Name: a rabbit model of durable transgene expression in jugular vein to common carotid artery interposition grafts
Uploaded: 2018-09-10T12:30:00.000+00:00
Duration: 13 min 58 s
Description: Watch this Scientific Journal Video about A Rabbit Model of Durable Transgene Expression in Jugular Vein to Common Carotid Artery Interposition Grafts at JoVE.com

<ol>
	<li>Libby, P., Bornfeldt, K. E., Tall, A. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Atherosclerosis:+Successes,+Surprises,+and+Future+Challenges.">Atherosclerosis: Successes, Surprises, and Future Challenges.</a> Circ Res. 118, 531-534 (2016).</li><li>Fowkes, F. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+global+estimates+of+prevalence+and+risk+factors+for+peripheral+artery+disease+in+2000+and+2010:+a+systematic+review+and+analysis.">Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis.</a> Lancet. 382, 1329-1340 (2013).</li><li>Mohr, F. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coronary+artery+bypass+graft+surgery+versus+percutaneous+coronary+intervention+in+patients+with+three-vessel+disease+and+left+main+coronary+disease:+5-year+follow-up+of+the+randomised,+clinical+SYNTAX+trial.">Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial.</a> Lancet. 381, 629-638 (2013).</li><li>de Vries, M. R., Simons, K. H., Jukema, J. W., Braun, J., Quax, P. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vein+graft+failure:+from+pathophysiology+to+clinical+outcomes.">Vein graft failure: from pathophysiology to clinical outcomes.</a> Nat Rev Cardiol. 13 (8), 451-470 (2016).</li><li>Harskamp, R. E., Lopes, R. D., Baisden, C. E., de Winter, R. J., Alexander, J. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Saphenous+vein+graft+failure+after+coronary+artery+bypass+surgery:+pathophysiology,+management,+and+future+directions.">Saphenous vein graft failure after coronary artery bypass surgery: pathophysiology, management, and future directions.</a> Ann Surg. 257, 824-833 (2013).</li><li>Sabik, J. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Understanding+saphenous+vein+graft+patency.">Understanding saphenous vein graft patency.</a> Circulation. 124 (3), 273-275 (2011).</li><li>Owens, C. D., Ho, K. J., Conte, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lower+extremity+vein+graft+failure:+a+translational+approach.">Lower extremity vein graft failure: a translational approach.</a> Vasc Med. 13, 63-74 (2008).</li><li>Robertson, K. E., McDonald, R. A., Oldroyd, K. G., Nicklin, S. A., Baker, A. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prevention+of+coronary+in-stent+restenosis+and+vein+graft+failure:+does+vascular+gene+therapy+have+a+role.">Prevention of coronary in-stent restenosis and vein graft failure: does vascular gene therapy have a role.</a> Pharmacol Ther. 136, 23-34 (2012).</li><li>Yla-Herttuala, S., Baker, A. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiovascular+Gene+Therapy:+Past,+Present,+and+Future.">Cardiovascular Gene Therapy: Past, Present, and Future.</a> Mol Ther. 25, 1095-1106 (2017).</li><li>Schwartz, L. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adenoviral-mediated+gene+transfer+of+a+constitutively+active+form+of+the+retinoblastoma+gene+product+attenuates+neointimal+thickening+in+experimental+vein+grafts.">Adenoviral-mediated gene transfer of a constitutively active form of the retinoblastoma gene product attenuates neointimal thickening in experimental vein grafts.</a> J Vasc Surg. (5), 874-881 (1999).</li><li>Eefting, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+lentiviral+short+hairpin+RNA+silencing+of+CCR2+inhibits+vein+graft+thickening+in+hypercholesterolemic+apolipoprotein+E3-Leiden+mice.">Local lentiviral short hairpin RNA silencing of CCR2 inhibits vein graft thickening in hypercholesterolemic apolipoprotein E3-Leiden mice.</a> J Vasc Surg. 50, 152-160 (2009).</li><li>Handa, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adventitial+delivery+of+platelet-derived+endothelial+cell+growth+factor+gene+prevented+intimal+hyperplasia+of+vein+graft.">Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft.</a> J Vasc Surg. 48 (6), 1566-1574 (2008).</li><li>Kloppenburg, G. T., Grauls, G. E., Bruggeman, C. A., Stassen, F. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adenoviral+activin+A+expression+prevents+vein+graft+intimal+hyperplasia+in+a+rat+model.">Adenoviral activin A expression prevents vein graft intimal hyperplasia in a rat model.</a> Interact Cardiov Th. 8, 31-34 (2009).</li><li>Eefting, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+urokinase+receptor-targeted+inhibitor+for+plasmin+and+matrix+metalloproteinases+suppresses+vein+graft+disease.">A novel urokinase receptor-targeted inhibitor for plasmin and matrix metalloproteinases suppresses vein graft disease.</a> Cardiovasc Res. 88, 367-375 (2010).</li><li>Eichstaedt, H. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gene+transfer+of+COX-1+improves+lumen+size+and+blood+flow+in+carotid+bypass+grafts.">Gene transfer of COX-1 improves lumen size and blood flow in carotid bypass grafts.</a> J Surg Res. 161, 162-167 (2010).</li><li>Kritz, A. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+modulation+of+Nogo-B+attenuates+neointima+formation.">In vivo modulation of Nogo-B attenuates neointima formation.</a> Mol Ther. 16 (11), 1798-1804 (2008).</li><li>Peroulis, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+ex-vivo+gene+therapy+of+vein+grafts+with+Egr-1+decoy+in+the+suppression+of+intimal+hyperplasia.">The role of ex-vivo gene therapy of vein grafts with Egr-1 decoy in the suppression of intimal hyperplasia.</a> Eur J Vasc Endovasc. 40, 216-223 (2010).</li><li>Kochanek, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+adenoviral+vector:+Replacement+of+all+viral+coding+sequences+with+28+kb+of+DNA+independently+expressing+both+full-length+dystrophin+and+b-galactosidase.">A new adenoviral vector: Replacement of all viral coding sequences with 28 kb of DNA independently expressing both full-length dystrophin and b-galactosidase.</a> Proc Natl Acad Sci U S A. 93, 5731-5736 (1996).</li><li>Parks, R. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+helper-dependent+adenovirus+vector+system:+Removal+of+helper+virus+by+Cre-mediated+excision+of+the+viral+packaging+signal.">A helper-dependent adenovirus vector system: Removal of helper virus by Cre-mediated excision of the viral packaging signal.</a> P Natl Acad Sci USA. 93, 13565-13570 (1996).</li><li>Chen, H. -. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Persistence+in+muscle+of+an+adenoviral+vector+that+lacks+all+viral+genes.">Persistence in muscle of an adenoviral vector that lacks all viral genes.</a> P Natl Acad Sci USA. 94, 1645-1650 (1997).</li><li>Wen, S., Graf, S., Massey, P. G., Dichek, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+vascular+gene+transfer+with+a+helper-dependent+adenoviral+vector.">Improved vascular gene transfer with a helper-dependent adenoviral vector.</a> Circulation. 110, 1484-1491 (2004).</li><li>Du, L., Zhang, J., Clowes, A. W., Dichek, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficient+gene+transfer+and+durable+transgene+expression+in+grafted+rabbit+veins.">Efficient gene transfer and durable transgene expression in grafted rabbit veins.</a> Hum Gene Ther. 26, 47-58 (2015).</li><li>Channon, K. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficient+adenoviral+gene+transfer+to+early+venous+bypass+grafts:+comparison+with+native+vessels.">Efficient adenoviral gene transfer to early venous bypass grafts: comparison with native vessels.</a> Cardiovasc Res. 35, 505-513 (1997).</li><li>Flynn, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expression+of+apolipoprotein+A-I+in+rabbit+carotid+endothelium+protects+against+atherosclerosis.">Expression of apolipoprotein A-I in rabbit carotid endothelium protects against atherosclerosis.</a> Mol Ther. 19, 1833-1841 (2011).</li><li>George, S. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sustained+Reduction+of+Vein+Graft+Neointima+Formation+by+Ex+Vivo+TIMP-3+Gene+Therapy.">Sustained Reduction of Vein Graft Neointima Formation by Ex Vivo TIMP-3 Gene Therapy.</a> Circulation. 124, 135-142 (2011).</li><li>Chiu-Pinheiro, C. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gene+transfer+to+coronary+artery+bypass+conduits.">Gene transfer to coronary artery bypass conduits.</a> Ann Thorac Surg. 74, 1161-1166 (2002).</li><li>Byrom, M. J., Bannon, P. G., White, G. H., Ng, M. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+for+the+assessment+of+novel+vascular+conduits.">Animal models for the assessment of novel vascular conduits.</a> J Vasc Surg. 52, 176-195 (2010).</li><li>Ribichini, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+oral+prednisone+after+stenting+in+a+rabbit+model+of+established+atherosclerosis.">Effects of oral prednisone after stenting in a rabbit model of established atherosclerosis.</a> J Am Coll Cardiol. 50, 176-185 (2007).</li><li>Langheinrich, A. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantification+of+in-stent+restenosis+parameters+in+rabbits+by+Micro-CT.">Quantification of in-stent restenosis parameters in rabbits by Micro-CT.</a> Rofo. 177 (4), 501-506 (2005).</li><li>Wacker, B. K., Dronadula, N., Zhang, J., Dichek, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+Vascular+Gene+Therapy+With+Apolipoprotein+A-I+to+Promote+Regression+of+Atherosclerosis.">Local Vascular Gene Therapy With Apolipoprotein A-I to Promote Regression of Atherosclerosis.</a> Arterioscler Thromb. 37, 316-327 (2017).</li><li>Zwolak, R. M., Kirkman, T. R., Clowes, A. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Atherosclerosis+in+rabbit+vein+grafts.">Atherosclerosis in rabbit vein grafts.</a> Arteriosclerosis. 9, 374-379 (1989).</li><li>Qiang, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Statin+therapy+prevents+expansive+remodeling+in+venous+bypass+grafts.">Statin therapy prevents expansive remodeling in venous bypass grafts.</a> Atherosclerosis. 223, 106-113 (2012).</li><li>Casa, L. D. C., Ku, D. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thrombus+Formation+at+High+Shear+Rates.">Thrombus Formation at High Shear Rates.</a> Annu Rev Biomed Eng. 19, 415-433 (2017).</li><li>Chen, C., Coyle, K. A., Hughes, J. D., Lumsden, A. B., Ku, D. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduced+blood+flow+accelerates+intimal+hyperplasia+in+endarterectomized+canine+arteries.">Reduced blood flow accelerates intimal hyperplasia in endarterectomized canine arteries.</a> Cardiovasc Surg. 5 (2), 161-168 (1997).</li><li>Binns, R. L., Ku, D. N., Stewart, M. T., Ansley, J. P., Coyle, K. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimal+graft+diameter:+effect+of+wall+shear+stress+on+vascular+healing.">Optimal graft diameter: effect of wall shear stress on vascular healing.</a> J Vasc Surg. 10, 326-337 (1989).</li><li>Oka, K., Mullins, C. E., Kushwaha, R. S., Leen, A. M., Chan, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gene+therapy+for+rhesus+monkeys+heterozygous+for+LDL+receptor+deficiency+by+balloon+catheter+hepatic+delivery+of+helper-dependent+adenoviral+vector.">Gene therapy for rhesus monkeys heterozygous for LDL receptor deficiency by balloon catheter hepatic delivery of helper-dependent adenoviral vector.</a> Gene Ther. 22, 87-95 (2015).</li><li>Miyake, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prevention+of+neointimal+formation+after+angioplasty+using+nuclear+factor-kappaB+decoy+oligodeoxynucleotide-coated+balloon+catheter+in+rabbit+model.">Prevention of neointimal formation after angioplasty using nuclear factor-kappaB decoy oligodeoxynucleotide-coated balloon catheter in rabbit model.</a> Circ Cardiovasc Interv. 7, 787-796 (2014).</li><li>Chorny, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Site-specific+gene+delivery+to+stented+arteries+using+magnetically+guided+zinc+oleate-based+nanoparticles+loaded+with+adenoviral+vectors.">Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors.</a> FASEB J. 27, 2198-2206 (2013).</li><li>Hoshino, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Three+catheter-based+strategies+for+cardiac+delivery+of+therapeutic+gelatin+microspheres.">Three catheter-based strategies for cardiac delivery of therapeutic gelatin microspheres.</a> Gene Ther. 13, 1320-1327 (2006).</li><li>Nouri, F., Sadeghpour, H., Heidari, R., Dehshahri, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparation,+characterization,+and+transfection+efficiency+of+low+molecular+weight+polyethylenimine-based+nanoparticles+for+delivery+of+the+plasmid+encoding+CD200+gene.">Preparation, characterization, and transfection efficiency of low molecular weight polyethylenimine-based nanoparticles for delivery of the plasmid encoding CD200 gene.</a> Int J Nanomed. , 5557-5569 (2017).</li><li>Jia, S. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Eradication+of+osteosarcoma+lung+metastases+following+intranasal+interleukin-12+gene+therapy+using+a+nonviral+polyethylenimine+vector.">Eradication of osteosarcoma lung metastases following intranasal interleukin-12 gene therapy using a nonviral polyethylenimine vector.</a> Cancer Gene Ther. , 260-266 (2002).</li><li>Morishita, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intimal+hyperplasia+after+vascular+injury+is+inhibited+by+antisense+cdk+2+kinase+oligonucleotides.">Intimal hyperplasia after vascular injury is inhibited by antisense cdk 2 kinase oligonucleotides.</a> J Clin Invest. 93, 1458-1464 (1994).</li></ol>

저자는 공개 없다.

이 프로토콜의 중요 한 단계에는 마 취 관리, anticoagulation, 외과 동맥/투입 정 맥의 조작과 이식할된 정 맥의 hemodynamic 측정 포함 됩니다. 마 취의 적절 한 관리는 포함 하는 두 개의 비교적 긴 작업 (일반적으로 3-3.5 h 양자 정 맥 접목 및 양측 이식 변환에 대 한 1.5-2.5 h)이 여러 생존 수술 모델에에서 중요 한. 우리 마 취는 nosecone 통해 고 endotracheal 삽 관 법에 의해 관리 하 고는 삽 관 법 가능성이 긍정...

동맥 경화는 지질 축적과 혈관 벽에 염증 배 루멘, 심장 마비, 뇌졸중, 및 사지1,2의 손실의 축소로 이어질 만성 염증 성 질병 이다. 경 피 적인 내정간섭 (예., 혈관 및 stenting) 및 의료 치료 (예., 스타 틴과 항 에이전트) 아 테 롬;에 대 한 유용한 치료법 그러나, 그들은 하지 종종 관상동맥 및 말 초 순환에 모두 심각한 폐쇄성 질환 치료에 효과적입니다. 우회 접목, 자생 정 맥 세그먼트를 사용 하 여 심각한, 확산 관상 동맥 및 주변 혈관 질병3,4환자 치료에 대 한 일반적인 절차 남아 있다. 그러나, 모두는 관상에 이식 정 맥 그리고 주변 순환 가난한 장기 patency 요금. 관상 동맥 순환에 있는 정 맥 이식 1 년 50%에서 가려진는의 대략 10-20%는 10 년5,6에 의해 가려진. 주변 순환에서 정 맥 이식 실패 속도 5 년7에서 30-50%.
그것은 질병의 위치에 정확 하 게 치료 유전자 제품을 제공할 수 있기 때문에 유전자 치료는 정 맥 이식 실패의 예방에 대 한 매력적인 접근 이다. 따라서, 수많은 임상 연구는 정 맥 이식 유전자 치료8,9을 테스트 하 고 있다. 그러나, 기본적으로 초기 시간 포인트 (2-12 주)10,11,12,13,,1415, 에서 효능을 조사는 이러한 연구의 모든 16 , 17. 우리는 유전자 치료 개입 내구성 제공할 수 있다는 증거가 인식 (년) 일반적으로 neointimal 증식 및 동맥 경화4결과인 늦은 정 맥 이식 실패에 대 한 보호. 우리 이식할된 혈관에 튼튼한 transgene 식이 허용 함으로써 초기 뿐 아니라 늦은 시간 지점에서 유전자 치료 개입의 테스트 방법을 개발. 튼튼한 transgene 식을 위해 메서드 HDAd 벡터 지연된 변환 전략을 통합. HDAd 벡터 바이러스 성 유전자, 면역 시스템18,19,에 의해 불리고 셀의 인식 (및 제거)20, 를 방지 부족 하기 때문에 장기간된 transgene 식을 제공 21. 지연 변환 (이식 배치 후 수행된 28 일) 일찍22이식 후 발생 하는 arterialization 과정 불리고 세포의 손실 방지.
이식 배치10,,1112,15,16 시 정 맥 이식의 변환에 의존 하는 정 맥 이식 벽에 치료 transgene 식을 달성 하는 다른 방법 ,17. 연속적으로 측정 하는 경우 변환22,23후 transgene 식이이 접근을 사용 하 여 신속 하 게 거절 합니다. 따라서, 학문이 접근이 방식을 사용 하는 하지는 정 맥 접목, 가장 안 4 주 넘어 효능 평가 함께 후 12 주 이상의 효능을 시험 했다. 반면에, 우리의 방법은 정 맥 이식 달성 및 기반 비슷한 연구에서 동맥 가능성이 수행에 24 주 이상 안정적으로 지속 되는 transgene 식 계속 훨씬 더22,24. 우리는 다른 정 맥 이식 유전자 치료 개입 안정적인 transgene 표현의이 기간을 달성 하는 알고 있습니다.
우리는 우리의 방법을 개발 하는 토끼 모델을 사용. 정 맥을 테스트 하려면 큰 동물 이식 유전자 치료10,11,12,15,,1617,25, 또는 다른 사람 설치류, 토끼, 사용 26. 설치류 모델에 비해, 토끼는 더 비싼 하 고는 더 엄격한 규제 요건이 적용 됩니다. 그러나, 더 큰 동물에 비해 (예. 돼지, 개), 토끼는 구입 하 고 집까지 저렴 하 고 훨씬 쉽게 처리할. 또한, 토끼 배 순수 인간의 배를 닮은27, 그들은 충분히 큰 경 피 적인 내정간섭28,29, 테스트를 위해 사용할 수 있습니다 그리고 그들은 충분 한 조직을 제공 여러 끝점 (예., 조직학, 단백질, RNA) 단일 혈관 표본22,30을 사용 하 여 시험 될 수 있다. 또한, 먹 일 때 정 맥 이식 된 토끼는 높은 지방 다이어트와 함께, 그들은 개발 정 맥 이식 동맥 경화31,32, 관상 동맥 바이패스 정 맥 이식 실패4,5의 일반적인 원인입니다. . 이러한 동맥 경 화성 토끼 정 맥 이식이이 방법으로 전달 하는 유전자 치료 개입을 테스트 하기 위한 기판으로 사용할 수 있습니다. 제공 된 프로토콜 토끼 정 맥 이식에 튼튼한 transgene 식을 달성 하는 데 필요한 기술을 마스터 하는 수사를 도울 수 있다.

<table><tbody><tr><td>&lt;strong&gt;Disposables&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>3mL syringe with 24G needle</td><td>Becton Dickinson</td><td>309571</td><td>2x for vein graft surgery; 2x for gene transfer&amp;nbsp; surgery</td></tr><tr><td>1 mL syringe with 27G needle</td><td>Becton Dickinson</td><td>309623</td><td>2x for vein graft surgery, 5x for gene transfer surgery</td></tr><tr><td>19G needle</td><td>Becton Dickinson</td><td>305187</td><td>Gene transfer surgery</td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>20 mL syringe, luer lock</td><td>Nipro Medical Corp</td><td>JD+20L</td><td></td></tr><tr><td>Catheters, 24Ga x 3/4&amp;rdquo;</td><td>Terumo Medical Products</td><td>SROX2419V</td><td></td></tr><tr><td>21G needle</td><td>Becton Dickinson</td><td>305165</td><td>Gene transfer surgery and for 20 mL syringe of saline</td></tr><tr><td>Gauze 4&amp;rdquo; x 4&amp;rdquo;</td><td>Dynarex</td><td>3242</td><td>~10-15 per surgery</td></tr><tr><td>3-0 silk suture</td><td>Covidien Ltd.</td><td>S-244</td><td></td></tr><tr><td>5-0 silk suture</td><td>Covidien Ltd.</td><td>S-182</td><td></td></tr><tr><td>7-0 polypropylene suture</td><td>CP Medical</td><td>8703P</td><td>Vein graft surgery</td></tr><tr><td>7-0 polypropylene suture</td><td>CP Medical</td><td>8648P</td><td>Gene transfer surgery</td></tr><tr><td>5-0 polyglycolic acid suture</td><td>CP Medical</td><td>421A</td><td></td></tr><tr><td>3-0 polyglycolic acid suture</td><td>CP Medical</td><td>398A</td><td></td></tr><tr><td>Alcohol swabs</td><td>Covidien Ltd.</td><td>6818</td><td>For the placement of I.V. line</td></tr><tr><td>Catheter plug</td><td>Vetoquinol</td><td>411498</td><td></td></tr><tr><td>Ketamine HCl, 100 mg/mL</td><td>Vedco Inc.</td><td>5098916106</td><td></td></tr><tr><td>Xylazine, 100 mg/mL</td><td>Akorn Inc.</td><td>4821</td><td></td></tr><tr><td>Lidocaine, 20 mg/mL</td><td>Pfizer</td><td>409427702</td><td></td></tr><tr><td>Marcaine 0.5%</td><td>Pfizer</td><td>409161050</td><td></td></tr><tr><td>Beuthanasia D-Special</td><td>Intervet Inc.</td><td>NDC 00061047305</td><td>Harvest surgery only</td></tr><tr><td>Buprenorphine HCl, 0.3 mg/mL</td><td>Patterson Veterinary</td><td>12496075705</td><td></td></tr><tr><td>Saline IV bag, 0.9% sodium chloride</td><td>Baxter</td><td>2B1309</td><td></td></tr><tr><td>Heparin&amp;nbsp; (5000 U/mL)</td><td>APP Pharmaceuticals</td><td>NDC 63323-047-10</td><td></td></tr><tr><td>Papaverine (3.5 mg/ml)</td><td>American Reagent Inc.</td><td>NDC 0517-4002-25</td><td>Diluted from 30mg/mL stock; Use 1 mL maximum</td></tr><tr><td>Fentanyl patch, 25 mcg/h</td><td>Apotex Corp.</td><td>NDC 60505-7006-2</td><td></td></tr><tr><td>Isoflurane</td><td>Multiple vendors</td><td>Catalog number not available</td><td></td></tr><tr><td>&amp;nbsp;Viral vector</td><td></td><td></td><td>Gene transfer surgery only</td></tr><tr><td>&lt;strong&gt;Surgical Instruments&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Metzenbaum needle holder 7&quot; straight</td><td>Roboz</td><td>RS-7900</td><td></td></tr><tr><td>Operating scissors 6.5&quot; straight blunt/blunt</td><td>Roboz</td><td>RS-6828</td><td></td></tr><tr><td>Needle holder /w suture scissors</td><td>Miltex</td><td>8-14-IMC</td><td></td></tr><tr><td>Castroviejo scissors</td><td>Roboz</td><td>RS-5658</td><td></td></tr><tr><td>Castroviejo needle holder, 5.75&quot; straight with lock</td><td>Roboz</td><td>RS-6412</td><td></td></tr><tr><td>Stevens scissors 4.25&quot; curved blunt/blunt</td><td>Roboz</td><td>RS-5943</td><td></td></tr><tr><td>Alm retractor 4&quot; 4X4 5mm blunt prongs</td><td>Roboz</td><td>RS-6514</td><td>2x</td></tr><tr><td>Backhaus towel clamp 3.5&quot;</td><td>Roboz</td><td></td><td>4x</td></tr><tr><td>Micro clip setting forceps 4.75&quot;</td><td>Roboz</td><td>RS-6496</td><td></td></tr><tr><td>Micro vascular clips, 11 mm</td><td>Roboz</td><td></td><td></td></tr><tr><td>Surg-I-Loop</td><td>Scanlan International</td><td>1001-81M</td><td>5 cm length</td></tr><tr><td>Bonaccolto forceps, 4&amp;rdquo; (10 cm) long longitudinal serrations, cross serrated tip, 1.2mm tip width</td><td>Roboz</td><td>RS-5210</td><td></td></tr><tr><td>Dumont #3 forceps Inox tip size .17 &amp;times; .10 mm</td><td>Roboz</td><td>RS-5042</td><td></td></tr><tr><td>Graefe forceps, 4&amp;rdquo; (10 cm) long serrated straight, 0.8 mm tip</td><td>Roboz</td><td>RS-5280</td><td></td></tr><tr><td>Halstead mosquito forceps,&amp;nbsp; 5&quot; straight, 1.3 mm tips</td><td>Roboz</td><td>RS-7110</td><td>2x</td></tr><tr><td>Halstead mosquito forceps,&amp;nbsp; 5&quot; curved, 1.3mm tips</td><td>Roboz</td><td>RS-7111</td><td></td></tr><tr><td>Jacobson mosquito forceps 5&quot; curved extra delicate, 0.9 mm tips</td><td>Roboz</td><td>RS-7117</td><td></td></tr><tr><td>Kantrowitz forceps, 7.25&quot; 90 degree delicate, 1.7 mm tips</td><td>Roboz</td><td>RS-7305</td><td></td></tr><tr><td>Tissue forceps 5&quot;, 1X2 teeth, 2 mm tip width</td><td>Roboz</td><td>RS-8162</td><td></td></tr><tr><td>Allis-Baby forceps, 12 cm, 4x5 teeth, 3 mm tip width</td><td>Fine Science Tools</td><td>11092-12</td><td>2x</td></tr><tr><td>Adson forceps, 12 cm, serrated, straight</td><td>Fine Science Tools</td><td>11006-12</td><td></td></tr><tr><td>Veterinary electrosurgery handpiece and electrode</td><td>MACAN Manufacturing</td><td>HPAC-1; R-F11</td><td></td></tr><tr><td>&lt;strong&gt;Surgical Suite Equipment&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Circulating warm water blanket and pump</td><td>Multiple vendors</td><td>Catalog number not available</td><td></td></tr><tr><td>Bair hugger warming unit</td><td>3M</td><td>Model 505</td><td></td></tr><tr><td>IV infusion pump</td><td>Heska</td><td>Vet IV 2.2</td><td></td></tr><tr><td>Isoflurane vaporizer and scavenger</td><td>Multiple vendors</td><td>Catalog number not available</td><td></td></tr><tr><td>Veterinary multi-parameter monitor</td><td>Surgivet</td><td>Surgivet Advisor</td><td></td></tr><tr><td>Veterinary electrosurgery unit</td><td>MACAN Manufacturing</td><td>MV-9</td><td></td></tr><tr><td>Surgical microscope</td><td>D.F. Vasconcellos</td><td>M900</td><td>25X magnification for vein graft surgery; 16X magnification for gene transfer surgery</td></tr></tbody></table>

a rabbit model of durable transgene expression in jugular vein to common carotid artery interposition grafts

정 맥 이식 수술은 폐색 동맥 질환;에 대 한 일반적인 치료 그러나, 장기적인 성공은 이식 실패 혈전 증, 내 증식 및 동맥 경화에 의해 제한 됩니다. 이 문서의 목표는 토끼, 양측 정 맥 개재 이식 배치 다음 시험 튼튼한 transgene 식 달성 유전자 전달 벡터와 이식 하는 방법을 보여 줍니다. 메서드를 사용 하면 정상적인 정 맥 이식 항상성에서 유전자와 단백질 제품의 생물 학적 역할의 조사 수 있습니다. 그것은 또한 transgenes 예정 맥 이식 실패를 막을 수 있는 활동에 대 한 테스트 수 있습니다., 여부는 transgene의 표현 neointimal 성장을 방지, 혈관 염증 감소 또는 토끼에 있는 아 테 롬을 감소 먹이 와 고 지방 다이어트. 초기 생존 수술 하는 동안 왼쪽과 오른쪽 외부 경 정 맥의 세그먼트 excised 고 반전된 엔드-투-사이드 일반적인 경 동맥 중재 이식으로 양측 배치. 두 번째 생존 수술, 28 일 후, 수행 하는 동안 각는 이식 혈관 클립 순환에서 격리 이며 루멘 채워진다 (는 arteriotomy)를 통해 도우미 종속 adenoviral (HDAd) 벡터를 포함 하는 솔루션. 20 민 부 화 후 벡터 솔루션 발음 하 고는 arteriotomy 수리 흐름 복원 됩니다. 혈관 각 실험 프로토콜에 의해 결정 하는 시간 포인트에서 수확. 28 일 간격으로 이식 배치 및 변환 동맥 순환에 정 맥 이식의 적응을 위해 필요 하다. 이 적응 정 맥 이식 불리고 전이나 접목 직후에 발생 하는 transgene 식의 급속 한 손실을 방지 합니다. 메서드는 고유한 이식할된 혈관에 내구성, 안정적인 transgene 식을 달성 하는 능력. 다른 큰 동물 정 맥 이식 모델에 비해, 토끼는 저가 및 쉬운 취급의 이점이 있다. 쥐 나 정 맥 이식 모델에 비해, 토끼 크고 조작에 쉽게 혈관이 풍부한 조직 분석을 위해 제공 하는 있다.

New 연산자의 기술 능력 연산자 실험 데이터를 생성 하려면이 메서드를 사용할 수 있습니다 확인 해야 합니다. New 연산자를 달성 해야 합니다 첫 번째 이정표는 일관 정 맥 이식 patency 초기 정 맥 이식 수술과 이후 지연 변환 수술 후. 이상 90 %patency 각 수술의 바람직한 이며 달성 후. patency 비 접촉 우리가 일반적으로 수술 후 하루 5-7에서 수행 하는 경 피 성 초음파를 사용 하...

Watch this Scientific Journal Video about A Rabbit Model of Durable Transgene Expression in Jugular Vein to Common Carotid Artery Interposition Grafts at JoVE.com

A Rabbit Model of Durable Transgene Expression in Jugular Vein to Common Carotid Artery Interposition Grafts

일반적인 경 동맥 중재 이식 정 맥 경에서에서 튼튼한 Transgene 식의 토끼 모델

이 방법은 토끼에 개재 정 맥 이식의 배치, 이식, 변환 및 내구성 transgene 식의 성과 설명합니다. 이로써 transgenes 이식할된 혈관에 단백질 제품의 생리 및 병 적인 역할 및 정 맥 이식 질병에 대 한 유전자 치료의 테스트의 조사.

Vein graft bypass surgery is a common treatment for occlusive arterial disease; however, long-term success is limited by graft failure due to thrombosis, ...

a-rabbit-model-durable-transgene-expression-jugular-vein-to-common

Research

JoVE Journal

Medicine

10.3K 조회수.  University of Washington School of Medicine. 이 방법은 토끼에 개재 정 맥 이식의 배치, 이식, 변환 및 내구성 transgene 식의 성과 설명합니다. 이로써 transgenes 이식할된 혈관에 단백질 제품의 생리 및 병 적인 역할 및 정 맥 이식 질병에 대 한 유전자 치료의 테스트의 조사.

비디오: A Rabbit Model of Durable Transgene Expression in Jugular Vein to Common Carotid Artery Interposition Grafts

Training a Sophisticated Microsurgical Technique: Interposition of External Jugular Vein Graft in the Common Carotid Artery in Rats

Neointimal hyperplasia is one the primary causes of stenosis in arterialized veins that are of great importance in arterial coronary bypass surgery, in peripheral arterial bypass surgery as well as in arteriovenous fistulas.1-5 The experimental procedure of vein graft interposition in the common carotid artery by using the cuff-technique has been applied in several research projects to examine the aetiology of neointimal hyperplasia and therapeutic options to address it. 6-8 The cuff prevents vessel anastomotic remodeling and induces turbulence within the graft and thereby the development of neointimal hyperplasia.
Using the superior caval vein graft is an established small-animal model for venous arterialization experiment.9-11 This current protocol refers to an established jugular vein graft interposition technique first described by Zou et al., 9 as well as others.12-14 Nevertheless, these cited small animal protocols are complicated.
To simplify the procedure and to minimize the number of experimental animals needed, a detailed operation protocol by video training is presented. This video should help the novice surgeon to learn both the cuff-technique and the vein graft interposition. Hereby, the right external jugular vein was grafted in cuff-technique in the common carotid artery of 21 female Sprague Dawley rats categorized in three equal groups that were sacrificed on day 21, 42 and 84, respectively. Notably, no donor animals were needed, because auto-transplantations were performed. The survival rate was 100 % at the time point of sacrifice. In addition, the graft patency rate was 60 % for the first 10 operated animals and 82 % for the remaining 11 animals. The blood flow at the time of sacrifice was 8&plusmn;3 ml/min. In conclusion, this surgical protocol considerably simplifies, optimizes and standardizes this complicated procedure. It gives novice surgeons easy, step-by-step instruction, explaining possible pitfalls, thereby helping them to gain expertise fast and avoid useless sacrifice of experimental animals.

Neointimal hyperplasia is the primary cause of stenosis in arterialized veins. We propose a new protocol whereby the right external jugular vein is grafted using the cuff technique in the common carotid artery of Sprague Dawley rats. The survival rate was 100 % at the time point of sacrifice.

쥐 온목 동맥에 개재 외부 경정맥 정맥 이식의 : 정교한 Microsurgical 기술을 교육

Neointimal hyperplasia is one the primary causes of stenosis in arterialized veins that are of great importance in arterial coronary bypass surgery, in ...

연구

의학

Murine Cervical Heart Transplantation Model Using a Modified Cuff Technique

Mouse models are of special interest in research since a wide variety of monoclonal antibodies and commercially defined inbred and knockout strains are available to perform mechanistic in vivo studies. While heart transplantation models using a suture technique were first successfully developed in rats, the translation into an equally widespread used murine equivalent was never achieved due the technical complexity of the microsurgical procedure. In contrast, non-suture cuff techniques, also developed initially in rats, were successfully adapted for use in mice1-3. This technique for revascularization involves two major steps I) everting the recipient vessel over a polyethylene cuff; II) pulling the donor vessel over the formerly everted recipient vessel and holding it in place with a circumferential tie. This ensures a continuity of the endothelial layer, short operating time and very high patency rates4.
Using this technique for vascular anastomosis we performed more than 1,000 cervical heart transplants with an overall success rate of 95%. For arterial inflow the common carotid artery and the proximal aortic arch were anastomosed resulting in a retrograde perfusion of the transplanted heart. For venous drainage the pulmonary artery of the graft was anastomosed with the external jugular vein of the recipient5.
Herein, we provide additional details of this technique to supplement the video.

The murine cervical heart transplantation model is well suited for immunological as well as ischemia reperfusion injury studies. We modified the procedure using a non-suture cuff technique and performed more than 1,000 successful transplants with this approach.
Herein, we provide additional details of this technique to supplement the video.

수정 커프 기술을 사용하여 쥐의 자궁 심장 이식 모델

Mouse models are of special interest in research since a wide variety of monoclonal antibodies and commercially defined inbred and knockout strains are ...

Heterotopic Cervical Heart Transplantation in Mice

The heterotopic cervical heart transplantation in mice is a valuable tool in transplant and cardiovascular research. The cuff technique greatly simplifies this model by avoiding challenging suture anastomoses of small vessels thereby reducing warm ischemia time. In comparison to abdominal graft implantation the cervical model is less invasive and the implanted graft is easily accessible for further follow-up examinations. Anastomoses are performed by pulling the ascending aorta of the graft over the cuff with the recipient&#8217;s common carotid artery and by pulling the main pulmonary artery over the cuff with the external jugular vein. Selection of appropriate cuff size and complete mobilization of the vessels are important for successful revascularization. Ischemia-reperfusion (I/R) injury can be minimized by perfusing the graft with a cardioplegic solution and by hypothermia. In this article, we provide technical details for a simplified and improved cuff technique, which should allow surgeons with basic microsurgical skills to perform the procedure with a high success rate.

The cuff technique shortens and facilitates the model of heterotopic cervical heart transplantation in mice by avoiding technically challenging suture anastomoses of small vessels. The technical details shown in this video paper should allow researches to establish this model in their laboratories.

마우스의 이소성 자궁 심장 이식

The heterotopic cervical heart transplantation in mice is a valuable tool in transplant and cardiovascular research. The cuff technique greatly simplifies ...

Vein Interposition Model: A Suitable Model to Study Bypass Graft Patency

Bypass grafting is an established treatment method for coronary artery disease. Graft patency continues to be the Achilles heel of saphenous vein grafts. Research models for bypass graft failure are essential for a better understanding of pathobiological and pathophysiological processes during graft patency loss. Large animal models, such as pigs or sheep, resemble human anatomical structures but require special facilities and equipment. This video describes a rat vein interposition model to investigate vein graft patency loss. Rats are inexpensive and easy to handle. Compared to mouse models, the convenient size of rats permits better operability and enables a sufficient amount of material to be obtained for further diverse analysis. In brief, the inferior epigastric vein of a donor rat is harvested and used to replace a segment of the femoral artery. Anastomosis is conducted via single stitches and sealed with fibrin glue. Graft patency can be monitored non-invasively using duplex sonography. Myointimal hyperplasia, which is the main cause for graft patency loss, develops progressively over time and can be calculated from histological cross sections.

This video demonstrates a model to study the development of myointimal hyperplasia after venous interposition surgery in rats.

정맥 삽입 위치 모델 : 바이 패스 이식 개통을 연구하기위한 적절한 모델

Bypass grafting is an established treatment method for coronary artery disease. Graft patency continues to be the Achilles heel of saphenous vein grafts. ...

In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium

The goal of this method is to introduce a transgene into the endothelium of isolated segments of both rabbit common carotid arteries. The method achieves focal endothelial-selective transgenesis, thereby allowing an investigator to determine the biological roles of endothelial-expressed transgenes and to quantify the in vivo transcriptional activity of DNA sequences in large artery endothelial cells. The method uses surgical isolation of rabbit common carotid arteries and an arteriotomy to deliver a transgene-expressing viral vector into the arterial lumen. A short incubation period of the vector in the lumen, with subsequent aspiration of the lumen contents, is sufficient to achieve efficient and durable expression of the transgene in the endothelium, with no detectable transduction or expression outside of the isolated arterial segment. The method allows assessment of the biological activities of transgene products both in normal arteries and in models of human vascular disease, while avoiding systemic effects that could be caused either by targeting gene delivery to other sites (e.g. the liver) or by the alternative approach of delivering genetic constructs to the endothelium by germ line transgenesis. Application of the method is limited by the need for a skilled surgeon and anesthetist, a well-equipped operating room, the costs of purchasing and housing rabbits, and the need for expertise in gene-transfer vector construction and use. Results obtained with this method include: transgene-related alterations in arterial structure, cellularity, extracellular matrix, or vasomotor function; increases or reductions in arterial inflammation; alterations in vascular cell apoptosis; and progression, retardation, or regression of diseases such as intimal hyperplasia or atherosclerosis. The method also allows measurement of the ability of native and synthetic DNA regulatory sequences to alter transgene expression in endothelial cells, providing results that include: levels of transgene mRNA, levels of transgene protein, and levels of transgene enzymatic activity.

In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium

This method is to introduce a transgene into the endothelium of rabbit carotid arteries. Introduction of the transgene allows the assessment of the biological role of the transgene product either in normal arteries or disease models. The method is also useful for measuring activity of DNA regulatory sequences.

Vivo에서 토끼 일반적인 경 동맥 내 피에 유전자 이동

The goal of this method is to introduce a transgene into the endothelium of isolated segments of both rabbit common carotid arteries. The method achieves ...

Murine Cervical Aortic Transplantation Model using a Modified Non-Suture Cuff Technique

With the introduction of powerful immunosuppressive protocols, distinct advances are possible in the prevention and therapy of acute rejection episodes. However, only minor improvement in the long-term results of transplanted solid organs could be observed over the past decades. In this context, chronic allograft vasculopathy (CAV) still represents the leading cause of late organ failure in cardiac, renal and pulmonary transplantation.
Thus far, the underlying pathogenesis of CAV development remains unclear, explaining why effective treatment strategies are presently missing and emphasizing a need for relevant experimental models in order to study the underlying pathophysiology leading to CAV formation. The following protocol describes a murine heterotopic cervical aortic transplantation model using a modified non-suture cuff technique. In this technique, a segment of the thoracic aorta is interpositioned in the right common carotid artery. With the use of the non-suture cuff technique, an easy to learn and reproducible model can be established, minimizing the possible heterogeneity of sutured vascular micro anastomoses.

Here, we present a protocol of heterotopic aortic transplantation in mice using the non-suture cuff technique in a cervical murine model. This model can be used to study the underlying pathology of chronic allograft vasculopathy (CAV) and can help evaluate new therapeutic agents in order to prevent its formation.

수정된 비봉합사 커프 기술을 사용한 뮤린 자궁 경부 대동맥 이식 모델

With the introduction of powerful immunosuppressive protocols, distinct advances are possible in the prevention and therapy of acute rejection episodes. ...

A Rabbit Venous Interposition Model Mimicking Revascularization Surgery using Vein Grafts to Assess Intimal Hyperplasia under Arterial Blood Pressure

Although vein grafts have been commonly used as autologous grafts in revascularization surgeries for ischemic diseases, the long-term patency remains poor because of the acceleration of intimal hyperplasia due to the exposure to arterial blood pressure. The present protocol is designed for the establishment of experimental venous intimal hyperplasia by interposing rabbit jugular veins to the ipsilateral carotid arteries. The protocol does not require surgical procedures deep in the body trunk and the extent of the incision is limited, which is less invasive for the animals, allowing long-term observation after implantation. This simple procedure enables researchers to investigate strategies to attenuate the progression of intimal hyperplasia of the implanted vein grafts. Using this protocol, we reported the effects transduction of microRNA-145 (miR-145), which is known to control the phenotype of vascular smooth muscle cells (VSMCs) from the proliferative to the contractile state, into harvested vein grafts. We confirmed the attenuation of intimal hyperplasia of vein grafts by transducing miR-145 before implantation surgery through the phenotype change of the VSMCs. Here we report a less invasive experimental platform to investigate the strategies that can be used to attenuate intimal hyperplasia of vein grafts in revascularization surgeries.

The present protocol aims to experimentally create venous intimal hyperplasia by subjecting veins to arterial blood pressure for developing strategies to attenuate venous intimal hyperplasia following revascularization surgery using vein grafts.

정맥 이식편을 사용하여 동맥 혈압하에서 인티맥 증식을 평가하는 재혈관 외과를 모방한 토끼 정맥 중개 모델

Although vein grafts have been commonly used as autologous grafts in revascularization surgeries for ischemic diseases, the long-term patency remains poor ...

Implantation of Tissue-Engineered Vascular Graft in Mouse Carotid Artery via Cuff Technique

The development of small-diameter vascular grafts has been a global endeavor, with numerous research groups contributing to this field. Animal experimentation plays a pivotal role in assessing the efficacy and safety of vascular grafts, particularly in the absence of clinical applications. Compared to alternative animal models, the mouse implantation model offers several advantages, including a well-defined genetic background, a mature method for disease model construction, and a straightforward surgical procedure. Based on these advantages, the present study devised a simple cuff technique for the implantation of tissue-engineered vascular grafts in the mouse carotid artery. This technique began with the fabrication of polycaprolactone (PCL) small-diameter vascular grafts via electrostatic spinning, followed by the seeding of macrophages onto the grafts through perfusion adsorption. Subsequently,&#160;the cellularized tissue-engineered vascular grafts were transplanted into the mouse carotid artery using the cuff technique to evaluate patency and regenerative capability. After 30 days of in vivo implantation, vascular patency was found to be satisfactory, with evidence of neo-tissue regeneration and the formation of an endothelial layer within the lumen of the grafts. All data were analyzed using statistical and graphing software. This study successfully established a mouse carotid artery implantation model that can be used to explore the cellular sources of vascular regeneration and the mechanisms of action of active substances. Furthermore, it provides theoretical support for the development of novel small-diameter vascular grafts.

Here, a protocol is presented for the implantation of a tissue-engineered vascular graft into the mouse carotid artery using the cuff technique, providing a suitable animal model for investigating vascular tissue regeneration mechanisms.

커프 기법을 통한 마우스 경동맥에 조직 공학 혈관 이식편 이식

The development of small-diameter vascular grafts has been a global endeavor, with numerous research groups contributing to this field. Animal ...

생체공학

A Simplified Model for Heterotopic Heart Valve Transplantation in Rodents

There is an urgent clinical need for heart valve replacements that can grow in children. Heart valve transplantation is proposed as a new type of transplant with the potential to deliver durable heart valves capable of somatic growth with no requirement for anticoagulation. However, the immunobiology of heart valve transplants remains unexplored, highlighting the need for animal models to study this new type of transplant. Previous rat models for heterotopic aortic valve transplantation into the abdominal aorta have been described, though they are technically challenging and costly. For addressing this challenge, a renal subcapsular transplant model was developed in rodents as a practical and more straightforward method for studying heart valve transplant immunobiology. In this model, a single aortic valve leaflet is harvested and inserted into the renal subcapsular space. The kidney is easily accessible, and the transplanted tissue is securely contained in a subcapsular space that is well vascularized and can accommodate a variety of tissue sizes. Furthermore, because a single rat can provide three donor aortic leaflets and a single kidney can provide multiple sites for transplanted tissue, fewer rats are required for a given study. Here, the transplantation technique is described, providing a significant step forward in studying the transplant immunology of heart valve transplantation.

This protocol describes a simple and efficient method for the transplantation of aortic valve leaflets under the renal capsule to allow for the study of alloreactivity of heart valves.

설치류의 이종 주제 심장 판막 이식을위한 단순화 된 모델

There is an urgent clinical need for heart valve replacements that can grow in children. Heart valve transplantation is proposed as a new type of ...

Jugular Vein Graft Harvest From a Rabbit Model: A Surgical Procedure to Excise a Segment of Rabbit Jugular Vein for Ex Vivo Studies

Source: Nishio, H., et al. <a href="https://www.jove.com/v/60931">A Rabbit Venous Interposition Model Mimicking Revascularization Surgery using Vein Grafts to Assess Intimal Hyperplasia under Arterial Blood Pressure</a> J. Vis. Exp. (2020).
In this video, we demonstrate a procedure for surgically harvesting a segment of the jugular vein from a rabbit model. The resected segment can be used as an autologous vein graft to study intimal hyperplasia that develops due to arterial blood pressure.

토끼 모델에서 경정맥 이식 수확: 생체 외 연구를 위해 토끼 경정맥 부분을 절제하는 수술 절차

Source: Nishio, H., et al. A Rabbit Venous Interposition Model Mimicking Revascularization Surgery using Vein Grafts to Assess Intimal Hyperplasia under ...