Name: mouse kidney transplantation: models of allograft rejection
Uploaded: 2014-10-11T15:00:00
Description: Watch this Scientific Journal Video about Mouse Kidney Transplantation: Models of Allograft Rejection at JoVE.com

Finansiering fra Kidney Research Storbritannia, The Royal College of Surgeons i Edinburgh og The European Society for organtransplantasjon støttet denne studien.

Egnede nasjonale og lokale institusjonelle etikk bør være på plass før du utfører dyreforsøk. Spesielt i Storbritannia de følgende forsøk ble foretatt under Dyr (vitenskapelige prosedyrer) Act 1986 Hvor to microsurgeons er tilgjengelig for å operere samtidig giver kirurg skal utføre trinn 1,1 til 1,16 og deretter 3,1 til 3,5, mens mottakeren kirurgen utfører 2.1-2.8 . For en enkelt operatør fremgangsmåten kan følges sekvensielt. 1. Donor Forberedelse ...

<ol>
	<li>Guild, W. R., Harrison, J. H., Merrill, J. P., Murray, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Successful+homotransplantation+of+the+kidney+in+an+identical+twin.">Successful homotransplantation of the kidney in an identical twin.</a> Trans. Am. Clin. Climatol Assoc. 67, 167-173 (1955).</li><li>Wolfe, R. A., 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+mortality+in+all+patients+on+dialysis,+patients+on+dialysis+awaiting+transplantation,+and+recipients+of+a+first+cadaveric+transplant.">Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.</a> N. Engl. J. Med. 341, 1725-1730 (1999).</li><li>Nankivell, B. J., Alexander, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Rejection of the Kidney Allograft. N. Engl. J. Med. 363, 1451-1462 (2010).</li><li>Tse, G. H., Hughes, J., Marson, L. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systematic+review+of+mouse+kidney+transplantation.">Systematic review of mouse kidney transplantation.</a> Transplant International. 26, 1149-1160 (2013).</li><li>Skoskiewicz, M., Chase, C., Winn, H. J., Russell, P. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kidney+transplants+between+mice+of+graded+immunogenetic+diversity.+Transplant.">Kidney transplants between mice of graded immunogenetic diversity. Transplant.</a> Proc. 5, 721-725 (1973).</li><li>Zhang, Z., 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=Pattern+of+liver,+kidney,+heart,+and+intestine+allograft+rejection+in+different+mouse+strain+combinations.">Pattern of liver, kidney, heart, and intestine allograft rejection in different mouse strain combinations.</a> Transplantation. 62, 1267-1272 (1996).</li><li>Qi, 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=Depletion+of+cells+of+monocyte+lineage+prevents+loss+of+renal+microvasculature+in+murine+kidney+transplantation.">Depletion of cells of monocyte lineage prevents loss of renal microvasculature in murine kidney transplantation.</a> Transplantation. 86, 1267-1274 (2008).</li><li>Dang, Z., Mackinnon, A., Marson, L. P., Sethi, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tubular+atrophy+and+interstitial+fibrosis+after+renal+transplantation+is+dependent+on+galectin-3.">Tubular atrophy and interstitial fibrosis after renal transplantation is dependent on galectin-3.</a> Transplantation. 93, 477-484 (2012).</li><li>Jabs, W. 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=Heterogeneity+in+the+Evolution+and+Mechanisms+of+the+Lesions+of+Kidney+Allograft+Rejection+in+Mice.">Heterogeneity in the Evolution and Mechanisms of the Lesions of Kidney Allograft Rejection in Mice.</a> Am. J. Transplant. 3, 1501-1509 (2003).</li><li>Lin, 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=Deficiency+of+C4+from+Donor+or+Recipient+Mouse+Fails+to+Prevent+Renal+Allograft+Rejection.">Deficiency of C4 from Donor or Recipient Mouse Fails to Prevent Renal Allograft Rejection.</a> Am. J. Pathol. 168, 1241-1248 (2006).</li></ol>

Den mest beskrevne måte for å utføre den arterielle anastomose er å bruke den distale aorta av donor, med den renale arterie i forlengelse, i en ende-til-side-måte til mottakeren aorta. Vi beskriver bruk av en aorta patch, ligner på &#39;Carrell patch&#39; speiling som utføres i menneskelig nyretransplantasjon som vi mener er mer praktisk. Selv om rapporter i litteraturen av giver og mottaker operative tid er sparsom tror vi at å benytte en aortic patch til mottaker aorta i stedet for ende-til-side donor aorta t...

Vellykket nyretransplantasjon for behandling av nyresvikt ble først beskrevet i 1955 mellom eneggede tvillinger 1, siden da har det blitt en revolusjonerende behandling for pasienter med terminal nyresvikt i hele verden, og tilbyr både forbedring i lengde og livskvalitet to. Men langsiktig graft overlevelse har vært hemmet av en rekke patologiske prosesser som resulterer i kronisk allograft skade tre. Avvisning av transplantert nyre hos mennesker er fortsatt en viktig årsak til sykelighet, til tross for betydelige forbedringer i immunosupporessive regimer. Sikte på å utvikle en musemodell for nyretransplantasjon er å nøye replikere prosessen og patologi funnet i menneskelig nyretransplantasjon fire. Skoskiewicz et al. Først beskrev musemodell for nyretransplantasjon i 1973 fem. Selv avanserte mikrokunnskaper er nødvendig, er det en verdifull tOOL av flere grunner: musen genomet har blitt godt karakterisert og det er et stort utvalg av eksperimentelle metoder og teknikker tilgjengelig for musestudier. Mange grupper ved hjelp av musemodell for nyretransplantasjon har brukt den transplanterte nyre som et livsunderstøttende organ, men i andre studier og i vår beskrevne metodikk en av mottakerens mus har native nyrer er igjen in situ for varigheten av eksperimentet 4. Fordelen er at musen gjennomgår en enkelt anestesi og operasjon og dermed redusere sykelighet til musen og risikoen for å dø av en annen prosedyre. I tillegg musen ikke lider av de negative virkningene av gradvis nyresvikt. Selv om modeller av allogen avvisning eksistere i andre organer som hjerte og hud, disse er ikke alltid direkte relevant for nyretransplantasjon. Det er dokumentert at disse modellene lokke fram ulike moduser og dydynamikk for avvisning, for eksempel den tiden løpet av avvisning i hjerte allograft og renal allograft skiller seg vesentlig i visse belastningskombinasjoner seks. Vi har beskrevet akutte nyre allograft avvisning mønstre i BALB / c givere til ikke-transgene FVB / NJ mus, denne modellen viste cellular mediert skade med opphopning av T-celler og makrofager 7. Alternativt har vi også beskrevet en modell av kronisk allograft skade som viser interstitiell fibrose og tubulær atrofi, dette resulterer fra transplantere en nyre fra C57BL / 6 BM12 givere inn C57BL / 6 mottakere, som disse musene er preget av en enkelt MHC klasse II loci mis -match åtte. Flere aspekter av transplantasjon har blitt studert ved hjelp av musemodell for nyretransplantasjon inkludert akutt avvisning, cellulær og humoral avvisning, iskemi reperfusjonsskade, og trialing nye terapeutiske midler. Vi har endret den kirurgiske technique å redusere driftstiden og forbedre den enkle operasjonen. Spesielt har vi beskrevet samtidig giver og mottaker preparatet og en forenklet vaskulær anastomose teknikk ved å benytte en kontinuerlig aorta patch anastomose. Denne videoen og manuskript vil gi viktige poeng til hjelp i etableringen av denne teknikken.

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			<td>Surgical Instruments</td>
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			<td>Blunt Dissecting Scissors</td>
			<td>Fine Science Tools</td>
			<td>&#160;14072-10</td>
			<td>For skin cutting</td>
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			<td>Curved Castoviejo scissors</td>
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			<td>Toothed forceps 1x2 teeth</td>
			<td>Fine Science Tools</td>
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			<td>2 x Fine Tip forceps (Dumont No.5)</td>
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			<td>Angled Fine Tip forceps (Dumont No. 5/45)</td>
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			<td>Curved Fine Tip forcep (Dumont No.7)</td>
			<td>Fine Science Tools</td>
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			<td>Useful to pass around vessels</td>
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			<td>Curved Crile Haemostat</td>
			<td>Fine Science Tools</td>
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			<td>Carl Zeiss</td>
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			<td>Thermal cautery unit with fine tip</td>
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			<td>150A</td>
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			<td>6/O Vicryl (plygalectin)</td>
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			<td>W9537</td>
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			<td>Regular bevel needle, 1 inch, 21G</td>
			<td>Bection, Dickinson and Company</td>
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			<td>Regular bevel needle, 5/8 inch, 25G</td>
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			<td>Regular bevel needle, 1/2 inch, 30G</td>
			<td>Bection, Dickinson and Company</td>
			<td>304000</td>
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			<td>Insulin needle 1ml, 29G</td>
			<td>Bection, Dickinson and Company</td>
			<td>324827</td>
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			<td>Insulin needle 0.3ml, 30G</td>
			<td>Bection, Dickinson and Company</td>
			<td>324826</td>
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			<td>1 ml syringe slip tip</td>
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			<td>5 ml syringe slip tip</td>
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			<td>Dispensing Pin</td>
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			<td>(Lacri-Lube) White soft paraffin 57.3%, mineral oil 42.5% and lanolin alcohols 0.2%</td>
			<td>Allergan Ltd</td>
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			<td>Ecolab Ltd</td>
			<td>PL 04509/0041</td>
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			<td>(Vetalar V) Ketamine hydrochloride</td>
			<td>Pfizer Animal Health</td>
			<td>Vm 42058/4165</td>
			<td>100mg/ml solution (dose 200mg/kg)</td>
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			<td>(Domitor) Medetomidine hydrochloride&#160;</td>
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			<td>Vm 06043/4003</td>
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			<td>University of Wisconsin Solution</td>
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			<td>NaCl 0.9%</td>
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			<td>Heparin Sulphate</td>
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mouse kidney transplantation: models of allograft rejection

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely replicates both the technical and pathological processes that occur in human renal transplantation. Although mouse models of allogeneic rejection in organs other than the kidney exist, and are more technically feasible, there is evidence that different organs elicit disparate rejection modes and dynamics, for instance the time course of rejection in cardiac and renal allograft differs significantly in certain strain combinations. This model is an attractive tool for many reasons despite its technical challenges. As inbred mouse strain haplotypes are well characterized it is possible to choose donor and recipient combinations to model acute allograft rejection by transplanting across MHC class I and II loci. Conversely by transplanting between strains with similar haplotypes a chronic process can be elicited were the allograft kidney develops interstitial fibrosis and tubular atrophy. We have modified the surgical technique to reduce operating time and improve ease of surgery, however a learning curve still needs to be overcome in order to faithfully replicate the model. This study will provide key points in the surgical procedure and aid the process of establishing this technique.

Nedsatt allograft avvisning kan vurderes ved histologisk analyse av methacarn-fast parafininnstøpte vevssnitt av transplantert nyre (figur 2). Isograft transplantasjon av nyrer mellom syngene muse resulterer i nedsatt iskemisk reperfusjonsskade, men etter 4 uker tubuli har gjenvunnet og er histologisk sammenlignes med innfødte nyrer. Akutt avvisning kan modelleres ved C57BL / 6 nyretransplantasjon inn BALB / c mottakere, innen 1 uke er det diffuse mononukleære celleinfiltrasjon gjennom nyreparenchyme...

Watch this Scientific Journal Video about Mouse Kidney Transplantation: Models of Allograft Rejection at JoVE.com

Mouse Kidney Transplantation: Models of Allograft Rejection

Here, we present a protocol to study the immunology of rejection. The surgical model presented reports a short operating time and a concise technique. Depending on the donor-recipient strain combination, the transplanted kidney may develop acute cellular rejection or chronic allograft damage, defined by interstitial fibrosis and tubular atrophy.

Mus nyretransplanterte: Modeller av allograft-avstøting

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely ...

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