chemical-reversion-conventional-human-pluripotent-stem-cells-to-naive

Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Na&#239;ve-like State with Improved Multilineage Differentiation Potency

Na&#239;ve human pluripotent stem cells (N-hPSC) with improved functionality may have a wide impact in regenerative medicine. The goal of this protocol is ...

Johns Hopkins School of Medicine

&#x8840;&#x7BA1;&#x5468;&#x56F4;&#x591A;&#x80FD;&#x5E72;&#x95F4;&#x5145;&#x8D28;&#x7956;&#x7EC6;&#x80DE;&#x5B58;&#x5728;&#x4E8E;&#x5404;&#x79CD;&#x7EC4;&#x7EC7;&#xFF0C;&#x5305;&#x62EC;&#x80CE;&#x76D8;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#xFF0C;&#x6211;&#x4EEC;&#x5EFA;&#x8BAE;&#x672C;&#x80CE;&#x76D8;&#x7EC4;&#x7EC7;&#x4E2D;&#x7684;&#x4E30;&#x5BCC;&#x8840;&#x7BA1;&#x53EF;&#x4EE5;&#x4F5C;&#x4E3A;&#x6E90;&#x7684;&#x6210;&#x808C;&#x7EC6;&#x80DE;&#x518D;&#x751F;&#x9AA8;&#x9ABC;&#x808C;&#x3002;&#x5165; SCID/mdx &#x9F20;&#xFF0C;&#x5176;&#x4E2D;&#x4ED6;&#x4EEC;&#x53C2;&#x52A0;&#x808C;&#x8089;&#x518D;&#x751F;&#x7684;&#x751F;&#x4EA7; myofibers &#x8868;&#x793A;&#x4EBA;&#x7C7B;&#x6297;&#x808C;&#x840E;&#x7F29;&#x86CB;&#x767D;&#x548C;&#x8840;&#x5F71;&#x7684;&#x8153;&#x80A0;&#x808C;&#x808C;&#x8089;&#x9996;&#x5148;&#x539F;&#x5C01;&#x4E0D;&#x52A8;&#x5730;&#x79FB;&#x690D;&#x89E3;&#x5256;&#x4ECE; mid-gestation &#x4EBA;&#x7C7B;&#x80CE;&#x76D8;&#x7ED2;&#x6BDB;&#x3002;&#x5728;&#x4F53;&#x5916;&#x80CE;&#x76D8;&#x7ED2;&#x6BDB;&#x91CA;&#x653E;&#x8868;&#x793A;&#x9AA8;&#x9AD3;&#x95F4;&#x5145;&#x8D28;&#x5E72;&#x7EC6;&#x80DE;&#x6807;&#x8BB0;&#x7269;&#x7684;&#x5047;&#x5B9A;&#x5468;&#x56F4;&#x8D77;&#x6E90; CD146 + CD34&#x207B;CD45&#x207B;CD56&#x207B; &#x7EC6;&#x80DE;&#x8FC5;&#x901F;&#x575A;&#x6301;&#x4E0E;&#x6D04;&#x6E38;&#x3002;CD146 + CD34&#x207B;CD45&#x207B;CD56&#x207B; &#x8840;&#x7BA1;&#x5468;&#x56F4;&#x7EC6;&#x80DE;&#x5206;&#x79BB;&#x548C;&#x51C0;&#x5316;&#x4ECE;&#x80CE;&#x76D8;&#x7ED2;&#x6BDB;&#x7684;&#x6D41;&#x6D41;&#x5F0F;&#x7EC6;&#x80DE;&#x4EEA;&#x662F;&#x5728;&#x6587;&#x5316;&#x4E2D;&#xFF0C;&#x786E;&#x5B9E;&#x975E;&#x5E38;&#x808C;&#x548C;&#x751F;&#x6210;&#x6297;&#x808C;&#x840E;&#x7F29;&#x86CB;&#x767D;&#x6297;&#x4F53;&#x9633;&#x6027; myofibers&#xFF0C;&#x4ED6;&#x4EEC;&#x664B;&#x5347;&#x5230; SCID/mdx &#x9F20;&#x6807;&#x808C;&#x8089;&#x79FB;&#x690D;&#x672F;&#x540E;&#x8840;&#x7BA1;&#x751F;&#x6210;&#x3002;&#x8FD9;&#x4E9B;&#x610F;&#x89C1;&#x786E;&#x8BA4;&#x95F4;&#x5145;&#x8D28;&#x7956;&#x7EC6;&#x80DE;&#x5728;&#x4EBA;&#x4F53;&#x8840;&#x7BA1;&#x58C1;&#x5185;&#x7684;&#x5B58;&#x5728;&#xFF0C;&#x5E76;&#x8868;&#x660E;&#x4E30;&#x5BCC;&#x5E26;&#x8840;&#x7BA1;&#x8482;&#x7684;&#x4EBA;&#x7C7B;&#x80CE;&#x76D8;&#x8840;&#x7BA1;&#x5468;&#x56F4;&#x808C;&#x7EC6;&#x80DE;&#x80FD;&#x591F;&#x5728;&#x8425;&#x517B;&#x4E0D;&#x826F;&#x6027;&#x808C;&#x5185;&#x8FC1;&#x79FB;&#xFF0C;&#x5E76;&#x91CD;&#x65B0;&#x751F;&#x6210; myofibers &#x7684;&#x4E30;&#x5BCC;&#x6765;&#x6E90;&#x3002;

&#x4EBA;&#x4F53;&#x808C;&#x8089;&#x518D;&#x751F;&#x7684;&#x80CE;&#x76D8;&#x8840;&#x7BA1;&#x5468;&#x56F4;&#x7EC6;&#x80DE;&#x3002;

Perivascular multipotent mesenchymal progenitors exist in a variety of tissues, including the placenta. Here, we suggest that the abundant vasculature present in the human placenta can serve as a source of myogenic cells to regenerate skeletal muscle. Chorionic villi dissected from the mid-gestation human placenta were first transplanted intact into the gastrocnemius muscles of SCID/mdx mice, where they participated in muscle regeneration by producing myofibers expressing human dystrophin and spectrin. In vitro-cultured placental villi released rapidly adhering and migratory CD146+CD34â»CD45â»CD56â» cells of putative perivascular origin that expressed mesenchymal stem cell markers. CD146+CD34â»CD45â»CD56â» perivascular cells isolated and purified from the placental villi by flow cytometry were indeed highly myogenic in culture, and generated dystrophin-positive myofibers, and they promoted angiogenesis after transplantation into SCID/mdx mouse muscles. These observations confirm the existence of mesenchymal progenitor cells within the walls of human blood vessels, and suggest that the richly vascularized human placenta is an abundant source of perivascular myogenic cells able to migrate within dystrophic muscle and regenerate myofibers.

Placental perivascular cells for human muscle regeneration.

P&#xE9;rivasculaires multipotentes m&#xE9;senchymateuses prog&#xE9;nitrices existent dans une vari&#xE9;t&#xE9; de tissus, y compris le placenta. Ici, nous sugg&#xE9;rons que le pr&#xE9;sent syst&#xE8;me vasculaire abondante dans le placenta humain peut servir comme une source de cellules myog&#xE9;niques pour r&#xE9;g&#xE9;n&#xE9;rer le muscle squelettique. Villosit&#xE9;s choriales diss&#xE9;qu&#xE9;s &#xE0; partir du placenta &#xE0; mi-gestation humaine ont d&#x26;#39;abord &#xE9;t&#xE9; transplant&#xE9; intact dans les muscles jumeaux de SCID / mdx souris, o&#xF9; ils ont particip&#xE9; &#xE0; la r&#xE9;g&#xE9;n&#xE9;ration du muscle par myofibres producteurs exprimant la dystrophine humaine et la spectrine. In vitro-culture villosit&#xE9;s placentaires lib&#xE9;r&#xE9; rapidement adh&#xE9;rents et migrateurs CD146 + CD34 CD45 &#x207B; &#x207B; &#x207B; CD56 des cellules d&#x26;#39;origine p&#xE9;rivasculaire putatif qui a exprim&#xE9; marqueurs des cellules souches m&#xE9;senchymateuses. CD146 + CD34 CD45 &#x207B; &#x207B; &#x207B; CD56 des cellules p&#xE9;rivasculaires isol&#xE9;s et purifi&#xE9;s &#xE0; partir des villosit&#xE9;s placentaires par cytom&#xE9;trie de flux ont &#xE9;t&#xE9; en effet tr&#xE8;s myog&#xE9;nique dans la culture, et a g&#xE9;n&#xE9;r&#xE9; la dystrophine-positives myofibres, et ils ont favoris&#xE9; l&#x26;#39;angiogen&#xE8;se apr&#xE8;s la transplantation dans les muscles de souris SCID / mdx. Ces observations confirment l&#x26;#39;existence de cellules souches m&#xE9;senchymateuses dans les parois des vaisseaux sanguins de l&#x26;#39;homme, et sugg&#xE8;rent que le placenta humain richement vascularis&#xE9;e est une source abondante de cellules myog&#xE9;niques p&#xE9;rivasculaires capables de migrer &#xE0; l&#x26;#39;int&#xE9;rieur du muscle dystrophique et la r&#xE9;g&#xE9;n&#xE9;ration des fibres musculaires.

Placentaires cellules p&#xE9;rivasculaires pour la r&#xE9;g&#xE9;n&#xE9;ration des muscles humains

Perivaskul&auml;ren multipotenten Mesenchymale Vorl&auml;uferzellen vorhanden in einer Vielzahl von Geweben, einschlie&szlig;lich der Plazenta. Hier empfehlen wir die reichlich Gef&auml;&szlig;system in der menschlichen Plazenta vorhanden als eine Quelle von myogener Zellen Regenerieren der Skelettmuskulatur dienen kann. Chorionzotten, die von der mid-gestation menschlichen Plazenta seziert wurden zun&auml;chst intakt in die Gastrocnemius Muskeln SCID/Mdx-M&auml;use, transplantiert wo sie bei Muskel-Regeneration nahmen durch die Herstellung von Myofibers, die menschliche Dystrophin und Spektrin auszudr&uuml;cken. In Vitro kultiviert Plazenta Zotten ver&ouml;ffentlicht rasch haftende und wandernde CD146 + CD34&#x207B;CD45&#x207B;CD56&#x207B; Zellen vermeintliche perivaskul&auml;ren Ursprungs, die mesenchymalen Stammzell-Marker ausgedr&uuml;ckt. CD146 + CD34&#x207B;CD45&#x207B;CD56&#x207B; perivaskul&auml;ren Zellen isoliert und gereinigt aus der Plazenta Zotten von Flow Cytometry waren in der Tat sehr myogener in Kultur, generiert Dystrophin-Positive Myofibers und f&ouml;rderten sie Angiogenesis nach der Transplantation in SCID/Mdx Maus Muskeln. Diese Beobachtungen best&auml;tigen die Existenz von mesenchymalen Vorl&auml;uferzellen innerhalb der Mauern der menschlichen Blutgef&auml;&szlig;e, und schlagen vor, da&szlig; die reich gef&auml;&szlig;reichen menschliche Plazenta ist eine reiche Quelle der perivaskul&auml;ren myogener Zellen migrieren innerhalb dystrophische Muskeln und Myofibers zu regenerieren k&ouml;nnen.

Plazenta perivaskul&auml;ren Zellen menschlichen Muskel-Regeneration.

Progenitori mesenchimali multipotenti perivascolare esistono in una variet&agrave; di tessuti, tra cui la placenta. Qui, suggeriamo che la vascolarizzazione abbondante presente nella placenta umana pu&ograve; servire come fonte di cellule miogena rigenerare i muscoli scheletrici. Villi coriali sezionati da placenta umana mid-gestation in primo luogo sono stati trapiantati intatto in muscoli gastrocnemio di topi SCID/mdx, dove hanno partecipato nella rigenerazione muscolare producendo myofibers esprimendo spettrina e distrofina umana. Nei villi placentari coltivate in vitro rilasciato rapidamente aderente e migratorie CD146 + CD34&#x207B;CD45&#x207B;CD56&#x207B; cellule di origine putativo perivascolare che espressi marcatori delle cellule staminali mesenchimali. CD146 + CD34&#x207B;CD45&#x207B;CD56&#x207B; perivascolari cellule isolate e purificate dalle villi placentari di flusso cytometry erano infatti altamente miogena nella cultura e generato myofibers distrofina-positivi, e hanno promosso l&#39;angiogenesi dopo trapianto in muscoli topo SCID/mdx. Queste osservazioni confermano l&#39;esistenza di cellule progenitrici mesenchimali entro le pareti dei vasi sanguigni umani e suggeriscono che la placenta umana riccamente vascolarizzata &egrave; un&#39;abbondante fonte di perivascolare miogena cellule in grado di migrare all&#39;interno distrofica muscolare e rigenerare myofibers.

Cellule perivascolari placentare per rigenerazione muscolare umana.

&#x8840;&#x7BA1;&#x5468;&#x56F2;&#x306E;&#x591A;&#x80FD;&#x6027;&#x9593;&#x8449;&#x7CFB;&#x524D;&#x99C6;&#x7D30;&#x80DE;&#x306F;&#x3001;&#x80CE;&#x76E4;&#x3092;&#x542B;&#x3080;&#x69D8;&#x3005;&#x306A;&#x7D44;&#x7E54;&#x306B;&#x5B58;&#x5728;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F;&#x3001;&#x30D2;&#x30C8;&#x80CE;&#x76E4;&#x306B;&#x8C4A;&#x5BCC;&#x306A;&#x8840;&#x7BA1;&#x304C;&#x5B58;&#x5728;&#x3059;&#x308B;&#x9AA8;&#x683C;&#x7B4B;&#x3092;&#x518D;&#x751F;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x7B4B;&#x7D30;&#x80DE;&#x306E;&#x4F9B;&#x7D66;&#x6E90;&#x3068;&#x3057;&#x3066;&#x6A5F;&#x80FD;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;&#x598A;&#x5A20;&#x4E2D;&#x671F;&#x30D2;&#x30C8;&#x80CE;&#x76E4;&#x304B;&#x3089;&#x89E3;&#x5256;&#x7D68;&#x6BDB;&#x306F;&#x3001;&#x6700;&#x521D;&#x306B;&#x3001;&#x5F7C;&#x3089;&#x304C;&#x4EBA;&#x9593;&#x306E;&#x30B8;&#x30B9;&#x30C8;&#x30ED;&#x30D5;&#x30A3;&#x30F3;&#x3068;&#x30B9;&#x30DA;&#x30AF;&#x30C8;&#x30EA;&#x30F3;&#x3092;&#x767A;&#x73FE;&#x3057;&#x3066;&#x751F;&#x6210;&#x3059;&#x308B;&#x7DDA;&#x7DAD;&#x306B;&#x3088;&#x3063;&#x3066;&#x7B4B;&#x8089;&#x306E;&#x518D;&#x751F;&#x306B;&#x53C2;&#x52A0;&#x3057;&#x305F;SCID / mdx&#x30DE;&#x30A6;&#x30B9;&#x306E;&#x8153;&#x8179;&#x7B4B;&#x306B;&#x305D;&#x306E;&#x307E;&#x307E;&#x79FB;&#x690D;&#x3057;&#x305F;&#x3002; in vitro&#x3067;&#x57F9;&#x990A;&#x3057;&#x305F;&#x80CE;&#x76E4;&#x306E;&#x7D68;&#x6BDB;&#x306F;&#x3001;&#x6025;&#x901F;&#x306B;&#x4ED8;&#x7740;&#x3057;&#x3001;&#x6E21;&#x308A;&#x9CE5;&#x306E;CD146 + CD34 CD45&#x207B;&#x207B;&#x207B;CD56&#x9593;&#x8449;&#x7CFB;&#x5E79;&#x7D30;&#x80DE;&#x30DE;&#x30FC;&#x30AB;&#x30FC;&#x3092;&#x767A;&#x73FE;&#x63A8;&#x5B9A;&#x8840;&#x7BA1;&#x7531;&#x6765;&#x306E;&#x7D30;&#x80DE;&#x3002;&#x30EA;&#x30EA;&#x30FC;&#x30B9;&#x30D5;&#x30ED;&#x30FC;&#x30B5;&#x30A4;&#x30C8;&#x30E1;&#x30C8;&#x30EA;&#x30FC;&#x306B;&#x3088;&#x308B;&#x80CE;&#x76E4;&#x7D68;&#x6BDB;&#x304B;&#x3089;&#x5358;&#x96E2;&#x3055;&#x308C;&#x3001;&#x7CBE;&#x88FD;&#x3055;&#x308C;&#x305F;CD146 + CD34&#x207B;CD45&#x207B;CD56&#x207B;&#x8840;&#x7BA1;&#x5468;&#x56F2;&#x7D30;&#x80DE;&#x306F;&#x3001;&#x57F9;&#x990A;&#x4E2D;&#x306E;&#x5B9F;&#x969B;&#x306B;&#x975E;&#x5E38;&#x306B;&#x7B4B;&#x305F;&#x3057;&#x3001;&#x30B8;&#x30B9;&#x30C8;&#x30ED;&#x30D5;&#x30A3;&#x30F3;&#x967D;&#x6027;&#x7DDA;&#x7DAD;&#x3092;&#x751F;&#x6210;&#x3057;&#x3001;&#x305D;&#x3057;&#x3066;&#x3001;&#x5F7C;&#x3089;&#x306F;SCID / mdx&#x30DE;&#x30A6;&#x30B9;&#x306E;&#x7B4B;&#x8089;&#x306B;&#x79FB;&#x690D;&#x5F8C;&#x306E;&#x8840;&#x7BA1;&#x65B0;&#x751F;&#x3092;&#x4FC3;&#x9032;&#x3057;&#x305F;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x89B3;&#x200B;&#x200B;&#x5BDF;&#x306F;&#x3001;&#x4EBA;&#x9593;&#x306E;&#x8840;&#x7BA1;&#x306E;&#x58C1;&#x5185;&#x306E;&#x9593;&#x8449;&#x7CFB;&#x524D;&#x99C6;&#x7D30;&#x80DE;&#x306E;&#x5B58;&#x5728;&#x3092;&#x78BA;&#x8A8D;&#x3057;&#x3001;&#x8C4A;&#x304B;&#x306A;&#x8840;&#x7BA1;&#x30D2;&#x30C8;&#x80CE;&#x76E4;&#x304C;&#x30B8;&#x30B9;&#x30C8;&#x30ED;&#x30D5;&#x30A3;&#x30FC;&#x7B4B;&#x304A;&#x3088;&#x3073;&#x518D;&#x751F;&#x6210;&#x306E;&#x7B4B;&#x7DDA;&#x7DAD;&#x5185;&#x306B;&#x79FB;&#x884C;&#x3059;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x8840;&#x7BA1;&#x7B4B;&#x7D30;&#x80DE;&#x306E;&#x8C4A;&#x5BCC;&#x306A;&#x4F9B;&#x7D66;&#x6E90;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;

&#x4EBA;&#x9593;&#x306E;&#x7B4B;&#x8089;&#x306E;&#x518D;&#x751F;&#x306E;&#x305F;&#x3081;&#x306B;&#x80CE;&#x76E4;&#x306E;&#x8840;&#x7BA1;&#x5468;&#x56F2;&#x7D30;&#x80DE;

Perivascular multipotent &#xC5FD; progenitors &#xC870;&#xC9C1;, &#xD0DC; &#xBC18; &#xB4F1;&#xC758; &#xB2E4;&#xC591; &#xD55C; &#xC874;&#xC7AC;. &#xC5EC;&#xAE30;, &#xC778;&#xAC04;&#xC758; &#xD0DC; &#xBC18;&#xC5D0; &#xD48D;&#xBD80;&#xD55C; &#xD608;&#xAD00; &#xACE8;&#xACA9; &#xADFC;&#xC721; &#xC7AC;&#xC0DD;&#xC131; myogenic &#xC140;&#xC758; &#xC6D0;&#xBCF8;&#xC73C;&#xB85C; &#xC0AC;&#xC6A9;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4; &#xD558;&#xB294; &#xAC83;&#xC774; &#xC88B;&#xC2B5;&#xB2C8;&#xB2E4;. Mid-gestation &#xC778;&#xAC04;&#xC758; &#xD0DC; &#xBC18;&#xC5D0;&#xC11C; &#xD574; &#xBD80; &#xC735; villi &#xCC98;&#xC74C; SCID/mdx &#xC950;, &#xADF8;&#xB4E4;&#xC740; &#xC778;&#xAC04;&#xC758; dystrophin spectrin &#xD45C;&#xD604; myofibers&#xB97C; &#xC0DD;&#xC0B0; &#xD558; &#xC5EC; &#xADFC;&#xC721; &#xC7AC;&#xC0DD;&#xC131;&#xC5D0; &#xCC38;&#xAC00; gastrocnemius &#xADFC;&#xC721;&#xC5D0; &#xADF8;&#xB300;&#xB85C; &#xC774;&#xC2DD; &#xD588;&#xB2E4;. Placental villi &#xCCB4; &#xC678; &#xBC30;&#xC591; &#xC911;&#xAC04; &#xC5FD; &#xC904;&#xAE30; &#xC138;&#xD3EC; &#xD45C;&#xC2DD; &#xD45C;&#xC2DC; &#xC0C1; perivascular &#xAE30;&#xC6D0;&#xC758; &#xC2E0;&#xC18D; &#xD558; &#xAC8C; &#xC811;&#xCC29; &#xD558; &#xACE0; &#xCCA0;&#xC0C8; CD146 + CD34&#x207B;CD45&#x207B;CD56&#x207B; &#xC140;&#xC744; &#xBC1C;&#xD45C; &#xD588;&#xB2E4;. CD146 + CD34&#x207B;CD45&#x207B;CD56&#x207B; perivascular &#xC138;&#xD3EC; &#xACA9;&#xB9AC; &#xADF8;&#xB9AC;&#xACE0; &#xC815;&#xD654; &#xD750;&#xB984;&#xC5D0; &#xC758;&#xD574; placental villi&#xC5D0;&#xC11C; cytometry &#xD588;&#xB2E4; &#xC2E4;&#xC81C;&#xB85C; &#xB192;&#xC740; &#xBB38;&#xD654;, myogenic&#xC640; dystrophin &#xC591;&#xC131; myofibers &#xC0DD;&#xC131; SCID/mdx &#xB9C8;&#xC6B0;&#xC2A4; &#xADFC;&#xC721;&#xC5D0; &#xC774;&#xC2DD; &#xD6C4; &#xC2E0;&#xC0DD;&#xC744; &#xC2B9;&#xC9C4;. &#xC774;&#xB7EC;&#xD55C; &#xAD00;&#xCE21; &#xC778;&#xAC04;&#xC758; &#xD608;&#xAD00; &#xBCBD; &#xB0B4; &#xC5FD; &#xC870;&#xC0C1; &#xC138;&#xD3EC;&#xC758; &#xC874;&#xC7AC;&#xB97C; &#xD655;&#xC778; &#xD558; &#xACE0; &#xD48D;&#xBD80;&#xD55C; vascularized &#xC778;&#xAC04;&#xC758; &#xD0DC; &#xBC18; &#xD48D;&#xBD80;&#xD55C; &#xC6D0;&#xCC9C;&#xC774; perivascular myogenic &#xC140; dystrophic &#xADFC;&#xC721; &#xB0B4;&#xC5D0;&#xC11C; &#xB9C8;&#xC774;&#xADF8;&#xB808;&#xC774;&#xC158;&#xD560; myofibers&#xB97C; &#xB2E4;&#xC2DC; &#xC0DD;&#xC131; &#xD558;&#xB294; &#xAC83;&#xC774; &#xC88B;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC778;&#xAC04;&#xC758; &#xADFC;&#xC721; &#xC7AC;&#xC0DD; &#xD0DC; &#xBC18; perivascular &#xC140;&#xC785;&#xB2C8;&#xB2E4;.

Perivasculares progenitores mesenquimales multipotentes existir en una variedad de tejidos, incluyendo la placenta. Aqu&#xED;, se sugiere que la presente vasculatura abundante en la placenta humana puede servir como una fuente de c&#xE9;lulas miog&#xE9;nicas para regenerar el m&#xFA;sculo esquel&#xE9;tico. Las vellosidades cori&#xF3;nicas disecados de la placenta humana mitad de la gestaci&#xF3;n fueron trasplantados primera intacto en los m&#xFA;sculos gemelos de SCID / MDX ratones, en los que participaron en la regeneraci&#xF3;n del m&#xFA;sculo por la producci&#xF3;n de fibras musculares que expresan humana distrofina y espectrina. In vitro, cultivo de vellosidades placentarias libera r&#xE1;pidamente adherentes y migratorias CD146 + CD34 CD45 &#x207B; &#x207B; CD56 &#x207B; c&#xE9;lulas de origen supuesta perivascular que expresa marcadores de c&#xE9;lulas madre mesenquimales. CD146 + CD34 &#x207B; CD45 CD56 &#x207B; &#x207B; de las c&#xE9;lulas perivasculares aislados y purificados a partir de las vellosidades placentarias por citometr&#xED;a de flujo eran en realidad altamente miog&#xE9;nica en la cultura, y ha generado positivas de distrofina fibras musculares, y se promueve la angiog&#xE9;nesis tras el trasplante en los m&#xFA;sculos de ratones SCID / MDX. Estas observaciones confirman la existencia de c&#xE9;lulas progenitoras mesenquimales dentro de las paredes de los vasos sangu&#xED;neos humanos, y sugieren que el ricamente vascularizado de la placenta humana es una fuente abundante de c&#xE9;lulas perivasculares miog&#xE9;nicas capaces de migrar dentro del m&#xFA;sculo distr&#xF3;fico y regenerar fibras musculares.

Placenta c&#xE9;lulas perivasculares para la regeneraci&#xF3;n del m&#xFA;sculo humano

Cancer treatment generally relies on tumor ablative techniques that can lead to major functional or disfiguring defects. These post-therapy impairments require the development of safe regenerative therapy strategies during cancer remission. Many current tissue repair approaches exploit paracrine (immunomodulatory, pro-angiogenic, anti-apoptotic and pro-survival effects) or restoring (functional or structural tissue repair) properties of mesenchymal stem/stromal cells (MSC). Yet, a major concern in the application of regenerative therapies during cancer remission remains the possible triggering of cancer recurrence. Tumor relapse implies the persistence of rare subsets of tumor-initiating cancer cells which can escape anti-cancer therapies and lie dormant in specific niches awaiting reactivation via unknown stimuli. Many of the components required for successful regenerative therapy (revascularization, immunosuppression, cellular homing, tissue growth promotion) are also critical for tumor progression and metastasis. While bi-directional crosstalk between tumorigenic cells (especially aggressive cancer cell lines) and MSC (including tumor stroma-resident populations) has been demonstrated in a variety of cancers, the effects of local or systemic MSC delivery for regenerative purposes on persisting cancer cells during remission remain controversial. Both pro- and anti-tumorigenic effects of MSC have been reported in the literature. Our own data using breast cancer clinical isolates have suggested that dormant-like tumor-initiating cells do not respond to MSC signals, unlike actively dividing cancer cells which benefited from the presence of supportive MSC. The secretome of MSC isolated from various tissues may partially diverge, but it includes a core of cytokines (i.e. CCL2, CCL5, IL-6, TGFβ, VEGF), which have been implicated in tumor growth and/or metastasis. This article reviews published models for studying interactions between MSC and cancer cells with a focus on the impact of MSC secretome on cancer cell activity, and discusses the implications for regenerative therapy after cancer. 

Mesenchymal stem cell secretome and regenerative therapy after cancer.

The generation of vascular progenitors (VPs) from human induced pluripotent stem cells (hiPSCs) has great potential for treating vascular disorders such as ischemic retinopathies. However, long-term in vivo engraftment of hiPSC-derived VPs into the retina has not yet been reported. This goal may be limited by the low differentiation yield, greater senescence, and poor proliferation of hiPSC-derived vascular cells. To evaluate the potential of hiPSCs for treating ischemic retinopathies, we generated VPs from a repertoire of viral-integrated and nonintegrated fibroblast and cord blood (CB)-derived hiPSC lines and tested their capacity for homing and engrafting into murine retina in an ischemia-reperfusion model.

Ludovic Zimmerlin

Department of Oncology,
Division of Pediatric Oncology and Institute for Cell Engineering,
Department of Oncology, Division of Pediatric Oncology and Institute for Cell Engineering

Johns Hopkins School of Medicine

Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naïve-like State with Improved Multilineage Differentiation Potency

Ludovic Zimmerlin

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Oncology,Division of Pediatric Oncology and Institute for Cell Engineering,Department of Oncology, Division of Pediatric Oncology and Institute for Cell Engineering

Johns Hopkins School of Medicine

Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naïve-like State with Improved Multilineage Differentiation Potency

Department of Oncology,
Division of Pediatric Oncology and Institute for Cell Engineering,
Department of Oncology, Division of Pediatric Oncology and Institute for Cell Engineering