Genetic engineering drives the breakthrough of pig models in liver disease research

Chenhao Xu , Xixi Fang , Xiao Xu , Xuyong Wei

Liver Research ›› 2024, Vol. 8 ›› Issue (3) : 131 -140.

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Liver Research ›› 2024, Vol. 8 ›› Issue (3) :131 -140. DOI: 10.1016/j.livres.2024.09.003
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Genetic engineering drives the breakthrough of pig models in liver disease research

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Abstract

Compared with the widely used rodents, pigs are anatomically, physiologically, and genetically more similar to humans, making them high-quality models for the study of liver diseases. Here, we review the latest research progress on pigs as a model of human liver disease, including methods for establishing them and their advantages in studying cystic fibrosis liver disease, acute liver failure, liver regeneration, non-alcoholic fatty liver disease, liver tumors, and xenotransplantation. We also emphasize the importance of genetic engineering techniques, mainly the CRISPR/Cas9 system, which has greatly enhanced the utility of porcine models as a tool for substantially advancing liver disease research. Genetic engineering is expected to propel the pig as one of the irreplaceable animal models for future biomedical research.

Keywords

Animal model / Liver disease / Genetic engineering / CRISPR/Cas9 / Xenogeneic liver transplantation / Pig

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Chenhao Xu, Xixi Fang, Xiao Xu, Xuyong Wei. Genetic engineering drives the breakthrough of pig models in liver disease research. Liver Research, 2024, 8(3): 131-140 DOI:10.1016/j.livres.2024.09.003

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Authors’ contributions

Chenhao Xu: Writing e original draft. Xixi Fang: Visualization, Investigation. Xiao Xu: Supervision. Xuyong Wei: Supervision. All authors read and approved the final version of the manuscript.

Declaration of competing interest

The authors declare that there is no conflicts of interest. All figures were created with BioRender.com.

Acknowledgements

This work was supported by the National Key Research and Development Program of China (No.2021YFA1100502, No.2021YFA1100504), the Hangzhou West Lake Pearl Project of China, and the Hangzhou New Medical Talent Project of China.

References

[1]

Groenen MA, Archibald AL, Uenishi H, et al. Analyses of pig genomes provide insight into porcine demography and evolution. Nature. 2012;491:393-398. https://doi.org/10.1038/nature11622.

[2]

Lunney JK, Van Goor A, Walker KE, Hailstock T, Franklin J, Dai C. Importance of the pig as a human biomedical model. Sci Transl Med. 2021;13:eabd5758. https://doi.org/10.1126/scitranslmed.abd5758.

[3]

Meurens F, Summerfield A, Nauwynck H, Saif L, Gerdts V. The pig: a model for human infectious diseases. Trends Microbiol. 2012;20:50-57. https://doi.org/10.1016/j.tim.2011.11.002.

[4]

Pabst R. The pig as a model for immunology research. Cell Tissue Res. 2020;380:287-304. https://doi.org/10.1007/s00441-020-03206-9.

[5]

Perleberg C, Kind A, Schnieke A. Genetically engineered pigs as models for human disease. Dis Model Mech. 2018;11:dmm030783. https://doi.org/10.1242/dmm.030783.

[6]

Schook LB, Collares TV, Darfour-Oduro KA, et al. Unraveling the swine genome: implications for human health. Annu Rev Anim Biosci. 2015;3: 219-244. https://doi.org/10.1146/annurev-animal-022114-110815.

[7]

Hou N, Du X, Wu S. Advances in pig models of human diseases. Animal Model Exp Med. 2022;5:141-152. https://doi.org/10.1002/ame2.12223.

[8]

Li WT, Zhang MM, Li QG, et al. Whole-genome resequencing reveals candidate mutations for pig prolificacy. Proc Biol Sci. 2017;284:20172437. https://doi.org/10.1098/rspb.2017.2437.

[9]

Carvalho C, Gaspar A, Knight A, Vicente L. Ethical and scientific pitfalls con-cerning laboratory research with non-human primates, and possible solu-tions. Animals (Basel). 2018;9:12. https://doi.org/10.3390/ani9010012.

[10]

Li Q, Cao M, Lei L, et al. Burden of liver cancer: from epidemiology to pre-vention. Chin J Cancer Res. 2022;34:554-566. https://doi.org/10.21147/j.issn.1000-9604.2022.06.02.

[11]

Xiao J, Wang F, Wong NK, et al. Global liver disease burdens and research trends: analysis from a Chinese perspective. J Hepatol. 2019;71:212-221. https://doi.org/10.1016/j.jhep.2019.03.004.

[12]

Shi JF, Cao M, Wang Y, et al. Is it possible to halve the incidence of liver cancer in China by 2050? Int J Cancer. 2021;148:1051-1065. https://doi.org/10.1002/ijc.33313.

[13]

Zhou J, Zhou F, Wang W, et al. Epidemiological features of NAFLD from 1999 to 2018 in China. Hepatology. 2020;71:1851-1864. https://doi.org/10.1002/hep.31150.

[14]

Lada E, Anna M, Patrik M, et al. Porcine liver anatomy applied to biomedicine. J Surg Res. 2020;250:70-79. https://doi.org/10.1016/j.jss.2019.12.038.

[15]

Lossi L, D’Angelo L, De Girolamo P, Merighi A.Anatomical features for an adequate choice of experimental animal model in biomedicine: II. Small laboratory rodents, rabbit, and pig. Ann Anat. 2016;204:11-28. https://doi.org/10.1016/j.aanat.2015.10.002.

[16]

Gasthuys E, Vandecasteele T, De Bruyne P, et al. The potential use of piglets as human pediatric surrogate for preclinical pharmacokinetic and pharmaco-dynamic drug testing. Curr Pharm Des. 2016;22:4069-4085. https://doi.org/10.2174/1381612822666160303111031.

[17]

Klem TB, Bleken E, Morberg H, Thoresen SI, Framstad T. Hematologic and biochemical reference intervals for Norwegian crossbreed grower pigs. Vet Clin Pathol. 2010;39:221-226. https://doi.org/10.1111/j.1939-165X.2009.00199.x.

[18]

Hammer C. Physiological obstacles after xenotransplantation. Ann N Y Acad Sci. 1998;862:19-27. https://doi.org/10.1111/j.1749-6632.1998.tb09113.x.

[19]

Ibrahim Z, Busch J, Awwad M, Wagner R, Wells K, Cooper DK. Selected physiologic compatibilities and incompatibilities between human and porcine organ systems. Xenotransplantation. 2006;13:488-499. https://doi.org/10.1111/j.1399-3089.2006.00346.x.

[20]

Swindle MM, Makin A, Herron AJ, Clubb Jr FJ, Frazier KS. Swine as models in biomedical research and toxicology testing. Vet Pathol. 2012;49:344-356. https://doi.org/10.1177/0300985811402846.

[21]

Shang H, Guo K, Liu Y, Yang J, Wei H. Constitutive expression of CYP3A mRNA in Bama miniature pig tissues. Gene. 2013;524:261-267. https://doi.org/10.1016/j.gene.2013.04.007.

[22]

Anzenbacherova E, Baranova J, Zuber R, et al. Model systems based on experimental animals for studies on drug metabolism in man: (mini)pig cy-tochromes P 450 3A29 and 2E1. Basic Clin Pharmacol Toxicol. 2005;96: 244-245. https://doi.org/10.1111/j.1742-7843.2005.pto960316.x.

[23]

Wright WC, Chenge J, Chen T. Structural perspectives of the CYP3A family and their small molecule modulators in drug metabolism. Liver Res. 2019;3: 132-142. https://doi.org/10.1016/j.livres.2019.08.001.

[24]

Van Peer E, Verbueken E, Saad M, Casteleyn C, Van Ginneken C, Van Cruchten S. Ontogeny of CYP3A and P-glycoprotein in the liver and the small intestine of the Göttingen minipig: an immunohistochemical evaluation. Basic Clin Pharmacol Toxicol. 2014;114:387-394. https://doi.org/10.1111/bcpt.12173.

[25]

Warr A, Affara N, Aken B, et al. An improved pig reference genome sequence to enable pig genetics and genomics research. Gigascience. 2020;9:giaa051. https://doi.org/10.1093/gigascience/giaa051.

[26]

Pan Z, Yao Y, Yin H, et al. Pig genome functional annotation enhances the biological interpretation of complex traits and human disease. Nat Commun. 2021;12:5848. https://doi.org/10.1038/s41467-021-26153-7.

[27]

Karlsson M, Sjostedt E, Oksvold P, et al. Genome-wide annotation of protein-coding genes in pig. BMC Biol. 2022;20:25. https://doi.org/10.1186/s12915-022-01229-y.

[28]

Sun HS, Yerle M, Pinton P, et al. Physical assignments of human chromosome 13 genes on pig chromosome 11 demonstrate extensive synteny and gene order conservation between pig and human. Anim Genet. 1999;30:304-308. https://doi.org/10.1046/j.1365-2052.1999.00474.x.

[29]

Sun HF, Ernst CW, Yerle M, et al. Human chromosome 3 and pig chromosome 13 show complete synteny conservation but extensive gene-order differ-ences. Cytogenet Cell Genet. 1999;85:273-278. https://doi.org/10.1159/000015312.

[30]

Hammer RE, Pursel VG, Rexroad Jr CE, et al. Production of transgenic rabbits, sheep and pigs by microinjection. Nature. 1985;315:680-683. https://doi.org/10.1038/315680a0.

[31]

Matoba S, Zhang Y. Somatic cell nuclear transfer reprogramming: mecha-nisms and applications. Cell Stem Cell. 2018;23:471-485. https://doi.org/10.1016/j.stem.2018.06.018.

[32]

Doudna JA, Charpentier E. Genome editing. The new frontier of genome en-gineering with CRISPR-Cas9. Science. 2014;346:1258096. https://doi.org/10.1126/science.1258096.

[33]

Knott GJ, Doudna JA. CRISPR-Cas guides the future of genetic engineering. Science. 2018;361:866-869. https://doi.org/10.1126/science.aat5011.

[34]

Griffith BP, Goerlich CE, Singh AK, et al. Genetically modified porcine-to-human cardiac xenotransplantation. N Engl J Med. 2022;387:35-44. https://doi.org/10.1056/NEJMoa2201422.

[35]

Fiorotto R, Amenduni M, Mariotti V, et al. Animal models for cystic fibrosis liver disease (CFLD). Biochim Biophys Acta Mol Basis Dis. 2019;1865:965-969. https://doi.org/10.1016/j.bbadis.2018.07.026.

[36]

Rogers CS, Stoltz DA, Meyerholz DK, et al. Disruption of the CFTR gene pro-duces a model of cystic fibrosis in newborn pigs. Science. 2008;321: 1837-1841. https://doi.org/10.1126/science.1163600.

[37]

Elkhadragy L, Regan MR, M Totura W, et al. Generation of genetically tailored porcine liver cancer cells by CRISPR/Cas 9 editing. Biotechniques. 2021;70: 37-48. https://doi.org/10.2144/btn-2020-0119.

[38]

Elkhadragy L, Dasteh Goli K, Totura WM, et al. Effect of CRISPR knockout of AXIN1 or ARID1A on proliferation and migration of porcine hepatocellular carcinoma. Front Oncol. 2022;12:904031. https://doi.org/10.3389/fonc.2022.904031.

[39]

Wang J, Khan SU, Cao P, et al. Construction of PIK3C 3 transgenic pig and its pathogenesis of liver damage. Life (Basel). 2022;12:630. https://doi.org/10.3390/life12050630.

[40]

Zhao H, Ye W, Guo J, et al. Development of RAG 2 (-/-) IL2Rgamma (-/Y) im-mune deficient FAH-knockout miniature pig. Front Immunol. 2022;13:950194. https://doi.org/10.3389/fimmu.2022.950194.

[41]

Ren J, Yu D, Wang J, et al. Generation of immunodeficient pig with hereditary tyrosinemia type 1 and their preliminary application for humanized liver. Cell Biosci. 2022;12:26. https://doi.org/10.1186/s13578-022-00760-3.

[42]

Hickey RD, Lillegard JB, Fisher JE, et al. Efficient production of Fah-null het-erozygote pigs by chimeric adeno-associated virus-mediated gene knockout and somatic cell nuclear transfer. Hepatology. 2011;54:1351-1359. https://doi.org/10.1002/hep.24490.

[43]

Gu P, Yang Q, Chen B, et al. Genetically blocking HPD via CRISPR-Cas 9 protects against lethal liver injury in a pig model of tyrosinemia type I. Mol Ther Methods Clin Dev. 2021;21:530-547. https://doi.org/10.1016/j.omtm.2021.04.002.

[44]

Li L, Meng H, Zou Q, et al. Establishment of gene-edited pigs expressing hu-man blood-coagulation factor VII and albumin for bioartificial liver use. J Gastroenterol Hepatol. 2019;34:1851-1859. https://doi.org/10.1111/jgh.14666.

[45]

Zhang XJ, She ZG, Wang J, et al. Multiple omics study identifies an interspecies conserved driver for nonalcoholic steatohepatitis. Sci Transl Med. 2021;13: eabg8117. https://doi.org/10.1126/scitranslmed.abg8117.

[46]

Zhang K, Tao C, Xu J, et al. CD8(þ) T cells involved in metabolic inflammation in visceral adipose tissue and liver of transgenic pigs. Front Immunol. 2021;12: 690069. https://doi.org/10.3389/fimmu.2021.690069.

[47]

Hao H, Lin R, Li Z, et al. MC4R deficiency in pigs results in hyperphagia and ultimately hepatic steatosis without high-fat diet. Biochem Biophys Res Com-mun. 2019;520:651-656. https://doi.org/10.1016/j.bbrc.2019.08.016.

[48]

Ruiz-Estevez M, Crane AT, Rodriguez-Villamil P, et al. Liver development is restored by blastocyst complementation of HHEX knockout in mice and pigs. Stem Cell Res Ther. 2021;12:292. https://doi.org/10.1186/s13287-021-02348-z.

[49]

Shteinberg M, Haq IJ, Polineni D, Davies JC. Cystic fibrosis. Lancet. 2021;397: 2195-2211. https://doi.org/10.1016/s0140-6736(20)32542-3.

[50]

Fiorotto R, Strazzabosco M. Pathophysiology of cystic fibrosis liver disease: a channelopathy leading to alterations in innate immunity and in microbiota. Cell Mol Gastroenterol Hepatol. 2019;8:197-207. https://doi.org/10.1016/j.jcmgh.2019.04.013.

[51]

Dana J, Debray D, Beaufrere A, et al. Cystic fibrosis-related liver disease: clinical presentations, diagnostic and monitoring approaches in the era of CFTR modulator therapies. J Hepatol. 2022;76:420-434. https://doi.org/10.1016/j.jhep.2021.09.042.

[52]

Toledano MB, Mukherjee SK, Howell J, et al. The emerging burden of liver disease in cystic fibrosis patients: a UK nationwide study. PLoS One. 2019;14: e0212779. https://doi.org/10.1371/journal.pone.0212779.

[53]

Guilbault C, Saeed Z, Downey GP, Radzioch D. Cystic fibrosis mouse models. Am J Respir Cell Mol Biol. 2007;36:1-7. https://doi.org/10.1165/rcmb.2006-0184TR.

[54]

Rogers CS, Hao Y, Rokhlina T, et al. Production of CFTR-null and CFTR-DeltaF 508 heterozygous pigs by adeno-associated virus-mediated gene tar-geting and somatic cell nuclear transfer. J Clin Invest. 2008;118:1571e1577: 10.1111/xen.12289. https://doi.org/10.1172/JCI34773.

[55]

Meyerholz DK, Stoltz DA, Pezzulo AA, Welsh MJ. Pathology of gastrointestinal organs in a porcine model of cystic fibrosis. Am J Pathol. 2010;176: 1377-1389. https://doi.org/10.2353/ajpath.2010.090849.

[56]

Uc A, Giriyappa R, Meyerholz DK, et al. Pancreatic and biliary secretion are both altered in cystic fibrosis pigs. Am J Physiol Gastrointest Liver Physiol. 2012;303:G961eG968. https://doi.org/10.1152/ajpgi.00030.2012.

[57]

Terblanche J, Hickman R. Animal models of fulminant hepatic failure. Dig Dis Sci. 1991;36:770-774. https://doi.org/10.1007/BF01311235.

[58]

van de Kerkhove MP, Hoekstra R, van Gulik TM, Chamuleau RAFM. Large animal models of fulminant hepatic failure in artificial and bioartificial liver support research. Biomaterials. 2004;25:1613-1625. https://doi.org/10.1016/s0142-9612(03)00509-x.

[59]

Filipponi F, Boggi U, Meacci L, et al. A new technique for total hepatectomy in the pig for testing liver support devices. Surgery. 1999;125:448-455.

[60]

Filipponi F, Fabbri LP, Marsili M, et al. A new surgical model of acute liver failure in the pig: experimental procedure and analysis of liver injury. Eur Surg Res. 1991;23:58-64. https://doi.org/10.1159/000129137.

[61]

Xue W, Fu Y, Zhang H, et al. A novel, simplified, and reproducible porcine model of acute ischemic liver failure with portal vein preservation. Exp Anim. 2022;71:60-70. https://doi.org/10.1538/expanim.21-0076.

[62]

Lee KC, Palacios Jimenez C, Alibhai H, et al. A reproducible, clinically relevant, intensively managed, pig model of acute liver failure for testing of therapies aimed to prolong survival. Liver Int. 2013;33:544-551. https://doi.org/10.1111/liv.12042.

[63]

Sun H, Ni HM, McCracken JM, et al. Liver-specific deletion of mechanistic target of rapamycin does not protect against acetaminophen-induced liver injury in mice. Liver Res. 2021;5:79-87. https://doi.org/10.1016/j.livres.2021.03.001.

[64]

Wang J, Sun Z, Jiang J, et al. Proteomic signature of acute liver failure: from discovery and verification in a pig model to confirmation in humans. Mol Cell Proteomics. 2017;16:1188-1199. https://doi.org/10.1074/mcp.M117.067397.

[65]

Yuasa T, Yamamoto T, Rivas-Carrillo JD, et al. Laparoscopy-assisted creation of a liver failure model in pigs. Cell Transplant. 2008;17:187-193. https://doi.org/10.3727/000000008783906973.

[66]

Abbasnezhad A, Salami F, Mohebbati R. A review: systematic research approach on toxicity model of liver and kidney in laboratory animals. Animal Model Exp Med. 2022;5:436-444. https://doi.org/10.1002/ame2.12230.

[67]

Newsome PN, Plevris JN, Nelson LJ, Hayes PC. Animal models of fulminant hepatic failure: a critical evaluation. Liver Transpl. 2000;6:21-31. https://doi.org/10.1002/lt.500060110.

[68]

Kalsi RS, Ostrowska A, Olson A, et al. A non-human primate model of acute liver failure suitable for testing liver support systems. Front Med (Lausanne). 2022;9:964448. https://doi.org/10.3389/fmed.2022.964448.

[69]

Yagi S, Hirata M, Miyachi Y, Uemoto S. Liver regeneration after hepatectomy and partial liver transplantation. Int J Mol Sci. 2020;21:8414. https://doi.org/10.3390/ijms21218414.

[70]

Court FG, Laws PE, Morrison CP, et al. Subtotal hepatectomy: a porcine model for the study of liver regeneration. J Surg Res. 2004;116:181-186. https://doi.org/10.1016/j.jss.2003.08.007.

[71]

Golriz M, Ashrafi M, Khajeh E, Majlesara A, Flechtenmacher C, Mehrabi A. Establishing a porcine model of small for size syndrome following liver resection. Can J Gastroenterol Hepatol. 2017;2017:5127178. https://doi.org/10.1155/2017/5127178.

[72]

Kahn D, Hickman R, Terblanche J. A porcine model for the study of liver regeneration. J Invest Surg. 1988;1:139-142. https://doi.org/10.3109/08941938809141086.

[73]

Mortensen KE, Conley LN, Hedegaard J, et al. Regenerative response in the pig liver remnant varies with the degree of resection and rise in portal pressure. Am J Physiol Gastrointest Liver Physiol. 2008;294:G819eG830. https://doi.org/10.1152/ajpgi.00179.2007.

[74]

Inomata K, Tajima K, Yagi H, et al. A pre-clinical large animal model of sus-tained liver injury and regeneration stimulus. Sci Rep. 2018;8:14987. https://doi.org/10.1038/s41598-018-32889-y.

[75]

Zwirner S, Abu Rmilah AA, Klotz S, et al. First-in-class MKK 4 inhibitors enhance liver regeneration and prevent liver failure. Cell. 2024;187: 1666-1684.e26. https://doi.org/10.1016/j.cell.2024.02.023.

[76]

Hickey RD, Mao SA, Glorioso J, et al. Curative ex vivo liver-directed gene therapy in a pig model of hereditary tyrosinemia type 1. Sci Transl Med. 2016;8:349ra99. https://doi.org/10.1126/scitranslmed.aaf3838.

[77]

Sheka AC, Adeyi O, Thompson J, Hameed B, Crawford PA, Ikramuddin S. Nonalcoholic steatohepatitis: a review. JAMA. 2020;323:1175-1183. https://doi.org/10.1001/jama.2020.2298.

[78]

Ibrahim SH, Hirsova P, Malhi H, Gores GJ. Animal models of nonalcoholic steatohepatitis: eat, delete, and inflame. Dig Dis Sci. 2016;61:1325-1336. https://doi.org/10.1007/s10620-015-3977-1.

[79]

Lee L, Alloosh M, Saxena R, et al. Nutritional model of steatohepatitis and metabolic syndrome in the Ossabaw miniature swine. Hepatology. 2009;50: 56-67. https://doi.org/10.1002/hep.22904.

[80]

Liang T, Alloosh M, Bell LN, et al. Liver injury and fibrosis induced by dietary challenge in the Ossabaw miniature Swine. PLoS One. 2015;10:e0124173. https://doi.org/10.1371/journal.pone.0124173.

[81]

Schumacher-Petersen C, Christoffersen BO, Kirk RK, et al. Experimental non-alcoholic steatohepatitis in Göttingen Minipigs: consequences of high fat-fructose-cholesterol diet and diabetes. J Transl Med. 2019;17:110. https://doi.org/10.1186/s12967-019-1854-y.

[82]

Maj M, Harbottle B, Thomas PA, et al. Consumption of high-fructose corn syrup compared with sucrose promotes adiposity and increased triglycer-idemia but comparable NAFLD severity in juvenile iberian pigs. J Nutr. 2021;151:1139-1149. https://doi.org/10.1093/jn/nxaa441.

[83]

Schmidt NH, Svendsen P, Albarran-Juarez J, Moestrup SK, Bentzon JF. High-fructose feeding does not induce steatosis or non-alcoholic fatty liver disease in pigs. Sci Rep. 2021;11:2807. https://doi.org/10.1038/s41598-021-82208-1.

[84]

Christoffersen B, Golozoubova V, Pacini G, Svendsen O, Raun K. The young Gottingen minipig as a model of childhood and adolescent obesity: influence of diet and gender. Obesity (Silver Spring). 2013;21:149-158. https://doi.org/10.1002/oby.20249.

[85]

Christoffersen BO, Grand N, Golozoubova V, Svendsen O, Raun K. Gender-associated differences in metabolic syndrome-related parameters in Gottin-gen minipigs. Comp Med. 2007;57:493-504.

[86]

Hewitt KN, Pratis K, Jones ME, Simpson ER. Estrogen replacement reverses the hepatic steatosis phenotype in the male aromatase knockout mouse. Endo-crinology. 2004;145:1842-1848. https://doi.org/10.1210/en.2003-1369.

[87]

Cao D, Cao QM, Subramaniam S, et al. Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity. Proc Natl Acad Sci U S A. 2017;114:6914-6923. https://doi.org/10.1073/pnas.1705446114.

[88]

Halsted CH, Villanueva JA, Devlin AM. Folate deficiency, methionine meta-bolism, and alcoholic liver disease. Alcohol. 2002;27:169-172. https://doi.org/10.1016/s0741-8329(02)00225-2.

[89]

Johansen MV, Bogh HO, Nansen P, Christensen NO. Schistosoma japonicum infection in the pig as a model for human schistosomiasis japonica. Acta Trop. 2000;76:85-99. https://doi.org/10.1016/s0001-706x(00)00103-0.

[90]

Hutchinson L, Kirk R. High drug attrition rates-where are we going wrong? Nat Rev Clin Oncol. 2011;8:189-190. https://doi.org/10.1038/nrclinonc.2011.34.

[91]

Li X, Zhou X, Guan Y, Wang YX, Scutt D, Gong QY. N-nitrosodiethylamine-induced pig liver hepatocellular carcinoma model: radiological and histo-pathological studies. Cardiovasc Intervent Radiol. 2006;29:420-428. https://doi.org/10.1007/s00270-005-0099-8.

[92]

Ho J, Ware M, Law J, et al. Improved, Shorter-latency carcinogen-induced hepatocellular carcinoma model in pigs. Oncology. 2018;95:360-369. https://doi.org/10.1159/000491092.

[93]

Robertson N, Schook LB, Schachtschneider KM. Porcine cancer models: po-tential tools to enhance cancer drug trials. Expet Opin Drug Discov. 2020;15: 893-902. https://doi.org/10.1080/17460441.2020.1757644.

[94]

Schachtschneider KM, Schwind RM, Darfour-Oduro KA, et al. A validated, transitional and translational porcine model of hepatocellular carcinoma. Oncotarget. 2017;8:63620-63634. https://doi.org/10.18632/oncotarget.18872.

[95]

Gaba RC, Elkhadragy L, Boas FE, et al. Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation. Oncotarget. 2020;11:2686-2701. https://doi.org/10.18632/oncotarget.27647.

[96]

Ling S, Jiang G, Que Q, Xu S, Chen J, Xu X. Liver transplantation in patients with liver failure: twenty years of experience from China. Liver Int. 2022;42: 2110-2116. https://doi.org/10.1111/liv.15288.

[97]

Lamm V, Ekser B, Vagefi PA, Cooper DKC. Bridging to allotransplantation-is pig liver xenotransplantation the best option? Transplantation. 2022;106:26-36. https://doi.org/10.1097/TP.0000000000003722.

[98]

Ladowski JM, Houp J, Hauptfeld-Dolejsek V, Javed M, Hara H, Cooper DKC. Aspects of histocompatibility testing in xenotransplantation. Transpl Immunol. 2021;67:101409. https://doi.org/10.1016/j.trim.2021.101409.

[99]

Ryczek N, Hryhorowicz M, Zeyland J, Lipinski D, Slomski R. CRISPR/Cas technology in pig-to-human xenotransplantation research. Int J Mol Sci. 2021;22:3196. https://doi.org/10.3390/ijms22063196.

[100]

Ekser B, Burlak C, Waldman JP, et al. Immunobiology of liver xeno-transplantation. Expert Rev Clin Immunol. 2012;8:621-634. https://doi.org/10.1586/eci.12.56.

[101]

Zhang X, Li X, Yang Z, et al. A review of pig liver xenotransplantation: current problems and recent progress. Xenotransplantation. 2019;26:e12497. https://doi.org/10.1111/xen.12497.

[102]

Chen G, Qian H, Starzl T, et al. Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys. Nat Med. 2005;11:1295-1298. https://doi.org/10.1038/nm1330.

[103]

Zhou Q, Li T, Wang K, et al. Current status of xenotransplantation research and the strategies for preventing xenograft rejection. Front Immunol. 2022;13: 928173. https://doi.org/10.3389/fimmu.2022.928173.

[104]

Song KH, Kang YJ, Jin UH, et al. Cloning and functional characterization of pig CMP-N-acetylneuraminic acid hydroxylase for the synthesis of N-glyco-lylneuraminic acid as the xenoantigenic determinant in pig-human xeno-transplantation. Biochem J. 2010;427:179-188. https://doi.org/10.1042/BJ20090835.

[105]

Byrne G, Ahmad-Villiers S, Du Z, McGregor C. B4GALNT2 and xeno-transplantation: a newly appreciated xenogeneic antigen. Xeno-transplantation. 2018;25:e12394. https://doi.org/10.1111/xen.12394.

[106]

Cooper DKC, Hara H, Iwase H, et al. Justification of specific genetic modifi-cations in pigs for clinical organ xenotransplantation. Xenotransplantation. 2019;26:e12516. https://doi.org/10.1111/xen.12516.

[107]

Estrada JL, Martens G, Li P, et al. Evaluation of human and non-human primate antibody binding to pig cells lacking GGTA1/CMAH/beta4GalNT 2 genes. Xenotransplantation. 2015;22:194-202. https://doi.org/10.1111/xen.12161.

[108]

Butler JR, Skill NJ, Priestman DL, et al. Silencing the porcine iGb3s gene does not affect Galalpha3Gal levels or measures of anticipated pig-to-human and pig-to-primate acute rejection. Xenotransplantation. 2016;23:106-116. https://doi.org/10.1111/xen.12217.

[109]

Li P, Estrada JL, Burlak C, et al. Efficient generation of genetically distinct pigs in a single pregnancy using multiplexed single-guide RNA and carbohydrate selec-tion. Xenotransplantation. 2015;22:20-31. https://doi.org/10.1111/xen.12131.

[110]

Fischer K, Kraner-Scheiber S, Petersen B, et al. Efficient production of multi-modified pigs for xenotransplantation by 'combineering', gene stacking and gene editing. Sci Rep. 2016;6:29081. https://doi.org/10.1038/srep29081.

[111]

Niu D, Wei HJ, Lin L, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9. Science. 2017;357:1303-1307. https://doi.org/10.1126/science.aan4187.

[112]

Hume DM, Merrill JP, Miller BF, Thorn GW. Experiences with renal homo-transplantation in the human: report of nine cases. J Clin Invest. 1955; 34:327-382. https://doi.org/10.1172/JCI103085.

[113]

Adams AB, Kim SC, Martens GR, et al. Xenoantigen deletion and chemical immunosuppression can prolong renal xenograft survival. Ann Surg. 2018;268:564-573. https://doi.org/10.1097/SLA.0000000000002977.

[114]

Langin M, Mayr T, Reichart B, et al. Consistent success in life-supporting porcine cardiac xenotransplantation. Nature. 2018;564:430-433. https://doi.org/10.1038/s41586-018-0765-z.

[115]

Calne RY, White HJ, Herbertson BM, et al. Pig-to-baboon liver xenografts. Lancet. 1968;1:1176-1188. https://doi.org/10.1016/s0140-6736(68)91869-2.

[116]

Ramirez P, Chavez R, Majado M, et al. Life-supporting human complement regulator decay accelerating factor transgenic pig liver xenograft maintains the metabolic function and coagulation in the nonhuman primate for up to 8 days. Transplantation. 2000;70:989-998. https://doi.org/10.1097/00007890-200010150-00001.

[117]

Ekser B, Long C, Echeverri GJ, et al. Impact of thrombocytopenia on survival of baboons with genetically modified pig liver transplants: clinical relevance. Am J Transplant. 2010;10:273-385. https://doi.org/10.1111/j.1600-6143.2009.02945.x.

[118]

Kim K, Schuetz C, Elias N, et al. Up to 9-day survival and control of throm-bocytopenia following alpha1,3-galactosyl transferase knockout swine liver xenotransplantation in baboons. Xenotransplantation. 2012;19:256-264. https://doi.org/10.1111/j.1399-3089.2012.00717.x.

[119]

Shah JA, Patel MS, Elias N, et al. Prolonged survival following pig-to-primate liver xenotransplantation utilizing exogenous coagulation factors and cos-timulation blockade. Am J Transplant. 2017;17:2178-2185. https://doi.org/10.1111/ajt.14341.

[120]

Iwase H, Liu H, Schmelzer E, et al. Transplantation of hepatocytes from genetically engineered pigs into baboons. Xenotransplantation. 2017;24: 10.1111/xen. 12289. https://doi.org/10.1111/xen.12289.

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