orthotopic-aortic-transplantation-rat-model-to-study-development

Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant ...

inducing-myointimal-hyperplasia-versus-atherosclerosis-mice-an

Inducing Myointimal Hyperplasia Versus Atherosclerosis in Mice: An Introduction of Two Valid Models

Various in vivo laboratory rodent models for the induction of artery stenosis have been established to mimic diseases that include arterial plaque ...

University Hospital Hamburg

Cardiovascular Research Center (CVRC) and DZHK University Hamburg

&#x6211;&#x4EEC;&#x8FD9;&#x91CC;&#x4ECE;&#x75C5;&#x4EBA;&#x76EE;&#x524D;&#x4EBA;&#x7C7B;&#x8110;&#x5E26;&#x886C;&#x780C;&#x9AA8;&#x9AD3;&#x95F4;&#x5145;&#x8D28;&#x5E72;&#x7EC6;&#x80DE; &#xFF08;clMSCs&#xFF09; &#x548C;&#x6210;&#x4EBA;&#x9AA8;&#x9AD3; MSCs (bmMSCs) &#x514D;&#x75AB;&#x8089;&#x640F;&#x6218;&#x6BD4;&#x8F83; &gt; 65 &#x5E74;&#x5C81;&#x3002;clMSCs &#x5DF2;&#x7ECF;&#x5927;&#x5927;&#x4F4E;&#x4E8E; HLA I &#x7C7B;&#x8868;&#x8FBE;&#x3001; &#x66F4;&#x9AD8;&#x7684;&#x751F;&#x4EA7;&#x7684;&#x8010;&#x53D7; TGF-&beta; &#x53CA; IL-10 &#x548C;&#x663E;&#x793A;&#x901F;&#x5EA6;&#x5927;&#x5927;&#x52A0;&#x5FEB;&#x6269;&#x6563;&#x3002;&#x540C;&#x79CD;&#x5F02;&#x4F53;&#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x4F53;&#x5916;&#x6D3B;&#x5316;&#x548C;&#x5F02;&#x79CD;&#x4F53;&#x5185;&#x514D;&#x75AB;&#x6FC0;&#x6D3B;&#x662F;&#x5927;&#x5E45;&#x5347;&#x503C;&#x4E0E; bmMSCs&#xFF0C;&#x800C; clMSCs &#x7684;&#x514D;&#x75AB;&#x8BC6;&#x522B;&#x662F;&#x5927;&#x5927;&#x524A;&#x5F31;&#x3002;&#x56E0;&#x6B64;&#xFF0C;bmMSCs &#x66F4;&#x5FEB;&#x5730;&#x5728;&#x514D;&#x75AB;&#x5C0F;&#x9F20;&#x4E2D;&#x62D2;&#x7EDD;&#x4E86;&#x3002;&#x5E72;&#x6270;&#x7D20;-&gamma; &#x5728; 25 ng/ml &#x5747;&#x589E;&#x52A0;&#x514D;&#x75AB;&#x539F;&#x6027;&#x7684; HLA &#x8868;&#x8FBE;&#x4E0A;&#x8C03;&#x4E00;&#x7C7B; / HLA-DR &#x8868;&#x8FBE;&#x548C; tolerogenicity &#x901A;&#x8FC7;&#x589E;&#x52A0;&#x7EC6;&#x80DE; HLA-G &#x548C;&#x8868;&#x9762; HLA-E &#x8868;&#x8FBE;&#xFF0C;&#x5145;&#x5B9E; TGF-&beta; &#x53CA; IL-10 &#x91CA;&#x653E;&#x548C;&#x8BF1;&#x5BFC;&#x5432;&#x54DA;&#x80FA; 2&#xFF0C;3-&#x53CC;&#x52A0;&#x6C27;&#x9176; (&#x4F9D;&#x5F97;) &#x8868;&#x8FBE;&#x3002;&#x6D53;&#x5EA6;&#x66F4;&#x9AD8;&#x7684;&#x5E72;&#x6270;&#x7D20; &gamma; (&gt; 50 ng/ml&#xFF09; &#x8FDB;&#x4E00;&#x6B65;&#x52A0;&#x5F3A;&#x514D;&#x75AB;&#x6291;&#x5236;&#x8868;&#x578B;&#x7684; clMSCs&#x3001; &#x66F4;&#x5F3A;&#x70C8;&#x964D;&#x7CD6; HLA &#x8868;&#x8FBE;&#x548C;&#x8FDB;&#x4E00;&#x6B65;&#x589E;&#x4EA7;&#x4F9D;&#x5F97; (500 ng/ml)&#x3002;MSCs &#x51C0;&#x529F;&#x80FD;&#x514D;&#x75AB;&#x6291;&#x5236;&#x7597;&#x6548;&#x6DF7;&#x5408;&#x7684;&#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x57F9;&#x517B;&#x4E2D;&#x8FDB;&#x884C;&#x4E86;&#x6D4B;&#x8BD5;&#x3002;&#x5C3D;&#x7BA1; clMSCs &#x548C; bmMSCs &#x5927;&#x5927;&#x51CF;&#x5C11;&#x4F53;&#x5916;&#x514D;&#x75AB;&#x6FC0;&#x6D3B;&#xFF0C;clMSCs &#x662F;&#x6BD4; bmMSCs &#x7684;&#x6709;&#x6548;&#x5F97;&#x591A;&#x3002;&#x4E24;&#x4E2A; MSC &#x884C;&#x7684;&#x5426;&#x51B3;&#x6743;&#x529F;&#x80FD;&#x5347;&#x7EA7;&#x5E72;&#x6270;&#x7D20; &gamma; &#x73AF;&#x5883;&#x4E2D;&#x5F97;&#x5230;&#x4E86;&#x589E;&#x5F3A;&#x3002;&#x6700;&#x540E;&#xFF0C;clMSCs &#x663E;&#x793A;&#x914D;&#x7F6E;&#x6587;&#x4EF6; immunogeneic &#x66F4;&#x6709;&#x76CA;&#x548C;&#x66F4;&#x5F3A;&#x7684;&#x6574;&#x4F53;&#x514D;&#x75AB;&#x6291;&#x5236;&#x6F5C;&#x529B;&#x6BD4;&#x5C81; bmMSCs&#x3002;

&#x514D;&#x75AB;&#x539F;&#x6027;&#x548C;&#x514D;&#x75AB;&#x8C03;&#x8282;&#x6027;&#x80FD;&#x7684;&#x8110;&#x7EBF;&#x886C;&#x780C;&#x9AA8;&#x9AD3;&#x95F4;&#x5145;&#x8D28;&#x5E72;&#x7EC6;&#x80DE;&#x3002;

We here present an immunologic head-to-head comparison between human umbilical cord lining mesenchymal stem cells (clMSCs) and adult bone marrow MSCs (bmMSCs) from patients >65 years of age. clMSCs had significantly lower HLA class I expression, higher production of tolerogenic TGF-Î² and IL-10, and showed significantly faster proliferation. In vitro activation of allogeneic lymphocytes and xenogeneic in vivo immune activation was significantly stronger with bmMSCs, whereas immune recognition of clMSCs was significantly weaker. Thus, bmMSCs were more quickly rejected in immunocompetent mice. IFN-Î³ at 25 ng/ml increased both immunogenicity by upregulation of HLA class I/ HLA-DR expression and tolerogenicity by increasing intracellular HLA-G and surface HLA-E expression, augmenting TGF-Î² and IL-10 release, and inducing indoleamine 2,3-dioxygenase (IDO) expression. Higher concentrations of IFN-Î³ (>50 ng/ml) further enhanced the immunosuppressive phenotype of clMSCs, more strongly downregulating HLA-DR expression and further increasing IDO production (at 500 ng/ml). The net functional immunosuppressive efficacy of MSCs was tested in mixed lymphocyte cultures. Although both clMSCs and bmMSCs significantly reduced in vitro immune activation, clMSCs were significantly more effective than bmMSCs. The veto function of both MSC lines was enhanced in escalating IFN-Î³ environments. In conclusion, clMSCs show a more beneficial immunogeneic profile and stronger overall immunosuppressive potential than aged bmMSCs.

Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells.

Nous pr&#xE9;sentons ici une immunologique t&#xEA;te-&#xE0;-t&#xEA;te comparaison entre les cellules du cordon ombilical doublure souches m&#xE9;senchymateuses (clMSCs) et des adultes de moelle osseuse MSC (bmMSCs) provenant de patients de plus de 65 ans. clMSCs &#xE9;tait significativement inf&#xE9;rieure HLA de classe I d&#x26;#39;expression, augmentation de la production de TGF-&#x3B2; tol&#xE9;rog&#xE8;ne et de l&#x26;#39;IL-10, et montrait une prolif&#xE9;ration beaucoup plus rapide. In vitro l&#x26;#39;activation des lymphocytes allog&#xE9;niques et x&#xE9;nog&#xE9;niques dans l&#x26;#39;activation immunitaire in vivo &#xE9;tait significativement plus forte avec bmMSCs, consid&#xE9;rant que la reconnaissance immunitaire de clMSCs &#xE9;tait significativement plus faible. Ainsi, ont &#xE9;t&#xE9; bmMSCs plus rapidement rejet&#xE9;e chez les souris immunocomp&#xE9;tentes. IFN-&#x3B3; &#xE0; 25 ng / ml &#xE0; la fois augment&#xE9; immunog&#xE9;nicit&#xE9; par la r&#xE9;gulation positive de HLA de classe I / HLA-DR expression et tolerogenicity en augmentant intracellulaire de HLA-G et la surface de HLA-E expression, augmentant lib&#xE9;ration du TGF-&#x3B2; et l&#x26;#39;IL-10, et d&#x26;#39;induire indoleamine 2,3-dioxyg&#xE9;nase (IDO) expression. Des concentrations plus &#xE9;lev&#xE9;es d&#x26;#39;IFN-&#x3B3; (&#x26;gt; 50 ng / ml) a rehauss&#xE9; encore le ph&#xE9;notype immunosuppresseur de clMSCs, plus fortement la r&#xE9;gulation n&#xE9;gative de l&#x26;#39;expression HLA-DR et augmenter encore la production IDO (&#xE0; 500 ng / ml). Le filet de l&#x26;#39;efficacit&#xE9; fonctionnelle immunosuppresseur des CSM a &#xE9;t&#xE9; test&#xE9;e dans des cultures de lymphocytes mixtes. Bien que les deux clMSCs et bmMSCs consid&#xE9;rablement r&#xE9;duit in vitro l&#x26;#39;activation immunitaire, clMSCs &#xE9;taient significativement plus efficace que bmMSCs. Le droit de veto des deux lignes du SMC a &#xE9;t&#xE9; renforc&#xE9;e dans l&#x26;#39;escalade des IFN-y les environnements. En conclusion, clMSCs montrent un profil plus avantageux et plus fort immunogeneic potentiel global immunosuppresseur que bmMSCs &#xE2;ge.

Propri&#xE9;t&#xE9;s d&#x26;#39;immunog&#xE9;nicit&#xE9; et immunomodulatrices des cellules de cordon ombilical Doublure souches m&#xE9;senchymateuses

Wir stellen hier eine immunologische Direktvergleich zwischen menschlichen Nabelschnur Futter mesenchymale Stammzellen (ClMSCs) und Erwachsenen Knochenmark MSCs (BmMSCs) von Patienten &gt; 65 Jahre alt. ClMSCs hatte deutlich niedriger HLA Klasse I, Ausdruck, h&ouml;here Produktion von Tolerogenic TGF-&beta; und IL-10 und zeigte deutlich schneller Verbreitung. In-vitro-allogene Lymphozyten und xenogeneic in-vivo-immun-Aktivierung war deutlich st&auml;rker mit BmMSCs, immun Anerkennung der ClMSCs deutlich schw&auml;cher. So wurden BmMSCs bei immunkompetenten M&auml;usen schneller abgelehnt. IFN-&gamma; bei 25 ng/ml erh&ouml;ht sowohl Immunogenit&auml;t durch Hochregulation von HLA Klasse I / HLA-DR-Ausdruck Tolerogenicity durch eine Erh&ouml;hung der intrazellul&auml;ren HLA-G und Oberfl&auml;che HLA-E Ausdruck, eine Verst&auml;rkung der TGF-&beta; und IL-10 Freisetzung und induzierende Indolamin-2, 3-Dioxygenase (IDO) Ausdruck. H&ouml;here Konzentrationen von IFN-&gamma; (&gt; 50 ng/ml) verst&auml;rkt die immunsuppressive Ph&auml;notyp ClMSCs, mehr stark Herunterregulierung HLA-DR Meinungs-und weitere Produktionssteigerung IDO (bei 500 ng/ml). Net funktionale immunsuppressive Wirksamkeit von MSCs wurde in gemischten Lymphozyten Kulturen getestet. Obwohl sowohl die ClMSCs als auch die BmMSCs deutlich in-vitro-immun-Aktivierung reduziert, waren ClMSCs deutlich effektiver als BmMSCs. Die Veto-Funktion der beiden MSC-Linien wurde in eskalierenden IFN-&gamma;-Umgebungen verbessert. Abschlie&szlig;end zeigen ClMSCs, ein g&uuml;nstiger Immunogeneic Profil und st&auml;rkere insgesamt immunsuppressive Potential, als Alter BmMSCs.

Immunogenit&auml;t und immunmodulatorische Eigenschaften der Nabelschnur Schnur Futter mesenchymale Stammzellen.

Presentiamo qui un confronto testa a testa immunologico tra cellule staminali mesenchimali fodera del cordone ombelicale umano (clMSCs) e il midollo osseo adulto MSCs (bmMSCs) da pazienti &amp;gt; 65 anni di et&agrave;. clMSCs era significativamente inferiore HLA di classe I espressione, una maggiore produzione di tollerogeniche TGF-&beta; e IL-10 e ha dimostrato significativamente pi&ugrave; veloce proliferazione. Attivazione in vitro dei linfociti allogenici e xenogenici attivazione immunitaria in vivo era significativamente pi&ugrave; forte con bmMSCs, mentre per riconoscimento immune di clMSCs era significativamente pi&ugrave; debole. Cos&igrave;, bmMSCs pi&ugrave; rapidamente sono state respinte in topi immunitarie. IFN-&gamma; a 25 ng/ml sia aumentato immunogenicit&agrave; di sovraregolazione di HLA di classe I / espressione di HLA-DR tolerogenicity aumentando intracellulare HLA-G e espressione di HLA-E superficie, aumentando il TGF-&beta; e IL-10 rilascio e indurre l&#39;espressione di indoleamine 2,3-diossigenasi (IDO). Concentrazioni pi&ugrave; elevate di IFN-&gamma; (&amp;gt; 50 ng/ml) ulteriormente rafforzato il fenotipo immunosoppressivo di clMSCs, pi&ugrave; fortemente espressione riducono HLA-DR e aumentare ulteriormente la produzione di IDO (a 500 ng/ml). Net efficacia immunosoppressiva funzionale di MSCs &egrave; stato testato in colture linfocitarie miste. Sebbene sia clMSCs che bmMSCs notevolmente ridotta attivazione immunitaria in vitro, clMSCs erano significativamente pi&ugrave; efficace del bmMSCs. La funzione di veto di entrambe le linee di MSC &egrave; stata migliorata in escalation ambienti di IFN-&gamma;. In conclusione, clMSCs mostrano un profilo immunogeneic pi&ugrave; vantaggioso e pi&ugrave; forte potenziale complessivo immunosoppressivi rispetto all&#39;et&agrave; bmMSCs.

Propriet&agrave; immunogenicit&agrave; e immunomodulatori di ombelicale cavo di cellule staminali mesenchimali fodera.

&#x3053;&#x3053;&#x3067;&#x306F;&#x3001;&#x60A3;&#x8005;&#x26;gt; 65&#x6B73;&#x304B;&#x3089;&#x30D2;&#x30C8;&#x81CD;&#x5E2F;&#x30E9;&#x30A4;&#x30CB;&#x30F3;&#x30B0;&#x9593;&#x8449;&#x7CFB;&#x5E79;&#x7D30;&#x80DE;&#xFF08;clMSCs&#xFF09;&#x304A;&#x3088;&#x3073;&#x6210;&#x4EBA;&#x9AA8;&#x9AC4;&#x306E;MSC&#xFF08;bmMSCs&#xFF09;&#x3068;&#x306E;&#x9593;&#x306E;&#x514D;&#x75AB;&#x5B66;&#x7684;&#x306A;&#x4E00;&#x5BFE;&#x4E00;&#x306E;&#x6BD4;&#x8F03;&#x3092;&#x793A;&#x3059;&#x3002; clMSCs&#x306F;&#x6709;&#x610F;&#x306B;&#x4F4E;&#x3044;HLA&#x30AF;&#x30E9;&#x30B9;I&#x767A;&#x73FE;&#x3001;&#x514D;&#x75AB;&#x5BDB;&#x5BB9;TGF-&#x3B2;&#x3068;IL-10&#x306E;&#x9AD8;&#x3044;&#x751F;&#x7523;&#x3001;&#x5927;&#x5E45;&#x306B;&#x9AD8;&#x901F;&#x5897;&#x6B96;&#x304C;&#x8A8D;&#x3081;&#x3089;&#x308C;&#x3066;&#x3044;&#x307E;&#x3057;&#x305F;&#x3002; clMSCs&#x306E;&#x514D;&#x75AB;&#x8A8D;&#x8B58;&#x304C;&#x6709;&#x610F;&#x306B;&#x5F31;&#x304B;&#x3063;&#x305F;&#x306E;&#x306B;&#x5BFE;&#x3057;&#x3001;in vivo&#x3067;&#x306E;&#x514D;&#x75AB;&#x6D3B;&#x6027;&#x5316;&#x30EA;&#x30F3;&#x30D1;&#x7403;&#x540C;&#x7A2E;&#x304A;&#x3088;&#x3073;&#x7570;&#x7A2E;&#x306E;in vitro&#x3067;&#x306E;&#x6D3B;&#x6027;&#x5316;&#x306F;&#x3001;bmMSCs&#x6709;&#x610F;&#x306B;&#x5F37;&#x304B;&#x3063;&#x305F;&#x3002;&#x3057;&#x305F;&#x304C;&#x3063;&#x3066;&#x3001;bmMSCs&#x3092;&#x3088;&#x308A;&#x8FC5;&#x901F;&#x306B;&#x514D;&#x75AB;&#x30DE;&#x30A6;&#x30B9;&#x3067;&#x306F;&#x62D2;&#x5426;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002; IFN-&#x3B3;&#x3067;25 ng / ml&#x3067;&#x306F;&#x3001;TGF-&#x3B2;&#x3068;IL-10&#x653E;&#x51FA;&#x3092;&#x5897;&#x5927;&#x3055;&#x305B;&#x308B;&#x3068;&#x3001;&#x30A4;&#x30F3;&#x30C9;&#x30FC;&#x30EB;&#x30A2;&#x30DF;&#x30F3;&#x3092;&#x8A98;&#x5C0E;&#x3059;&#x308B;&#x3001;&#x7D30;&#x80DE;&#x5185;&#x306E;HLA-G&#x3068;&#x8868;&#x9762;HLA-E&#x306E;&#x767A;&#x73FE;&#x3092;&#x5897;&#x52A0;&#x3055;&#x305B;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x3063;&#x3066;HLA&#x30AF;&#x30E9;&#x30B9;I / HLA-DR&#x306E;&#x767A;&#x73FE;&#x3068;&#x5BDB;&#x5BB9;&#x539F;&#x6027;&#x306E;&#x30A2;&#x30C3;&#x30D7;&#x30EC;&#x30AE;&#x30E5;&#x30EC;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x306B;&#x3088;&#x308A;&#x3001;&#x4E21;&#x65B9;&#x306E;&#x514D;&#x75AB;&#x539F;&#x6027;&#x3092;&#x5897;&#x52A0;&#x3055;&#x305B;2,3  - &#x30B8;&#x30AA;&#x30AD;&#x30B7;&#x30B2;&#x30CA;&#x30FC;&#x30BC;&#xFF08;IDO&#xFF09;&#x306E;&#x767A;&#x73FE;&#x3002; IFN-&#x3B3;&#xFF08;&#x26;gt; 50 ng / ml&#xFF09;&#x306E;&#x9AD8;&#x3044;&#x6FC3;&#x5EA6;&#x304C;&#x3088;&#x308A;&#x4E00;&#x5C64;&#x5F37;&#x304F;HLA-DR&#x306E;&#x767A;&#x73FE;&#x3092;&#x30C0;&#x30A6;&#x30F3;&#x30EC;&#x30AE;&#x30E5;&#x30EC;&#x30FC;&#x30C8;&#x3057;&#x3001;&#x3055;&#x3089;&#x306B;IDO&#x306E;&#x751F;&#x7523;&#xFF08;500 ng / ml&#x3068;&#xFF09;&#x5897;&#x52A0;&#x3057;&#x3001;clMSCs&#x306E;&#x514D;&#x75AB;&#x8868;&#x73FE;&#x578B;&#x3092;&#x5897;&#x5F37;&#x3057;&#x305F;&#x3002; MSC&#x306E;&#x30CD;&#x30C3;&#x30C8;&#x6A5F;&#x80FD;&#x306E;&#x514D;&#x75AB;&#x6291;&#x5236;&#x52B9;&#x679C;&#x306F;&#x3001;&#x6DF7;&#x5408;&#x30EA;&#x30F3;&#x30D1;&#x7403;&#x57F9;&#x990A;&#x3067;&#x306F;&#x30C6;&#x30B9;&#x30C8;&#x3055;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002; clMSCs&#x3068;bmMSCs&#x4E21;&#x65B9;&#x304C;&#x5927;&#x5E45;&#x306B;in vitro&#x3067;&#x514D;&#x75AB;&#x6D3B;&#x6027;&#x5316;&#x306B;&#x6E1B;&#x5C11;&#x3057;&#x305F;&#x304C;&#x3001;clMSCs&#x306F;bmMSCs&#x3088;&#x308A;&#x3082;&#x5927;&#x5E45;&#x306B;&#x52B9;&#x679C;&#x7684;&#x3067;&#x3042;&#x3063;&#x305F;&#x3002;&#x4E21;&#x65B9;&#x306E;MSC&#x30E9;&#x30A4;&#x30F3;&#x306E;&#x62D2;&#x5426;&#x6A5F;&#x80FD;&#x306F;&#x30A8;&#x30B9;&#x30AB;&#x30EC;&#x30FC;&#x30C8;&#x3059;&#x308B;IFN-&#x3B3;&#x306E;&#x74B0;&#x5883;&#x3067;&#x62E1;&#x5F35;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x7D50;&#x8AD6;&#x3068;&#x3057;&#x3066;&#x3001;clMSCs&#x306F;&#x3001;&#x3088;&#x308A;&#x6709;&#x76CA;&#x306A;immunogeneic&#x30D7;&#x30ED;&#x30D5;&#x30A1;&#x30A4;&#x30EB;&#x3068;&#x9AD8;&#x9F62;bmMSCs&#x3088;&#x308A;&#x5F37;&#x304F;&#x5168;&#x4F53;&#x7684;&#x306A;&#x514D;&#x75AB;&#x6291;&#x5236;&#x306E;&#x53EF;&#x80FD;&#x6027;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;

&#x81CD;&#x5E2F;&#x30E9;&#x30A4;&#x30CB;&#x30F3;&#x30B0;&#x9593;&#x8449;&#x7CFB;&#x5E79;&#x7D30;&#x80DE;&#x306E;&#x514D;&#x75AB;&#x539F;&#x6027;&#x3068;&#x514D;&#x75AB;&#x8ABF;&#x7BC0;&#x7279;&#x6027;

&#xC6B0;&#xB9AC; &#xC5EC;&#xAE30; &#xD658;&#xC790;&#xC5D0; &#xAC8C; &#xC11C; &#xC778;&#xAC04;&#xC758; &#xD0EF; &#xC548; &#xAC10; &#xC911;&#xAC04; &#xC5FD; &#xC904;&#xAE30; &#xC138;&#xD3EC; (clMSCs)&#xC640; &#xC131;&#xC778; &#xACE8; &#xC218; MSCs (bmMSCs) &#xC0AC;&#xC774;&#xC758; &#xB0B4;&#xBD84;&#xBE44;&#xD559; &#xBA38;&#xB9AC; &#xBE44;&#xAD50; &#xC81C;&#xC2DC; &amp;gt; 65 &#xC138;. clMSCs &#xD588;&#xB2E4; &#xD604;&#xC800; &#xD558; &#xAC8C; &#xB0AE;&#xC740; HLA &#xD074;&#xB798;&#xC2A4; &#xB098; &#xC2DD;&#xC744;, tolerogenic TGF-&beta;&#xC758; &#xB192;&#xC740; &#xC0DD;&#xC0B0; &#xBC0F; IL-10&#xACFC; &#xD6E8;&#xC52C; &#xBE60;&#xB978; &#xD655;&#xC0B0;&#xC744; &#xBCF4;&#xC600;&#xB2E4;. Clmscs&#xC758; &#xBA74;&#xC5ED; &#xC778;&#xC2DD; &#xD06C;&#xAC8C; &#xC57D;&#xD55C; &#xBC18;&#xBA74; allogeneic &#xC138;&#xD3EC;&#xC758; &#xCCB4; &#xC678; &#xD65C;&#xC131;&#xD654;&#xC640; &#xBA74;&#xC5ED; &#xD65C;&#xC131;&#xD654; xenogeneic vivo&#xC5D0;&#xC11C; &#xD06C;&#xAC8C; &#xAC15;&#xD574; bmMSCs, &#xD568;&#xAED8; &#xD588;&#xB2E4;. &#xB530;&#xB77C;&#xC11C;, bmMSCs immunocompetent &#xC950;&#xC5D0;&#xC11C; &#xBCF4;&#xB2E4; &#xC2E0;&#xC18D; &#xD558; &#xAC8C; &#xAC70;&#xBD80; &#xD588;&#xB2E4;. 25 Ng/ml&#xC5D0;&#xC11C; IFN-&gamma; &#xC99D;&#xAC00; &#xBAA8;&#xB450; HLA&#xC758; upregulation &#xC5EC; immunogenicity &#xD074;&#xB798;&#xC2A4; I / HLA-DR &#xD45C;&#xD604;&#xACFC; tolerogenicity &#xC138;&#xD3EC;&#xB0B4; HLA-G &#xBC0F; &#xD45C;&#xBA74; HLA-E &#xC2DD; &#xB298;&#xB824; TGF-&beta;&#xC640; IL-10 &#xB9B4;&#xB9AC;&#xC2A4;&#xB97C; &#xBCF4;&#xAC15; &#xD558; &#xACE0; indoleamine 2, 3-dioxygenase (IDO) &#xC2DD; &#xC720;&#xB3C4;. IFN-&gamma;&#xC758; &#xB192;&#xC740; &#xB18D;&#xB3C4; (&amp;gt; 50 ng/ml) &#xB354; clMSCs, &#xB354; &#xAC15;&#xB825; &#xD558; &#xAC8C; downregulating HLA-DR &#xC2DD; &#xBC0F; &#xCD94;&#xAC00; (500 ng/ml)&#xC5D0;&#xC11C;&#xB3C4; &#xC0DD;&#xC0B0; &#xC99D;&#xAC00;&#xC758; &#xBA74;&#xC5ED; &#xD45C;&#xD604; &#xD615;&#xC744; &#xAC15;&#xD654;. &#xD63C;&#xD569;&#xB41C; &#xB9BC;&#xD504; &#xAD6C; &#xBB38;&#xD654; Mscs&#xC758; &#xC21C; &#xAE30;&#xB2A5;&#xC801; &#xBA74;&#xC5ED; &#xD6A8;&#xB2A5; &#xD14C;&#xC2A4;&#xD2B8; &#xD588;&#xC2B5;&#xB2C8;&#xB2E4;. Clmscs&#xC640; bmMSCs &#xB458; &#xB2E4; &#xD06C;&#xAC8C; &#xC0DD;&#xCCB4; &#xC678;&#xC5D0;&#xC11C; &#xBA74;&#xC5ED; &#xD65C;&#xC131;&#xD654;&#xB97C; &#xAC10;&#xC18C;, clMSCs bmMSCs &#xBCF4;&#xB2E4; &#xD6E8;&#xC52C; &#xB354; &#xD6A8;&#xACFC;&#xC801; &#xC774;&#xC5C8;&#xB2E4;. MSC &#xB77C;&#xC778;&#xC758; &#xAC70;&#xBD80;&#xAD8C; &#xD568;&#xC218; &#xACE0;&#xC870; IFN-&gamma; &#xD658;&#xACBD;&#xC5D0;&#xC11C; &#xD5A5;&#xC0C1; &#xB418;&#xC5C8;&#xC2B5;&#xB2C8;&#xB2E4;. &#xB05D;&#xC73C;&#xB85C;, clMSCs &#xB354; &#xB3C4;&#xC6C0;&#xC774; immunogeneic &#xD504;&#xB85C;&#xD544; &#xBC0F; &#xC138; bmMSCs &#xBCF4;&#xB2E4; &#xB354; &#xAC15;&#xD55C; &#xC804;&#xBC18;&#xC801;&#xC778; &#xBA74;&#xC5ED; &#xC7A0;&#xC7AC;&#xB825; &#xBCF4;&#xC5EC; &#xC90D;&#xB2C8;&#xB2E4;.

&#xBC30;&#xAF3D;&#xC758; immunomodulatory &#xC18D;&#xC131;&#xACFC; immunogenicity &#xB77C;&#xC774;&#xB2DD; &#xC911;&#xAC04; &#xC5FD; &#xC904;&#xAE30; &#xC138;&#xD3EC;&#xB97C; &#xCF54;&#xB4DC;.

A continuaci&#xF3;n presentamos un efecto inmunol&#xF3;gico de la cabeza a cabeza la comparaci&#xF3;n entre humanos umbilical c&#xE9;lulas de revestimiento de la m&#xE9;dula madre mesenquimales (clMSCs) y adultos de m&#xE9;dula &#xF3;sea MSC (bmMSCs) de los pacientes mayores de 65 a&#xF1;os de edad. clMSCs ten&#xED;an significativamente menor HLA clase I de expresi&#xF3;n, una mayor producci&#xF3;n de tolerog&#xE9;nico TGF-&#x3B2; y la IL-10, y mostr&#xF3; proliferaci&#xF3;n significativamente m&#xE1;s r&#xE1;pido. In vitro, la activaci&#xF3;n de los linfocitos alog&#xE9;nicos y xenog&#xE9;nicos en la activaci&#xF3;n inmune in vivo fue significativamente m&#xE1;s fuerte con bmMSCs, mientras que el reconocimiento inmune de clMSCs fue significativamente m&#xE1;s d&#xE9;bil. As&#xED;, se bmMSCs m&#xE1;s r&#xE1;pidamente rechazado en ratones inmunocompetentes. IFN-&#x3B3; a 25 ng / ml aument&#xF3; tanto inmunogenicidad por la regulaci&#xF3;n positiva de HLA de clase I / expresi&#xF3;n de HLA-DR y tolerogenicity mediante el aumento intracelular de HLA-G y expresi&#xF3;n en la superficie HLA-E, aumentando la liberaci&#xF3;n de TGF-&#x3B2; y la IL-10, e induciendo indolamina 2,3-dioxigenasa (IDO) expresi&#xF3;n. Mayores concentraciones de IFN-&#x3B3; (&#x26;gt; 50 ng / ml) mejora a&#xFA;n m&#xE1;s el fenotipo inmunosupresor de clMSCs, m&#xE1;s fuertemente downregulating expresi&#xF3;n de HLA-DR y aumentando a&#xFA;n m&#xE1;s la producci&#xF3;n de IDO (a 500 ng / ml). La red de eficacia funcional inmunosupresor de las MSC ha sido probado en cultivos mixtos de linfocitos. Aunque ambos clMSCs y bmMSCs redujo significativamente la activaci&#xF3;n in vitro inmune, clMSCs fueron significativamente m&#xE1;s eficaz que bmMSCs. El derecho de veto de las dos l&#xED;neas de MSC se mejor&#xF3; en la escalada de IFN-gamma entornos. En conclusi&#xF3;n, clMSCs muestran un perfil inmunog&#xE9;nicas, m&#xE1;s beneficioso y m&#xE1;s fuerte que el potencial global inmunosupresora bmMSCs edad.

Inmunogenicidad y el inmunomodulador de las c&#xE9;lulas de revestimiento del cord&#xF3;n umbilical madre mesenquimales

The transcription factor Islet-1 is a marker of cardiovascular progenitors during embryogenesis. The isolation of Islet-1-positive (Islet-1(+)) cells from early postnatal hearts suggested that Islet-1 also marks cardiac progenitors in adult life. Objective: We investigated the distribution and identity of Islet-1(+) cells in adult murine heart and evaluated whether their number or distribution change with age or after myocardial infarction.

Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart.

Selective inhibition of lymphocyte activation through abrogation of signal 3-cytokine transduction emerges as a new strategy for immunosuppression. This is the first report on the novel Janus kinase (JAK)1/3 inhibitors R507 and R545 for prevention of acute allograft rejection.

Significant reduction of acute cardiac allograft rejection by selective janus kinase-1/3 inhibition using R507 and R545.

The calcium-activated potassium channel KCa3.1 is critically involved in T-cell activation as well as in the proliferation of smooth muscle cells and fibroblasts. We sought to investigate whether KCa3.1 contributes to the pathogenesis of obliterative airway disease (OAD) and whether knockout or pharmacologic blockade would prevent the development of OAD.

The potassium channel KCa3.1 as new therapeutic target for the prevention of obliterative airway disease.

Gaining cardiac surgical competence is a complex, multifactorial process that may take years of experience and on-the-job training. It is critical to provide suitable educational opportunities to gain the necessary knowledge, judgment and skills. In response to the multitude of factors (e.g. European Working Time Directive) currently influencing cardiac surgical training, there have been concerted efforts to reform training practices. Simulation plays an increasingly important role in the educational process and serves to fill the most important gap in the current training model, i.e. operative exposure. Therefore, a contest has been written out for cardiac surgical trainees to construct their own coronary anastomosis simulator using everyday materials.

How to build your own coronary anastomosis simulator from scratch.

Mesenchymal stromal cells (MSCs) have been isolated from many tissues, including gestational tissue. To date, a study comparing the properties and suitability of these cells in cell-based therapies is lacking. In this study, we compared the phenotype, proliferation rate, migration, immunogenicity, and immunomodulatory capabilities of human MSCs derived from umbilical cord lining (CL-MSCs), umbilical cord blood (CB-MSCs), placenta (P-MSCs), and Wharton's jelly (WJ-MSCs). Differences were noted in differentiation, proliferation, and migration, with CL-MSCs showing the highest proliferation and migration rates resulting in prolonged survival in immunodeficient mice. Moreover, CL-MSCs showed a prolongation in survival in xenogeneic BALB/c mice, which was attributed to their ability to dampen TH1 and TH2 responses. Weaker human cellular immune responses were detected against CL-MSCs and P-MSCs, which were correlated with their lower HLA I expression. Furthermore, HLA II was upregulated less substantially by CL-MSCs and CB-MSCs after IFN-γ stimulation. MSC types did not differ in indolamine 2,3-dioxygenase (IDO) expression after IFN-γ stimulation. Despite their lower IDO, HLA-G, and TGF-β1 expression, only CL-MSCs were able to reduce the release of IFN-γ by lymphocytes in a mixed lymphocyte reaction. In summary, CL-MSCs showed the best characteristics for cell-based strategies, as they are hypo-immunogenic and show high proliferation and migration rates. In addition, these studies show for the first time that although immunomodulatory molecules HLA-G, HLA-E, and TGF-β play an important role in MSC immune evasion, basal and induced HLA expression seems to be decisive in determining the immunogenicity of MSCs.

Immunological properties of extraembryonic human mesenchymal stromal cells derived from gestational tissue.

Despite the introduction of antiproliferative drug-eluting stents, coronary heart disease remains the leading cause of death in the United States. In-stent restenosis and bypass graft failure are characterized by excessive smooth muscle cell (SMC) proliferation and concomitant myointima formation with luminal obliteration. Here we show that during the development of myointimal hyperplasia in human arteries, SMCs show hyperpolarization of their mitochondrial membrane potential (ΔΨm) and acquire a temporary state with a high proliferative rate and resistance to apoptosis. Pyruvate dehydrogenase kinase isoform 2 (PDK2) was identified as a key regulatory protein, and its activation proved necessary for relevant myointima formation. Pharmacologic PDK2 blockade with dichloroacetate or lentiviral PDK2 knockdown prevented ΔΨm hyperpolarization, facilitated apoptosis and reduced myointima formation in injured human mammary and coronary arteries, rat aortas, rabbit iliac arteries and swine (pig) coronary arteries. In contrast to several commonly used antiproliferative drugs, dichloroacetate did not prevent vessel re-endothelialization. Targeting myointimal ΔΨm and alleviating apoptosis resistance is a novel strategy for the prevention of proliferative vascular diseases.

ArticleTotal : 2	Year
Publication title Cited by 7	2010
Publication title Cited by 8	2014

Article	Year
Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells. Cell transplantation\| PubMed ID: 21054940	2011
Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart. Circulation research\| PubMed ID: 22427341	2012
Significant reduction of acute cardiac allograft rejection by selective janus kinase-1/3 inhibition using R507 and R545. Transplantation\| PubMed ID: 22971540	2012
The potassium channel KCa3.1 as new therapeutic target for the prevention of obliterative airway disease. Transplantation\| PubMed ID: 23325003	2013
How to build your own coronary anastomosis simulator from scratch. Interactive cardiovascular and thoracic surgery\| PubMed ID: 23456683	2013
Immunological properties of extraembryonic human mesenchymal stromal cells derived from gestational tissue. Stem cells and development\| PubMed ID: 23711207	2013
Dichloroacetate prevents restenosis in preclinical animal models of vessel injury. Nature\| PubMed ID: 24747400	2014

Mandy Stubbendorff

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