Importance of the pig as a human biomedical model

Lunney, Joan K.; Goor, Angelica Van; Walker, Kristen; Hailstock, Taylor; Franklin, Jasmine; Dai, Chaohui

doi:10.1126/scitranslmed.abd5758

Cited by 382 publications

(276 citation statements)

References 229 publications

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“…Additionally, our genome editing technologies in pigs could have other application and benefit. For instance, our work has tremendous effects on upgrading current and future pig biomedical models, while humanized (gene edited) pig models can be utilized in preclinical research 17 . Besides, since the pig is also an important food source, people could apply these genome editing technologies for generating the specific food for certain patients.For example, the U.S FDA has recently authorized the GalSafe gene edited pigs 18,19 as the food to help people who are under the effects of tick bite–induced allergic reactions to the sugar, galactose, which is also known as galactose-α1,3-galactose (α-Gal) syndrome (Figure 5).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Viable Selective Germline Genome Edited Pigs Skin Xenotransplants in Patients with Thermal Burns

Zou

zhang

et al. 2022

Preprint

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Background: Rapid closure of open wound, either temporarily or perpetually, is recognized as the standard of care in patients with thermal burns. Human cadaveric allograft and simple genetically modified porcine xenografts are not able to provide enough durable time for extensively burned patients. A selective germline genome edited pig (SGGEP) skin xenograft, Xeno X skin, would be a valuable candidate to the clinical options. Methods: In an ongoing investigator-initiated clinical trial in patients with thermal burns, the efficacy and safety of cryopreserved Xeno X skin grafts of SGGEP for burned patients were evaluated. Each patient received surgical grafting with a skin xenotransplant and wild type pig extracellular matrix (wpECM) in a side-by-side manner for in-situ comparison. The primary outcome measures of xeno-skin grafts included Xeno X skin safety and tolerability, as well as the quality and duration of temporary barrier function yielded by Xeno X skin grafts (as determined by Baux score). Seven parameters included in the analysis were vascularization, pigmentation, thickness, relief, pliability, surface area and the overall opinion, with each calculated on an independent 0-10 scale. Results: A total of 16 burned patients completed the trial. All the patients tolerated Xeno X skin grafts well and no advent events were observed. In all cases, Xeno X skin grafts were vascularized and fully adherent, they also exhibited better overall outcomes than those of wpECM. Xeno X skin grafts survived for at least 25 days without a need of any immunosuppressive drug, well consistent with our earlier preclinical studies in non- human primates. Conclusion: Xeno X skin grafts of SGGEP did not incur any signs of local and systemic safety issues, and in the meanwhile provided a high quality and long duration of temporary barrier function for burned patients. This is a major milestone in the xenotransplant field, indicating that genome-edited organ xenotransplant has become a clinical reality.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Viable Selective Germline Genome Edited Pigs Skin Xenotransplants in Patients with Thermal Burns

Zou

zhang

et al. 2022

Preprint

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“…These studies would be valuable for both animal welfare and the industry. Likewise, these epigenetic investigations would also be valuable for translational studies, as the porcine model is a well-known standard for human studies [ 109 , 110 ].…”

Section: Epigenetics Studies In the Porcine Modelmentioning

confidence: 99%

How Epigenetics Can Enhance Pig Welfare?

Silva

Araujo

Pértille

et al. 2021

Animals

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Epigenetics works as an interface between the individual and its environment to provide phenotypic plasticity to increase individual adaptation capabilities. Recently, a wide variety of epi-genetic findings have indicated evidence for its application in the development of putative epi-biomarkers of stress in farm animals. The purpose of this study was to evaluate previously reported stress epi-biomarkers in swine and encourage researchers to investigate potential paths for the development of a robust molecular tool for animal welfare certification. In this literature review, we report on the scientific concerns in the swine production chain, the management carried out on the farms, and the potential implications of these practices for the animals’ welfare and their epigenome. To assess reported epi-biomarkers, we identified, from previous studies, potentially stress-related genes surrounding epi-biomarkers. With those genes, we carried out a functional enrichment analysis of differentially methylated regions (DMRs) of the DNA of swine subjected to different stress-related conditions (e.g., heat stress, intrauterine insult, and sanitary challenges). We identified potential epi-biomarkers for target analysis, which could be added to the current guidelines and certification schemes to guarantee and certify animal welfare on farms. We believe that this technology may have the power to increase consumers’ trust in animal welfare.

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“…Pigs (Sus scrofa) have great potential as biomedical models for studying developmental processes, congenital diseases and pathogen response mechanisms and can be used as xenotransplant organ donors and tools for vaccine and drug design [1,2]. Minipigs are also broadly used in several fields of biomedicine, e.g., experimental surgery, pharmacology, toxicology and basic research (for review see [3][4][5][6]).…”

Section: Introductionmentioning

confidence: 99%

“…1 PERV pol were detected using a real-time PCR, and the numbers indicate the Ct value; PERV-C and PERV-A/C were detected using a conventional PCR.…”

mentioning

confidence: 99%

Virological and Parasitological Characterization of Mini-LEWE Minipigs Using Improved Screening Methods and an Overview of Data on Various Minipig Breeds

et al. 2021

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Minipigs play an important role in biomedical research and have also been used as donor animals in xenotransplantation. To serve as a donor in xenotransplantation, the animals must be free of potential zoonotic viruses, bacteria and parasites. Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs and cannot be eliminated as most of the other pig viruses can. PERV-A and PERV-B infect human cells in cell culture and are integrated in all pigs, whereas PERV-C infects only pig cells and it is found in many, but not all pigs. Minipigs are known for a high prevalence of recombinant PERV-A/C viruses able to infect human cells (Denner and Schuurman, Viruses, 2021;13:1869). Here, Mini-LEWE minipigs are screened for the first time for pig viruses including PERV. Peripheral blood mononuclear cells (PBMCs) from 10 animals were screened using PCR-based methods (PCR, RT-PCR, and real-time PCR). In comparison with our previous screening assays, numerous improvements were introduced, e.g., the usage of gene blocks as a PCR standard and foreign RNA to control reverse transcription in RT-PCR. Using these improved detection methods, Mini-LEWE pigs were found to be negative for porcine cytomegalovirus (PCMV), porcine lymphotropic herpesviruses (PLHV-1, -2 and -3), porcine circoviruses (PCV1, 2, 3 and 4), porcine parvovirus (PPV) and hepatitis E virus (HEV). All animals carried PERV-A, PERV-B and PERV-C in their genome. PERV-A/C was not found. In contrast to all other minipig breeds (Göttingen minipigs, Aachen minipigs, Yucatan micropig, Massachusetts General Hospital miniature pigs), Mini-LEWE minipigs have less viruses and no PERV-A/C. Parasitological screening showed that none of the Mini-LEWE minipigs harbored ecto- and gastrointestinal parasites, but at least one animal tested positive for anti-Toxoplasma gondii antibodies.

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Importance of the pig as a human biomedical model

Abstract: Pigs are important biomedical models for studying human development and disease, for xenotransplant organ donors, and for vaccine and drug design.

Cited by 382 publications

References 229 publications

Efficacy and Safety of Viable Selective Germline Genome Edited Pigs Skin Xenotransplants in Patients with Thermal Burns

Efficacy and Safety of Viable Selective Germline Genome Edited Pigs Skin Xenotransplants in Patients with Thermal Burns

How Epigenetics Can Enhance Pig Welfare?

Virological and Parasitological Characterization of Mini-LEWE Minipigs Using Improved Screening Methods and an Overview of Data on Various Minipig Breeds

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