isolation-blood-vessel-derived-multipotent-precursors-from-human

Isolation of Blood-vessel-derived Multipotent Precursors from Human Skeletal Muscle

Since the discovery of mesenchymal stem/stromal cells (MSCs), the native identity and localization&#160;of MSCs have been obscured by their retrospective ...

isolation-perivascular-multipotent-precursor-cell-populations-from

Isolation of Perivascular Multipotent Precursor Cell Populations from Human Cardiac Tissue

Multipotent mesenchymal stem/stromal cells (MSC) were conventionally isolated, through their plastic adherence, from primary tissue digests whilst their ...

University of Pittsburgh

Massachusetts Institute of Technology

&#x5177;&#x6709;&#x6700;&#x9AD8;&#x6548;&#x529B;&#x7684;&#x7EC6;&#x80DE;&#x7684;&#x9274;&#x5B9A;&#x53EF;&#x80FD;&#x662F;&#x57FA;&#x4E8E;&#x7EC6;&#x80DE;&#x7597;&#x6CD5;&#x7684;&#x4E34;&#x5E8A;&#x6210;&#x529F;&#x7684;&#x5173;&#x952E;&#x3002;&#x6211;&#x4EEC;&#x8C03;&#x67E5;&#x4E86;&#x662F;&#x5426;&#x80FD;&#x5230;&#x7EC4;&#x57F9;&#x74F6;&#x540E;&#x7EC4;&#x7EC7;&#x89E3;&#x79BB;&#x4ECE;&#x6210;&#x4EBA;&#x4EBA;&#x4F53;&#x9AA8;&#x9ABC;&#x808C;&#x8089;&#x53CA;&#x5176;&#x80F6;&#x5408;&#x6027;&#x80FD;&#x7684;&#x57FA;&#x7840;&#x4E0A;&#x4E30;&#x5BCC;&#x5177;&#x6709;&#x589E;&#x5F3A;&#x5FC3;&#x808C;&#x7EC6;&#x80DE;&#x7597;&#x6CD5;&#x7597;&#x6548;&#x7684;&#x5355;&#x5143;&#x683C;&#x3002;&#x6162;&#x6162;&#x5730;&#x9075;&#x5B88;&#x7684;&#x5355;&#x5143;&#x683C;&#x663E;&#x793A;&#x808C;&#x7EAF;&#x5EA6;&#x66F4;&#x9AD8;&#x548C;&#x66F4;&#x5BB9;&#x6613;&#x5206;&#x5316;&#x4E3A;&#x808C;&#x7BA1;&#x4F53;&#x5916;&#x6BD4;&#x8FC5;&#x901F;&#x79C9;&#x627F;&#x7EC6;&#x80DE; (Rac)&#x3002;&#x6162;&#x6162;&#x5730;&#x7C98;&#x9644;&#x7EC6;&#x80DE; (SAC) &#x4EBA;&#x53E3;&#x8FD8;&#x5E78;&#x5B58;&#x4E0B;&#x6765;&#x6BD4;&#x6A21;&#x62DF;&#x7684;&#x6C27;&#x5316;&#x548C;&#x708E;&#x75C7;&#x7684;&#x5E94;&#x529B;&#x6761;&#x4EF6;&#x7684;&#x52A8;&#x529B;&#x5B66;&#x4F53;&#x5916;&#x68C0;&#x6D4B;&#x7684; RAC &#x4EBA;&#x53E3;&#x66F4;&#x597D;&#x3002;&#x5728;&#x8BA1;&#x7B97;&#x65F6;&#x6CBB;&#x7597;&#x5FC3;&#x808C;&#x6897;&#x6B7B; (MI)&#xFF0C;intramyocardial &#x56CA;&#x6CE8;&#x5C04;&#x66F4;&#x6709;&#x6548;&#x6539;&#x5584;&#x5DE6;&#x5FC3;&#x5BA4; &#xFF08;LV&#xFF09; &#x91CD;&#x6784;&#x53CA;&#x6536;&#x7F29;&#x529F;&#x80FD;&#x7684;&#x8D85;&#x58F0;&#x5FC3;&#x52A8;&#x56FE;&#x7D22;&#x5F15;&#x6BD4; Rac &#x7684;&#x79FB;&#x690D;&#x3002;&#x514D;&#x75AB;&#x7EC4;&#x7EC7;&#x5316;&#x5B66;&#x5206;&#x6790;&#x7ED3;&#x679C;&#x8868;&#x660E;&#x5FC3;&#x56CA;&#x6CE8;&#x5C04;&#x5728;&#x5FC3;&#x808C;&#x7EA4;&#x7EF4;&#x5316;&#x548C;&#x6897;&#x6B7B;&#x8840;&#x7BA1;&#x3001; &#x6350;&#x52A9;&#x7EC6;&#x80DE;&#x589E;&#x6B96;&#xFF0C;&#x548C;&#x5185;&#x6E90;&#x6027;&#x5FC3;&#x808C;&#x7EC6;&#x80DE;&#x5B58;&#x6D3B;&#x548C;&#x589E;&#x6B96;&#x4E0E; RAC &#x6CBB;&#x7597;&#x5FC3;&#x589E;&#x52A0;&#x663E;&#x793A;&#x51CF;&#x5C11;&#x4E86;&#x3002;&#x603B;&#x4E4B;&#xFF0C;&#x8FD9;&#x4E9B;&#x7ED3;&#x679C;&#x8868;&#x660E;&#x6210;&#x4EBA;&#x4EBA;&#x4F53;&#x9AA8;&#x9ABC;&#x808C;&#x8089;&#x7EC6;&#x80DE;&#x5BF9;&#x5176;&#x7597;&#x6548;&#x4F18;&#x4E8E; Rac &#x56CA;&#x540E;&#x5FC3;&#x810F;&#x690D;&#x5165;&#xFF0C;&#x52A0;&#x5F3A;&#x5FC3;&#x810F;&#x529F;&#x80FD;&#x672C;&#x8D28;&#x4E0A;&#x662F;&#x5F02;&#x7C7B;&#x3002;

&#x4EBA;&#x9AA8;&#x9ABC;&#x808C;&#x7EC6;&#x80DE;&#x4E0E;&#x6162;&#x7C98;&#x9644;&#x7387;&#x540E;&#x9694;&#x79BB;&#x548C;&#x589E;&#x5F3A;&#x7684;&#x6297;&#x9006;&#x6027;&#x6539;&#x5584;&#x7F3A;&#x8840;&#x5FC3;&#x810F;&#x7684;&#x529F;&#x80FD;&#x3002;

Identification of cells that are endowed with maximum potency could be critical for the clinical success of cell-based therapies. We investigated whether cells with an enhanced efficacy for cardiac cell therapy could be enriched from adult human skeletal muscle on the basis of their adhesion properties to tissue culture flasks following tissue dissociation. Cells that adhered slowly displayed greater myogenic purity and more readily differentiated into myotubes in vitro than rapidly adhering cells (RACs). The slowly adhering cell (SAC) population also survived better than the RAC population in kinetic in vitro assays that simulate conditions of oxidative and inflammatory stress. When evaluated for the treatment of a myocardial infarction (MI), intramyocardial injection of the SACs more effectively improved echocardiographic indexes of left ventricular (LV) remodeling and contractility than the transplantation of the RACs. Immunohistological analysis revealed that hearts injected with SACs displayed a reduction in myocardial fibrosis and an increase in infarct vascularization, donor cell proliferation, and endogenous cardiomyocyte survival and proliferation in comparison with the RAC-treated hearts. In conclusion, these results suggest that adult human skeletal muscle-derived cells are inherently heterogeneous with regard to their efficacy for enhancing cardiac function after cardiac implantation, with SACs outperforming RACs.

Human skeletal muscle cells with a slow adhesion rate after isolation and an enhanced stress resistance improve function of ischemic hearts.

Identification des cellules qui sont dot&#xE9;s d&#x26;#39;une puissance maximale pourrait &#xEA;tre d&#xE9;terminante pour le succ&#xE8;s clinique de th&#xE9;rapies cellulaires. Nous avons &#xE9;tudi&#xE9; si les cellules avec une efficacit&#xE9; accrue pour la th&#xE9;rapie cellulaire cardiaque pourrait &#xEA;tre enrichie &#xE0; partir des adultes du muscle squelettique humain sur la base de leurs propri&#xE9;t&#xE9;s d&#x26;#39;adh&#xE9;rence &#xE0; des flacons de culture tissulaire &#xE0; la suite de dissociation des tissus. Les cellules qui ont adh&#xE9;r&#xE9; lentement affich&#xE9;s une plus grande puret&#xE9; myog&#xE9;nique et plus facilement diff&#xE9;renci&#xE9;es en myotubes in vitro que les cellules adh&#xE8;rent rapidement (CCR). La cellule lentement adh&#xE9;rant (SAC) de la population a &#xE9;galement surv&#xE9;cu mieux que la population RAC en cin&#xE9;tique des essais in vitro qui simulent des conditions de stress oxydatif et inflammatoire. Lorsque &#xE9;valu&#xE9; pour le traitement d&#x26;#39;un infarctus du myocarde (IM), injection intra-myocardique des ZSC plus efficacement am&#xE9;lior&#xE9; les indices &#xE9;chocardiographiques du ventricule gauche (VG) et de la contractilit&#xE9; de la transplantation des CCR. L&#x26;#39;analyse immunohistologique a r&#xE9;v&#xE9;l&#xE9; que les c&#x153;urs inject&#xE9;s avec ZSC affich&#xE9; une r&#xE9;duction de la fibrose myocardique et une augmentation de la vascularisation du myocarde, la prolif&#xE9;ration cellulaire des bailleurs de fonds, et la survie des cardiomyocytes endog&#xE8;ne et de la prolif&#xE9;ration en comparaison avec les coeurs RAC-trait&#xE9;s. En conclusion, ces r&#xE9;sultats sugg&#xE8;rent que les adultes de l&#x26;#39;homme le muscle squelettique des cellules d&#xE9;riv&#xE9;es sont fondamentalement h&#xE9;t&#xE9;rog&#xE8;ne en ce qui concerne leur efficacit&#xE9; pour am&#xE9;liorer la fonction cardiaque apr&#xE8;s l&#x26;#39;implantation cardiaque, avec ZSC surperformant CCR.

Cellules musculaires squelettiques humaines avec un taux d&#x26;#39;adh&#xE9;rence lent apr&#xE8;s isolation et une r&#xE9;sistance au stress am&#xE9;lior&#xE9;e am&#xE9;liorer la fonction de c&#x153;urs isch&#xE9;miques

Identifizierung der Zellen, die &uuml;ber eine maximale Potenz verf&uuml;gen k&ouml;nnte f&uuml;r den klinischen Erfolg zellbasierte Therapien entscheidend. Wir untersucht, ob die Zellen mit einer verbesserten Wirksamkeit Herzzelle Therapie von Erwachsenen menschlichen Skelettmuskulatur aufgrund ihrer Adh&auml;sion Eigenschaften Gewebekultur Kolben nach Gewebe Dissoziation bereichert werden k&ouml;nnte. Zellen, die langsam verklebt angezeigt gr&ouml;&szlig;er Myogener Reinheit und mehr leicht unterschieden in Myotubes in-vitro-als schnell festhalten (RAC) Zellen. Die langsam haftende Zellpopulation (SAC) &uuml;berlebte auch besser als die RAC-Bev&ouml;lkerung in kinetische in-vitro-Tests, die Bedingungen des oxidativen und entz&uuml;ndlichen Stress zu simulieren. Wenn f&uuml;r die Behandlung von einem Myokardinfarkt (MI) ausgewertet, verbessert intramyocardial Injektion von der SACs intertrabekul&auml;re Indizes der linke Ventrikel (LV) Umbau und Kontraktilit&auml;t effektiver als die Transplantation der regionalen Beir&auml;te. Immunohistological-Analyse ergab, dass Herz injiziert mit SACs eine Reduktion im myokardialen Fibrose und eine Erh&ouml;hung der Infarkt Vaskularisierung, Spender-Zellproliferation und endogene Cardiomyocyte &uuml;berleben und Verbreitung im Vergleich zu den RAC-behandelten Herzen angezeigt. Diesen Ergebnissen zufolge abschlie&szlig;end Erwachsene menschliche skelettartiger Muskel gewonnenen Zellen im Hinblick auf ihre Wirksamkeit f&uuml;r die Verbesserung der Herzfunktion nach kardialen Implantation mit SACs &uuml;bertrifft Beir&auml;te von Natur aus heterogen sind.

Menschliche Skelettmuskel-Zellen mit einer langsamen Adh&auml;sion nach Isolierung und eine verbesserte Stressresistenz Funktion der isch&auml;mischen Herzen verbessern.

Identificazione delle cellule che sono dotati di potenza massima potrebbe essere fondamentale per il successo clinico di terapie cell-based. Abbiamo studiato se cellule con maggiore efficacia per la terapia cellulare cardiaca potrebbero essere arricchite da muscolo scheletrico umano adulto in base alle loro propriet&agrave; di adesione a boccette di coltura del tessuto seguendo la dissociazione dei tessuti. Le cellule che aderiscono lentamente visualizzato maggiore purezza miogena e pi&ugrave; facilmente differenziato in myotubes in vitro che aderiscono rapidamente le cellule (RAC). La popolazione cellulare (SAC) lentamente aderente sopravvisse anche meglio rispetto alla popolazione di RAC in cinetiche saggi in vitro che simulano le condizioni di stress ossidativo e infiammatorio. Quando valutato per il trattamento di un infarto del miocardio (MI), iniezione intramyocardial del SACs migliorato pi&ugrave; efficacemente gli indici ecocardiografici di sinistra (LV) rimodellamento ventricolare e la contrattilit&agrave; rispetto al trapianto dei CCR. L&#39;analisi immunoistochimica ha rivelato che cuori iniettati con SACs visualizzata una riduzione nella fibrosi miocardica e un aumento della vascolarizzazione infarct, proliferazione di cellule del donatore ed endogeno cardiomyocyte sopravvivenza e proliferazione nel confronto con i cuori RAC-trattati. In conclusione, questi risultati suggeriscono che umane scheletriche muscolo-derivate cellule adulte sono intrinsecamente eterogenee per quanto riguarda la loro efficacia per migliorare la funzione cardiaca dopo impianto cardiaco, con SACs superando RAC.

Cellule del muscolo scheletrico umano con un tasso di adesione lento dopo l&#39;isolamento e una resistenza maggiore sforzo migliorare la funzione del cuore ischemico.

&#x6700;&#x5927;&#x52B9;&#x529B;&#x306B;&#x6075;&#x307E;&#x308C;&#x3066;&#x3044;&#x308B;&#x7D30;&#x80DE;&#x306E;&#x540C;&#x5B9A;&#x306F;&#x3001;&#x7D30;&#x80DE;&#x30D9;&#x30FC;&#x30B9;&#x306E;&#x6CBB;&#x7642;&#x6CD5;&#x306E;&#x81E8;&#x5E8A;&#x7684;&#x6210;&#x529F;&#x306B;&#x3068;&#x3063;&#x3066;&#x91CD;&#x8981;&#x3067;&#x3042;&#x308B;&#x53EF;&#x80FD;&#x6027;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005;&#x306F;&#x5FC3;&#x7B4B;&#x7D30;&#x80DE;&#x7642;&#x6CD5;&#x306E;&#x305F;&#x3081;&#x306E;&#x5F37;&#x5316;&#x3055;&#x308C;&#x305F;&#x52B9;&#x679C;&#x3092;&#x6301;&#x3064;&#x7D30;&#x80DE;&#x306F;&#x3001;&#x7D44;&#x7E54;&#x89E3;&#x96E2;&#x5F8C;&#x306B;&#x7D44;&#x7E54;&#x57F9;&#x990A;&#x30D5;&#x30E9;&#x30B9;&#x30B3;&#x3078;&#x306E;&#x63A5;&#x7740;&#x7279;&#x6027;&#x306B;&#x57FA;&#x3065;&#x3044;&#x3066;&#x6210;&#x4EBA;&#x30D2;&#x30C8;&#x9AA8;&#x683C;&#x7B4B;&#x304B;&#x3089;&#x6FC3;&#x7E2E;&#x3059;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x305F;&#x304B;&#x3069;&#x3046;&#x304B;&#x3092;&#x8ABF;&#x3079;&#x305F;&#x3002;&#x4ED8;&#x7740;&#x3057;&#x3066;&#x6025;&#x901F;&#x306B;&#x4ED8;&#x7740;&#x3057;&#x305F;&#x7D30;&#x80DE;&#xFF08;RAC&#xFF09;&#x306E;&#x3088;&#x308A;&#x3086;&#x3063;&#x304F;&#x308A;&#x3068;&#x5927;&#x304D;&#x306A;&#x7B4B;&#x7D14;&#x5EA6;&#x304C;&#x8868;&#x793A;&#x3055;&#x308C;&#x3001;&#x3088;&#x308A;&#x5BB9;&#x6613;&#x306B;in vitro&#x3067;&#x7B4B;&#x7BA1;&#x306B;&#x5206;&#x5316;&#x3059;&#x308B;&#x7D30;&#x80DE;&#x3002;&#x5F90;&#x3005;&#x306B;&#x4ED8;&#x7740;&#x3057;&#x305F;&#x7D30;&#x80DE;&#xFF08;SAC&#xFF09;&#x306E;&#x4EBA;&#x53E3;&#x306F;&#x3001;&#x9178;&#x5316;&#x30B9;&#x30C8;&#x30EC;&#x30B9;&#x3084;&#x708E;&#x75C7;&#x6027;&#x306E;&#x6761;&#x4EF6;&#x3092;&#x30B7;&#x30DF;&#x30E5;&#x30EC;&#x30FC;&#x30C8;&#x3059;&#x308B;in vitro&#x30A2;&#x30C3;&#x30BB;&#x30A4;&#x904B;&#x52D5;&#x306B;&#x304A;&#x3051;&#x308B;RAC&#x306E;&#x4EBA;&#x53E3;&#x3088;&#x308A;&#x3082;&#x512A;&#x308C;&#x3066;&#x751F;&#x304D;&#x6B8B;&#x3063;&#x305F;&#x3002;&#x5FC3;&#x7B4B;&#x6897;&#x585E;&#xFF08;MI&#xFF09;&#x306E;&#x6CBB;&#x7642;&#x306E;&#x305F;&#x3081;&#x306B;&#x8A55;&#x4FA1;&#x3055;&#x308C;&#x308B;&#x3068;&#x304D;&#x306B;&#x3001;&#x6C17;&#x56A2;&#x306E;&#x5FC3;&#x7B4B;&#x5185;&#x6CE8;&#x5C04;&#x304C;&#x3088;&#x308A;&#x52B9;&#x679C;&#x7684;&#x306B;RAC&#x306E;&#x79FB;&#x690D;&#x3088;&#x308A;&#x3082;&#x3001;&#x5DE6;&#x5FC3;&#x5BA4;&#xFF08;LV&#xFF09;&#x30EA;&#x30E2;&#x30C7;&#x30EA;&#x30F3;&#x30B0;&#x3068;&#x53CE;&#x7E2E;&#x6027;&#x5FC3;&#x30A8;&#x30B3;&#x30FC;&#x306E;&#x30A4;&#x30F3;&#x30C7;&#x30C3;&#x30AF;&#x30B9;&#x3092;&#x6539;&#x5584;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x514D;&#x75AB;&#x7D44;&#x7E54;&#x5B66;&#x7684;&#x89E3;&#x6790;&#x3067;&#x306F;&#x3001;&#x5FC3;&#x304C;&#x5FC3;&#x7B4B;&#x7DDA;&#x7DAD;&#x75C7;&#x306E;&#x6E1B;&#x5C11;&#x3068;&#x6897;&#x585E;&#x8840;&#x7BA1;&#x65B0;&#x751F;&#x306E;&#x5897;&#x52A0;&#x306F;&#x3001;&#x30C9;&#x30CA;&#x30FC;&#x7D30;&#x80DE;&#x306E;&#x5897;&#x6B96;&#x3001;&#x304A;&#x3088;&#x3073;RAC&#x51E6;&#x7406;&#x3055;&#x308C;&#x305F;&#x5FC3;&#x3068;&#x6BD4;&#x8F03;&#x3057;&#x3066;&#x5185;&#x56E0;&#x6027;&#x306E;&#x5FC3;&#x7B4B;&#x7D30;&#x80DE;&#x306E;&#x751F;&#x5B58;&#x3068;&#x5897;&#x6B96;&#x3092;&#x8868;&#x793A;&#x56A2;&#x306B;&#x6CE8;&#x5165;&#x3055;&#x308C;&#x305F;&#x3053;&#x3068;&#x3092;&#x660E;&#x3089;&#x304B;&#x306B;&#x3057;&#x305F;&#x3002;&#x7D50;&#x8AD6;&#x3068;&#x3057;&#x3066;&#x3001;&#x3053;&#x308C;&#x3089;&#x306E;&#x7D50;&#x679C;&#x306F;&#x3001;&#x6210;&#x4EBA;&#x306E;&#x30D2;&#x30C8;&#x9AA8;&#x683C;&#x7B4B;&#x7531;&#x6765;&#x7D30;&#x80DE;&#x306F;&#x56A2;&#x306F;RAC&#x3092;&#x4E0A;&#x56DE;&#x308B;&#x3068;&#x3001;&#x5FC3;&#x81D3;&#x79FB;&#x690D;&#x5F8C;&#x5FC3;&#x6A5F;&#x80FD;&#x3092;&#x5411;&#x4E0A;&#x3055;&#x305B;&#x308B;&#x305F;&#x3081;&#x306E;&#x305D;&#x306E;&#x6709;&#x52B9;&#x6027;&#x306B;&#x95A2;&#x3057;&#x3066;&#x672C;&#x8CEA;&#x7684;&#x306B;&#x4E0D;&#x5747;&#x4E00;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;

&#x5206;&#x96E2;&#x5F8C;&#x306E;&#x30B9;&#x30ED;&#x30FC;&#x4ED8;&#x7740;&#x7387;&#x3068;&#x5F37;&#x5316;&#x3055;&#x308C;&#x305F;&#x30B9;&#x30C8;&#x30EC;&#x30B9;&#x62B5;&#x6297;&#x6027;&#x3092;&#x6709;&#x3059;&#x308B;&#x30D2;&#x30C8;&#x9AA8;&#x683C;&#x7B4B;&#x7D30;&#x80DE;&#x306F;&#x3001;&#x865A;&#x8840;&#x6027;&#x5FC3;&#x306E;&#x6A5F;&#x80FD;&#x3092;&#x6539;&#x5584;&#x3059;&#x308B;

&#xCD5C;&#xB300; &#xD798;&#xC744; &#xBD80;&#xC5EC; &#xD558;&#xB294; &#xC140;&#xC758; &#xC140; &#xAE30;&#xBC18; &#xC694;&#xBC95;&#xC758; &#xC784;&#xC0C1; &#xC131;&#xACF5;&#xC5D0; &#xB300; &#xD55C; &#xC911;&#xC694; &#xD55C; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xC2EC;&#xC7A5; &#xC138;&#xD3EC; &#xCE58;&#xB8CC;&#xC5D0; &#xB300; &#xD55C; &#xD5A5;&#xC0C1; &#xB41C; &#xD6A8;&#xB2A5;&#xC73C;&#xB85C; &#xC138;&#xD3EC; &#xC870;&#xC9C1; &#xBD84;&#xB9AC;&#xC5D0; &#xB530;&#xB77C; &#xC870;&#xC9C1; &#xBC30;&#xC591; &#xD50C;&#xB77C;&#xC2A4; &#xD06C;&#xB97C; &#xC811;&#xCC29; &#xC18D;&#xC131;&#xC5D0; &#xAE30;&#xCD08; &#xD558; &#xC5EC; &#xC131;&#xC778; &#xC778;&#xAC04;&#xC758; &#xACE8;&#xACA9; &#xADFC;&#xC5D0;&#xC11C; &#xB18D;&#xCD95; &#xC218; &#xC5EC;&#xBD80;&#xB97C; &#xC870;&#xC0AC; &#xD588;&#xB2E4;. &#xCC9C;&#xCC9C;&#xD788; &#xC900;&#xC218; &#xC140; &#xD45C;&#xC2DC; &#xD070; myogenic &#xC21C;&#xB3C4; myotubes &#xC2DC;&#xB0B4; (Rac) &#xC138;&#xD3EC;&#xAC00; &#xAE09;&#xC18D; &#xD558; &#xAC8C; &#xC900;&#xC218; &#xBCF4;&#xB2E4; &#xCCB4; &#xC678;&#xB85C; &#xC27D;&#xAC8C; &#xCC28;&#xBCC4;&#xD654; &#xB41C; &#xB354;. &#xCC9C;&#xCC9C;&#xD788; &#xC811;&#xCC29; &#xC140; (SAC) &#xC778;&#xAD6C; &#xB610;&#xD55C; &#xC0B0;&#xD654; &#xC5FC;&#xC99D; &#xC2A4;&#xD2B8;&#xB808;&#xC2A4;&#xC758; &#xC870;&#xAC74;&#xC744; &#xC2DC;&#xBBAC;&#xB808;&#xC774;&#xC158; &#xD558;&#xB294; &#xC6B4;&#xB3D9; &#xCCB4; &#xC678; &#xBD84;&#xC11D; &#xC2E4;&#xD5D8;&#xC5D0;&#xC11C; RAC &#xC778;&#xAD6C; &#xBCF4;&#xB2E4; &#xB354; &#xC0B4;&#xC544; &#xB0AC;&#xB2E4;. &#xC2EC;&#xADFC; &#xACBD;&#xC0C9; (MI)&#xC758; &#xCE58;&#xB8CC;&#xC5D0; &#xB300; &#xD55C; &#xD3C9;&#xAC00; Sac&#xC758; intramyocardial &#xC8FC;&#xC0AC;&#xB294; Rac&#xC758; &#xC774;&#xC2DD; &#xBCF4;&#xB2E4; &#xC67C;&#xCABD; &#xC2EC; &#xC2E4; (LV) &#xAC1C;&#xC7A5; &#xBC0F; &#xC218;&#xCD95; echocardiographic &#xC778;&#xB371;&#xC2A4;&#xB97C; &#xBCF4;&#xB2E4; &#xD6A8;&#xACFC;&#xC801;&#xC73C;&#xB85C; &#xD5A5;&#xC0C1;. Immunohistological &#xBD84;&#xC11D; &#xBC1D;&#xD600; &#xB9C8;&#xC74C; Sac &#xC8FC;&#xC0AC; &#xC2EC;&#xADFC; &#xC12C;&#xC720; &#xC99D; &#xBC0F; &#xACBD;&#xC0C9; vascularization, &#xAE30;&#xC99D;&#xC790; &#xC138;&#xD3EC; &#xC99D;&#xC2DD; &#xBC0F; &#xC0DD; cardiomyocyte &#xC0DD;&#xC874;&#xACFC; &#xD655;&#xC0B0; RAC &#xCDE8;&#xAE09; &#xB9C8;&#xC74C;&#xC5D0; &#xBE44;&#xD574; &#xC99D;&#xAC00; &#xAC10;&#xC18C;&#xB97C; &#xD45C;&#xC2DC; &#xD569;&#xB2C8;&#xB2E4;. &#xACB0;&#xB860;&#xC801;&#xC73C;&#xB85C;, &#xC774;&#xB7EC;&#xD55C; &#xACB0;&#xACFC; &#xC131;&#xC778; &#xC778;&#xAC04;&#xC758; &#xACE8;&#xACA9; &#xADFC;&#xC721; &#xD30C;&#xC0DD; &#xB41C; &#xC140;&#xC740; Rac&#xB97C; &#xB2A5;&#xAC00; &#xD558;&#xB294; Sac&#xC640; &#xD568;&#xAED8; &#xC2EC;&#xC7A5; &#xC774;&#xC2DD; &#xD6C4; &#xC2EC;&#xC7A5; &#xAE30;&#xB2A5;&#xC744; &#xAC15;&#xD654; &#xD558;&#xB294; &#xAC83;&#xC5D0; &#xB300; &#xD55C; &#xADF8;&#xB4E4;&#xC758; &#xD6A8; &#xD5D8;&#xC5D0; &#xAD00;&#xD574;&#xC11C;&#xB294; &#xAE30;&#xBCF8;&#xC801;&#xC73C;&#xB85C; &#xC720;&#xD615;&#xC774; &#xB2E4;&#xB978; &#xAC83;&#xC774; &#xC88B;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC778;&#xAC04;&#xC758; &#xACE8;&#xACA9; &#xADFC; &#xC138;&#xD3EC; &#xACA9;&#xB9AC; &#xBC0F; &#xD5A5;&#xC0C1; &#xB41C; &#xC2A4;&#xD2B8;&#xB808;&#xC2A4; &#xC800;&#xD56D; &#xD5C8; &#xD608; &#xC131; &#xC2EC; &#xD63C;&#xC758; &#xAE30;&#xB2A5;&#xC744; &#xAC1C;&#xC120; &#xD55C; &#xD6C4; &#xB290;&#xB9B0; &#xC811;&#xCC29; &#xC18D;&#xB3C4;.

La identificaci&#xF3;n de las c&#xE9;lulas que est&#xE1;n dotados de la m&#xE1;xima potencia podr&#xED;a ser cr&#xED;tica para el &#xE9;xito cl&#xED;nico de terapias basadas en c&#xE9;lulas. Hemos investigado si las c&#xE9;lulas con una mayor eficacia de la terapia celular cardiaca podr&#xED;a enriquecerse de los adultos m&#xFA;sculo esquel&#xE9;tico humano sobre la base de sus propiedades de adherencia a los frascos de cultivo de tejidos despu&#xE9;s de la disociaci&#xF3;n del tejido. Las c&#xE9;lulas que se adhiere poco a poco muestran una mayor pureza miog&#xE9;nica y m&#xE1;s f&#xE1;cilmente diferenciadas en miotubos in vitro que las c&#xE9;lulas se adhieren r&#xE1;pidamente (CCR). La celda poco a poco la adhesi&#xF3;n (SAC) de la poblaci&#xF3;n tambi&#xE9;n sobrevivi&#xF3; mejor que la poblaci&#xF3;n RAC en cin&#xE9;tica en ensayos in vitro que simulan las condiciones de estr&#xE9;s oxidativo e inflamatorio. Cuando se evalu&#xF3; para el tratamiento de un infarto de miocardio (IAM), la inyecci&#xF3;n intramioc&#xE1;rdica de las ZEC con mayor eficacia mejor&#xF3; los &#xED;ndices ecocardiogr&#xE1;ficos de ventr&#xED;culo izquierdo (VI) y la contractilidad de remodelaci&#xF3;n que el trasplante de los CCR. El an&#xE1;lisis inmunohistoqu&#xED;mico revel&#xF3; que los corazones inyectados con ZEC muestra una reducci&#xF3;n en la fibrosis del miocardio y un aumento de la vascularizaci&#xF3;n del infarto, la proliferaci&#xF3;n de c&#xE9;lulas de donantes, y la supervivencia y proliferaci&#xF3;n de cardiomiocitos end&#xF3;gena en comparaci&#xF3;n con los corazones CCR tratados. En conclusi&#xF3;n, estos resultados sugieren que los adultos humanos esquel&#xE9;ticos derivados de las c&#xE9;lulas musculares son intr&#xED;nsecamente heterog&#xE9;neos con respecto a su eficacia para mejorar la funci&#xF3;n card&#xED;aca despu&#xE9;s de la implantaci&#xF3;n card&#xED;aca, con ZEC superando los CCR.

Humanos c&#xE9;lulas del m&#xFA;sculo esquel&#xE9;tico con una tasa de adhesi&#xF3;n lento despu&#xE9;s de un aislamiento y la resistencia a la tensi&#xF3;n mejorada mejorar la funci&#xF3;n de los corazones isqu&#xE9;micos

Mesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic cells for regenerative medicine related to osteoarticular, muscular, vascular and inflammatory diseases, although these cells remain heterogeneous and necessitate a better biological characterization. We and others recently described that MSC originate from two types of perivascular cells, namely pericytes and adventitial cells and contain the in situ counterpart of MSC in developing and adult human organs, which can be prospectively purified using well defined cell surface markers. Pericytes encircle endothelial cells of capillaries and microvessels and express the adhesion molecule CD146 and the PDGFRβ, but lack endothelial and haematopoietic markers such as CD34, CD31, vWF (von Willebrand factor), the ligand for Ulex europaeus 1 (UEA1) and CD45 respectively. The proteoglycan NG2 is a pericyte marker exclusively associated with the arterial system. Besides its expression in smooth muscle cells, smooth muscle actin (αSMA) is also detected in subsets of pericytes. Adventitial cells surround the largest vessels and, opposite to pericytes, are not closely associated to endothelial cells. Adventitial cells express CD34 and lack αSMA and all endothelial and haematopoietic cell markers, as for pericytes. Altogether, pericytes and adventitial perivascular cells express in situ and in culture markers of MSC and display capacities to differentiate towards osteogenic, adipogenic and chondrogenic cell lineages. Importantly, adventitial cells can differentiate into pericyte-like cells under inductive conditions in vitro. Altogether, using purified perivascular cells instead of MSC may bring higher benefits to regenerative medicine, including the possibility, for the first time, to use these cells uncultured.

Perivascular cells for regenerative medicine.

The presence of mesenchymal stem cells (MSCs) has been described in various organs. Pericytes possess a multilineage differentiation potential and have been suggested to be one of the developmental sources for MSCs. In human liver, pericytes have not been defined. Here, we describe the identification, purification, and characterization of pericytes in human adult and fetal liver. Flow cytometry sorting revealed that human adult and fetal liver contains 0.56%±0.81% and 0.45%±0.39% of CD146(+)CD45(-)CD56(-)CD34(-) pericytes, respectively. Of these, 41% (adult) and 30% (fetal) were alkaline phosphatase-positive (ALP(+)). In situ, pericytes were localized around periportal blood vessels and were positive for NG2 and vimentin. Purified pericytes could be cultured extensively and had low population doubling times. Immunofluorescence of cultures demonstrated that cells were positive for pericyte and mesenchymal cell markers CD146, NG2, CD90, CD140b, and vimentin, and negative for endothelial, hematopoietic, stellate, muscle, or liver epithelial cell markers von Willebrand factor, CD31, CD34, CD45, CD144, CD326, CK19, albumin, α-fetoprotein, CYP3A7, glial fibrillary acid protein, MYF5, and Pax7 by gene expression; myogenin and alpha-smooth muscle actin expression were variable. Fluorescence-activated cell sorting analysis of cultures confirmed surface expression of CD146, CD73, CD90, CD10, CD13, CD44, CD105, and ALP and absence of human leukocyte antigen-DR. In vitro differentiation assays demonstrated that cells possessed robust osteogenic and myogenic, but low adipogenic and low chondrogenic differentiation potentials. In functional in vitro assays, cells had typical mesenchymal strong migratory and invasive activity. In conclusion, human adult and fetal livers harbor pericytes that are similar to those found in other organs and are distinct from hepatic stellate cells.

Perivascular mesenchymal progenitors in human fetal and adult liver.

We have previously reported the high regenerative potential of murine muscle-derived stem cells (mMDSCs) that are capable of differentiating into multiple mesodermal cell lineages, including myogenic, endothelial, chondrocytic, and osteoblastic cells. Recently, we described a putative human counterpart of mMDSCs, the myogenic endothelial cells (MECs), in adult human skeletal muscle, which efficiently repair/regenerate the injured and dystrophic skeletal muscle as well as the ischemic heart in animal disease models. Nevertheless it remained unclear whether human MECs, at the clonal level, preserve mMDSC-like chondrogenic and osteogenic potentials and classic stem cell characteristics including high proliferation and resistance to stress. Herein, we demonstrated that MECs, sorted from fresh postnatal human skeletal muscle biopsies, can be grown clonally and exhibit robust resistance to oxidative stress with no tumorigeneity. MEC clones were capable of differentiating into chondrocytes and osteoblasts under inductive conditions in vitro and participated in cartilage and bone formation in vivo. Additionally, adipogenic and angiogenic potentials of clonal MECs (cMECs) were observed. Overall, our study showed that cMECs not only display typical properties of adult stem cells but also exhibit chondrogenic and osteogenic capacities in vitro and in vivo, suggesting their potential applications in articular cartilage and bone repair/regeneration.

Human myogenic endothelial cells exhibit chondrogenic and osteogenic potentials at the clonal level.

We previously reported that mechanical stimulation increased the effectiveness of muscle-derived stem cells (MDSCs) for tissue repair. The objective of this study was to determine the importance of vascular endothelial growth factor (VEGF) on mechanically stimulated MDSCs in a murine model of muscle regeneration.

Beneficial effect of mechanical stimulation on the regenerative potential of muscle-derived stem cells is lost by inhibiting vascular endothelial growth factor.

Mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.

Cellular kinetics of perivascular MSC precursors.

To understand the role, if any, played by pericytes in the regulation of newly formed vessels during angiogenesis. In this study, we investigate whether pericytes regulate the number of nascent endothelial tubes.

ArticleTotal : 2	Year
Publication title Cited by 21	2014
Publication title Cited by 7	2016

Article	Year
Human skeletal muscle cells with a slow adhesion rate after isolation and an enhanced stress resistance improve function of ischemic hearts. Molecular therapy : the journal of the American Society of Gene Therapy\| PubMed ID: 22068427	2012
Perivascular cells for regenerative medicine. Journal of cellular and molecular medicine\| PubMed ID: 22882758	2012
Perivascular mesenchymal progenitors in human fetal and adult liver. Stem cells and development\| PubMed ID: 22931482	2012
Human myogenic endothelial cells exhibit chondrogenic and osteogenic potentials at the clonal level. Journal of orthopaedic research : official publication of the Orthopaedic Research Society\| PubMed ID: 23553740	2013
Beneficial effect of mechanical stimulation on the regenerative potential of muscle-derived stem cells is lost by inhibiting vascular endothelial growth factor. Arteriosclerosis, thrombosis, and vascular biology\| PubMed ID: 23723372	2013
Cellular kinetics of perivascular MSC precursors. Stem cells international\| PubMed ID: 24023546	2013
Pericyte regulation of vascular remodeling through the CXC receptor 3. Arteriosclerosis, thrombosis, and vascular biology\| PubMed ID: 24135023	2013

William C.W. Chen

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