and GTKO.hCD46 pig liver xenografts in NHPs after orthotopic pig liver xenotransplantation [25]. The Boston group increased survival to 29 days by the exogenous administration of human coagulation factors using the same model [26].…”

Section: Introductionmentioning

confidence: 78%

Xenotransplantation

Ekser

Li²,

Cooper³

2017

Current Opinion in Organ Transplantation

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Purpose of review To review the progress in the field of xenotransplantation with special attention to most recent encouraging findings which will eventually bring xenotransplantation to the clinic in the near future. Recent findings Starting from early 2000, with the introduction of Gal-knockout pigs, prolonged survival especially in heart and kidney xenotransplantation was recorded. However, remaining antibody barriers to nonGal antigens continue to be the hurdle to overcome. The production of genetically-engineered pigs was difficult requiring prolonged time. However, advances in gene editing, such as zinc finger nucleases, transcription activator-like effector nucleases, and most recently CRISPR technology made the production of genetically-engineered pigs easier and available to more researchers. Today, the survival of pig-to-nonhuman primate heterotopic heart, kidney, and islet xenotransplantation reached >900 days, >400 days, and >600 day, respectively. The availability of multiple-gene pigs (5 or 6 genetic modifications) and/or newer costimulation blockade agents significantly contributed to this success. Now, the field is getting ready for clinical trials with an international consensus. Summary Clinical trials in cellular or solid organ xenotransplantation are getting closer with convincing preclinical data from many centers. The next decade will show us new achievements and additional barriers in clinical xenotransplantation.

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Pig Liver Xenotransplantation

Cited by 44 publications

References 95 publications

Cytokine profiles in Tibetan macaques following α‐1,3‐galactosyltransferase‐knockout pig liver xenotransplantation

Cytokine profiles in Tibetan macaques following α‐1,3‐galactosyltransferase‐knockout pig liver xenotransplantation

Genetic architecture and regulatory impact on hepatic microRNA expression linked to immune and metabolic traits

Xenotransplantation

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