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Xenotransplantation literature update, September–October 2016

Xenotransplantation literature update, September–October 2016 Received:Nov42016   Accepted:Nov72016 DOI: 10.1111/xen.12281 LITERA TURE UPD A TE Xenotransplantation literature update, September–October AnAn Hua | Magie Steinhoff | Christopher Burlak SchultzDiabetesInstitute,Departmentof Surgery,UniversityofMinnesotaSchoolofMedicine,Minneapolis,Minnesota CorrespondenceChristopherBurlak,SchultzDiabetesInstitute,Departmentof Surgery,UniversityofMinnesotaSchoolofMedicine,Minneapolis,MN,USA. Email:christopherburlak@gmail.com KEYWORDS:CRISPR,diabetes,heart,Neu5Gc Theintroduction ofCRISPR/Cas9inxenotransplantation hasgreatly wild-type(WT)pigsforheartvalvereplacement.Leeetal. demon- enhancedtherateandefficiency intheproduction ofKOporcinecells. stratedtheirprogressintheproduction of1,3-galactosyltransferase Peterson etal.  have demonstrated the effectiveness of CRISPR/ geneknockout(GTKO)andGTKO/N-glycolylneuraminicacidgene Cas9throughthegeneration ofsixhealthyKOpiglets;fourofthesix knockout (GTKO/NeuGcKO) pigs through phenotypic screening. live-bornpigletspresentednegative for1,3-galactosyltransferaseby Reducedantibody bindingtoGTKOandGTKO/NeuGcKOGBHVs flow cytometryanalysis.Theseresultscommunicatethecapacityof comparedtoWTGBHVssubstantiates thepreferenceforKOporcine CRISPR/Cas9technologytobeusedforintracytoplasmicmicroinjec- heartvalves. tion ofporcinezygotesasasubstitute forsomatic cellnucleartransfer Successinxenografts iscontributedtoadvancesinthecharac- (SCNT)andmRNAinjections. terization oftheimmunogenicsialicacid:N-glycolylneuraminicacid Presenceofallo-andxenografts provokeB-cellactivation and (Neu5Gc). Reuven etal.  show and quantify  Neu5Gc expression proliferation ofdonor-reactive antibodies thatgreatlyreduceitslong- inporcineandbovinecardiactissues andcommercialBHVusedin termefficacy. Buermannetal. investigated theresponseofB-cell clinics.Identification andcharacterization ofxeno-antigens aidinthe activity throughincreasedstimulation oftheco-inhibitoryreceptor selectionandmodificationof KOorgans. programmedcelldeath-1(PD-1;CD279),byrecombinantagonistic Microencapsulatedneonatalporcineislets(NPI)couldprovidean solubleligandsorL23transfectantsoverexpressingthemembrane- alternative toallotransplantation andalsohelptoshieldthetrans- boundhumanPD-L1.Resultsdemonstrateddownregulation ofanti- plantedcellsfromthehumanimmunesystem;previousclinicaltrials bodyproduction whenexposedtoselectamountsofligandsbinding haveshownNPItoeectiv ff ely lowerA1clevelsanddecreaseoccur- tothePD-1receptor.Identification ofinhibitorysignalsisneces- rencesofhypoglycemia.However,thereisasignificant lossinefficacy saryfortheselection ofimmunosuppressivedrugsinthesuccessof whentheNPIaretransplantedintotheperitonealcavity,whichisdue transplantation. tolocalizedinflammation. Itohetal. demonstratedthattheNPIcould Developments of non-in vasive and time- efficient methods are regaintheirefficacy throughtargettreatmentoftheinflammation critical indetecting earlysignsofxenograft failure.Ocketal. have usinganti- TNF-alphainthemousemodel. recently developed a method in real time for evaluating immune Akeyfactorinanypreclinicaldiabetestreatmentstudyisananimal system-relatedgenesinbloodofrecipientcynomologousmonkeysbe- model.Itisimportanttoinducediabetesintheanimalmodelinaway foreandaerft transplantation. Recipientsweretransplantedwithheart thatissafe,reproducible,andreliable.ThatiswhyHeinkeetal.have orpancreatic isletsfromsingleanddouble1,3-galactosyltransferase induceddiabetesmellitusinminipigsthroughpancreatectomyand (GalT)knockout(KO)pigs.Throughphenotypicanalysisofalpha-Gal splenectomy.Thismethodleavesthepigscompletelyinsulindeficient epitopebyflow cytometryandRT PCRarrays,Ocketal.wereableto withnoclinicalsymptomsduetothelossofexocrinefunction. Heinke detectearlysignsofgraft failure.Thisnovelmethodcanhelpprolong etal. demonstratedthatthismethodcouldreplaceothersduetothe thesuccessofxenografts andaidintheselection ofimmunosuppres- factthatitwouldnotimpactotherorgansystems,suchaschemical sivedrugs. induction,anditiseectiv ff eandreliable. Shortage of human hearts has necessitated our dependence The need for xenotransplantation of hepatocytes http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Xenotransplantation Wiley

Xenotransplantation literature update, September–October 2016

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References (8)

Publisher
Wiley
Copyright
© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
ISSN
0908-665X
eISSN
1399-3089
DOI
10.1111/xen.12281
pmid
27897334
Publisher site
See Article on Publisher Site

Abstract

Received:Nov42016   Accepted:Nov72016 DOI: 10.1111/xen.12281 LITERA TURE UPD A TE Xenotransplantation literature update, September–October AnAn Hua | Magie Steinhoff | Christopher Burlak SchultzDiabetesInstitute,Departmentof Surgery,UniversityofMinnesotaSchoolofMedicine,Minneapolis,Minnesota CorrespondenceChristopherBurlak,SchultzDiabetesInstitute,Departmentof Surgery,UniversityofMinnesotaSchoolofMedicine,Minneapolis,MN,USA. Email:christopherburlak@gmail.com KEYWORDS:CRISPR,diabetes,heart,Neu5Gc Theintroduction ofCRISPR/Cas9inxenotransplantation hasgreatly wild-type(WT)pigsforheartvalvereplacement.Leeetal. demon- enhancedtherateandefficiency intheproduction ofKOporcinecells. stratedtheirprogressintheproduction of1,3-galactosyltransferase Peterson etal.  have demonstrated the effectiveness of CRISPR/ geneknockout(GTKO)andGTKO/N-glycolylneuraminicacidgene Cas9throughthegeneration ofsixhealthyKOpiglets;fourofthesix knockout (GTKO/NeuGcKO) pigs through phenotypic screening. live-bornpigletspresentednegative for1,3-galactosyltransferaseby Reducedantibody bindingtoGTKOandGTKO/NeuGcKOGBHVs flow cytometryanalysis.Theseresultscommunicatethecapacityof comparedtoWTGBHVssubstantiates thepreferenceforKOporcine CRISPR/Cas9technologytobeusedforintracytoplasmicmicroinjec- heartvalves. tion ofporcinezygotesasasubstitute forsomatic cellnucleartransfer Successinxenografts iscontributedtoadvancesinthecharac- (SCNT)andmRNAinjections. terization oftheimmunogenicsialicacid:N-glycolylneuraminicacid Presenceofallo-andxenografts provokeB-cellactivation and (Neu5Gc). Reuven etal.  show and quantify  Neu5Gc expression proliferation ofdonor-reactive antibodies thatgreatlyreduceitslong- inporcineandbovinecardiactissues andcommercialBHVusedin termefficacy. Buermannetal. investigated theresponseofB-cell clinics.Identification andcharacterization ofxeno-antigens aidinthe activity throughincreasedstimulation oftheco-inhibitoryreceptor selectionandmodificationof KOorgans. programmedcelldeath-1(PD-1;CD279),byrecombinantagonistic Microencapsulatedneonatalporcineislets(NPI)couldprovidean solubleligandsorL23transfectantsoverexpressingthemembrane- alternative toallotransplantation andalsohelptoshieldthetrans- boundhumanPD-L1.Resultsdemonstrateddownregulation ofanti- plantedcellsfromthehumanimmunesystem;previousclinicaltrials bodyproduction whenexposedtoselectamountsofligandsbinding haveshownNPItoeectiv ff ely lowerA1clevelsanddecreaseoccur- tothePD-1receptor.Identification ofinhibitorysignalsisneces- rencesofhypoglycemia.However,thereisasignificant lossinefficacy saryfortheselection ofimmunosuppressivedrugsinthesuccessof whentheNPIaretransplantedintotheperitonealcavity,whichisdue transplantation. tolocalizedinflammation. Itohetal. demonstratedthattheNPIcould Developments of non-in vasive and time- efficient methods are regaintheirefficacy throughtargettreatmentoftheinflammation critical indetecting earlysignsofxenograft failure.Ocketal. have usinganti- TNF-alphainthemousemodel. recently developed a method in real time for evaluating immune Akeyfactorinanypreclinicaldiabetestreatmentstudyisananimal system-relatedgenesinbloodofrecipientcynomologousmonkeysbe- model.Itisimportanttoinducediabetesintheanimalmodelinaway foreandaerft transplantation. Recipientsweretransplantedwithheart thatissafe,reproducible,andreliable.ThatiswhyHeinkeetal.have orpancreatic isletsfromsingleanddouble1,3-galactosyltransferase induceddiabetesmellitusinminipigsthroughpancreatectomyand (GalT)knockout(KO)pigs.Throughphenotypicanalysisofalpha-Gal splenectomy.Thismethodleavesthepigscompletelyinsulindeficient epitopebyflow cytometryandRT PCRarrays,Ocketal.wereableto withnoclinicalsymptomsduetothelossofexocrinefunction. Heinke detectearlysignsofgraft failure.Thisnovelmethodcanhelpprolong etal. demonstratedthatthismethodcouldreplaceothersduetothe thesuccessofxenografts andaidintheselection ofimmunosuppres- factthatitwouldnotimpactotherorgansystems,suchaschemical sivedrugs. induction,anditiseectiv ff eandreliable. Shortage of human hearts has necessitated our dependence The need for xenotransplantation of hepatocytes

Journal

XenotransplantationWiley

Published: Nov 1, 2016

Keywords: ; ; ;

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