Harmonic Nanoparticles for Regenerative Research

In this visualized experiment, protocol details are provided for in vitro labeling of human embryonic stem cells (hESC) with second harmonic generation ...

University of Geneva

Skeletal muscle hypertrophy is a result of increased load, such as functional and stretch-overload. Activation of satellite cells and proliferation, differentiation and fusion are required for hypertrophy of overloaded skeletal muscles. On the contrary, a dramatic loss of skeletal muscle mass determines atrophy settings. The epigenetic changes involved in gene regulation at DNA and chromatin level are critical for the opposing phenomena, muscle growth and atrophy. Physiological properties of skeletal muscle tissue play a fundamental role in health and disease since it is the most abundant tissue in mammals. In fact, protein synthesis and degradation are finely modulated to maintain an appropriate muscle mass. When the molecular signaling is altered muscle wasting and weakness occurred, and this happened in most common inherited and acquired disorders such as muscular dystrophies, cachexia, and age-related wasting. To date, there is no accepted treatment to improve muscle size and strength, and these conditions pose a considerable anxiety to patients as well as to public health. Several molecules, including Magic-F1, myostatin inhibitor, IGF, glucocorticoids and microRNAs are currently investigated to interfere positively in the blueprint of skeletal muscle growth and regeneration.

Cellular mechanisms and local progenitor activation to regulate skeletal muscle mass.

Three-dimensional (3D) titanium-6-aluminium-4-vanadium (Ti6Al4V) is a widely used biomaterial for orthopedic prosthesis and dental implants; thanks to its very high-mechanical strength and resistance to corrosion. Human mesenchymal stem cells (hMSCs) and dental pulp stem cells (hDPSCs) are responsible for bone regeneration following colonization of prosthesis or dental implants. Both hMSCs and hDPSCs have lower ability to colonize this biomaterial in comparison with tissue culture-treated plastic. Both hMSCs and hDPSCs show lack of focal adhesion kinase (FAK) activation when grown on Ti6Al4V. This signal is restored in the presence of poly-L-lysine (poly-L-lys). Poly-L-lys has been used as part of organoapatite or together with zinc and calcium ions. Our results suggest that poly-L-lys alone induces FAK activation through β1-INTEGRIN, because the presence of β1-INTEGRIN blocking antibody avoided FAK autophosphorylation. Presence of poly-L-lys also increases expression of osteoblastic differentiation marker genes in hMSCs and hDPSCs grown on Ti6Al4V.

In vitro osteoblastic differentiation of human mesenchymal stem cells and human dental pulp stem cells on poly-L-lysine-treated titanium-6-aluminium-4-vanadium.

&#x4EA7;&#x540E;&#x5FC3;&#x810F;&#x5E72;&#x548C;&#x7956;&#x7EC6;&#x80DE;&#x5FC3;&#x808C;&#xFF0C;&#x6F5C;&#x5728;&#x7684;&#x6CBB;&#x7597;&#x5DE5;&#x5177;&#x4F46;&#x63A7;&#x5236;&#x5FC3;&#x810F;&#x5206;&#x5316;&#x7684;&#x673A;&#x5236;&#x4E86;&#x89E3;&#x751A;&#x5C11;&#x3002;&#x6700;&#x8FD1;&#x7684;&#x5DE5;&#x4F5C;&#x5DF2;&#x4F5C;&#x4E3A;&#x76D1;&#x7BA1;&#x8005;&#x7684;&#x5FC3;&#x810F;&#x548C;&#x9AA8;&#x9ABC;&#x808C;&#x6210;&#x808C;&#x7A81;&#x51FA; microribonucleic &#x9178; (Mirna) &#x53D1;&#x6325;&#x91CD;&#x8981;&#x4F5C;&#x7528;&#x3002;&#x5728;&#x672C;&#x6587;&#x4E2D;&#xFF0C;&#x6211;&#x4EEC;&#x5B64;&#x7ACB;&#x5FC3;&#x810F;&#x7956;&#x7EC6;&#x80DE;&#x4ECE;&#x65B0;&#x751F;&#x513F; &beta;-sarcoglycan (Sgcb)-&#x9F20;&#x6807;&#x5FC3;&#x53D7;&#x6269;&#x5F20;&#x578B;&#x5FC3;&#x808C;&#x75C5;&#xFF0C;&#x5219;&#x4E3A; null&#x3002;&#x610F;&#x5916;&#x7684;&#x662F;&#xFF0C;Sgcb null &#x5FC3;&#x810F;&#x7956;&#x7EC6;&#x80DE;&#x81EA;&#x53D1;&#x5206;&#x5316;&#x4E3A;&#x9AA8;&#x9ABC;&#x808C;&#x7EA4;&#x7EF4;&#x4F53;&#x5916;&#x548C;&#x5F53;&#x79FB;&#x690D;&#x518D;&#x751F;&#x808C;&#x8089;&#x6216;&#x5FC3;&#x808C;&#x6897;&#x6B7B;&#x3002;&#x6F5C;&#x5728;&#x5206;&#x5316;&#x76F8;&#x5173;&#x4E0E;&#x7F3A;&#x4E4F;&#x8868;&#x8FBE;&#x7684;&#x65B0;&#x578B;&#x7C73;&#x5C14;&#xFF0C;miR669q&#xFF0C;&#x548C; miR669a &#x7684;&#x4E0B;&#x8C03;&#x3002;&#x5176;&#x4ED6; Mirna &#x5DF2;&#x77E5;&#x4FC3;&#x8FDB;&#x6210;&#xFF0C;&#x4F46;&#x53EA;&#x6709; miR669a &#x548C; miR669q &#x6CD5;&#x4E0A;&#x6E38;&#x751F;&#x808C;&#x8C03;&#x8282;&#x56E0;&#x5B50;&#xFF0C;&#x901A;&#x8FC7;&#x76F4;&#x63A5;&#x9488;&#x5BF9; MyoD 3&#39; &#x975E;&#x7FFB;&#x8BD1;&#x7684;&#x533A;&#x9632;&#x6B62;&#x6210;&#x808C;&#x808C;&#x3002;&#x8FD9;&#x4E00;&#x53D1;&#x73B0;&#x63ED;&#x793A;&#x4E86;&#x4E2D;&#x7684;&#x4E2D;&#x80DA;&#x5C42;&#x7956;&#x7EC6;&#x80DE;&#x7684;&#x547D;&#x8FD0;&#x9009;&#x62E9;&#x673A;&#x5236;&#x7684;&#x590D;&#x6742;&#x6027;&#x589E;&#x52A0;&#x7684;&#x7EA7;&#x522B;&#xFF0C;&#x5E76;&#x5EFA;&#x8BAE;&#x4F7F;&#x7528;&#x5185;&#x6E90;&#x6027;&#x5FC3;&#x810F;&#x5E72;&#x7EC6;&#x80DE;&#x6CBB;&#x7597;&#x5C06;&#x67D0;&#x4E9B;&#x9057;&#x4F20;&#x75BE;&#x75C5;&#x9700;&#x8981;&#x4E13;&#x95E8;&#x7684;&#x7A0B;&#x5E8F;&#x3002;

miR669a &#x548C; miR669q &#x9632;&#x6B62;&#x808C;&#x8089;&#x5728;&#x4EA7;&#x540E;&#x5FC3;&#x810F;&#x7956;&#x7EC6;&#x80DE;&#x7684;&#x5206;&#x5316;&#x3002;

Postnatal heart stem and progenitor cells are a potential therapeutic tool for cardiomyopathies, but little is known about the mechanisms that control cardiac differentiation. Recent work has highlighted an important role for microribonucleic acids (miRNAs) as regulators of cardiac and skeletal myogenesis. In this paper, we isolated cardiac progenitors from neonatal Î²-sarcoglycan (Sgcb)-null mouse hearts affected by dilated cardiomyopathy. Unexpectedly, Sgcb-null cardiac progenitors spontaneously differentiated into skeletal muscle fibers both in vitro and when transplanted into regenerating muscles or infarcted hearts. Differentiation potential correlated with the absence of expression of a novel miRNA, miR669q, and with down-regulation of miR669a. Other miRNAs are known to promote myogenesis, but only miR669a and miR669q act upstream of myogenic regulatory factors to prevent myogenesis by directly targeting the MyoD 3' untranslated region. This finding reveals an added level of complexity in the mechanism of the fate choice of mesoderm progenitors and suggests that using endogenous cardiac stem cells therapeutically will require specially tailored procedures for certain genetic diseases.

miR669a and miR669q prevent skeletal muscle differentiation in postnatal cardiac progenitors.

Les cellules souches et prog&eacute;nitrices coeur postnatal sont un outil th&eacute;rapeutique potentiel pour les cardiomyopathies, mais peu est connu sur les m&eacute;canismes qui contr&ocirc;lent la diff&eacute;renciation cardiaque. Des travaux r&eacute;cents a mis en &eacute;vidence un r&ocirc;le important pour les acides microribonucleic (miARN) comme r&eacute;gulateurs de la myogen&egrave;se squelettique et cardiaque. Dans cet article, les auteurs ont isol&eacute; des prog&eacute;niteurs cardiaques de n&eacute;onatale &beta;-sarcoglycane (Sgcb)-null coeurs souris affect&eacute;es par une cardiomyopathie dilat&eacute;e. Contre toute attente, prog&eacute;niteurs cardiaques Sgcb null diff&eacute;rencient spontan&eacute;ment dans les fibres musculaires squelettiques in vitro et lorsque transplant&eacute;s dans la r&eacute;g&eacute;n&eacute;ration des muscles ou coeurs infarci. Potentielle de diff&eacute;renciation en corr&eacute;lation avec l&#39;absence d&#39;expression d&#39;un roman miRNA, miR669q et vers le bas-r&egrave;glement des miR669a. Autres miARN est connus pour favoriser la myogen&egrave;se, mais seulement miR669a et miR669q agir en amont des facteurs de r&eacute;gulation myog&eacute;niques pour emp&ecirc;cher la myogen&egrave;se en ciblant directement la MyoD r&eacute;gion 3&#39; non traduite. Ce constat r&eacute;v&egrave;le un niveau suppl&eacute;mentaire de complexit&eacute; dans le m&eacute;canisme du choix sort des prog&eacute;niteurs m&eacute;soderme et sugg&egrave;re en utilisant des cellules souches cardiaques endog&egrave;nes th&eacute;rapeutiquement n&eacute;cessiteront des proc&eacute;dures sp&eacute;cialement adapt&eacute;es pour certaines maladies g&eacute;n&eacute;tiques.

miR669a et miR669q emp&ecirc;chent la diff&eacute;renciation musculaire squelettique en postnatals prog&eacute;niteurs cardiaques.

Postnatale Herzzellen Stamm- und Vorl&auml;uferzellen sind einem potenziellen therapeutischen Hilfsmittel f&uuml;r Kardiomyopathien, aber wenig ist bekannt &uuml;ber die Mechanismen, die kardialen Differenzierung zu steuern. Die j&uuml;ngsten Arbeiten hat eine wichtige Rolle f&uuml;r Microribonucleic S&auml;uren (MiRNAs) als Regler der Herz- und Skelettmuskulatur Myogenese hervorgehoben. In diesem Papier isoliert wir kardiale Vorl&auml;uferzellen von Neugeborenen &beta;-Sarkoglykan (Sgcb)-null-Maus-Herzen von dilatative Kardiomyopathie betroffen. Sgcb-Null kardiale Vorl&auml;uferzellen differenziert unerwartet spontan in skelettartiger Muskel Fasern sowohl in Vitro als auch beim transplantierte in Muskeln oder infarcted Herzen regenerieren. M&ouml;gliche Differenzierung korreliert mit dem Fehlen des Ausdrucks von einer neuartigen MiRNA, miR669q, und mit Herunterregulation miR669a. Andere MiRNAs sind bekannterma&szlig;en Myogenese, sondern nur miR669a und miR669q handeln stromaufw&auml;rts myogener regulatorische Faktoren zu Myogenese durch verhindern, dass direkt den MyoD 3&#39; Untranslatierter Bereich zu f&ouml;rdern. Diese Feststellung zeigt ein zus&auml;tzliches Ma&szlig; an Komplexit&auml;t in den Mechanismus der Schicksal Wahl des Mesoderm Vorl&auml;uferzellen und legt nahe, dass endogene kardiale Stammzellen therapeutisch ma&szlig;geschneiderte Verfahren f&uuml;r bestimmte genetischen Krankheiten ben&ouml;tigt.

miR669a und miR669q verhindern Skelettmuskulatur Differenzierung im postnatalen kardialen Vorl&auml;uferzellen.

Cellule staminali e progenitrici postnatale cuore sono un potenziale strumento terapeutico per cardiomiopatie, ma poco si sa circa i meccanismi che controllano la differenziazione cardiache. Lavoro recente ha evidenziato un ruolo importante per microribonucleic acidi (miRNAs) come regolatori del myogenesis cardiaco e scheletrico. In questo libro, abbiamo isolato cardiaci progenitori da &beta;-sarcoglicano neonatale (Sgcb)-null cuori del mouse affetti da cardiomiopatia dilatativa. Inaspettatamente, progenitori cardiaci Sgcb-null spontaneamente differenziano nelle fibre del muscolo scheletrici sia in vitro che quando trapiantato nel rigenerare i muscoli o cuori aneurismatico. Potenziale di differenziazione correlata con l&#39;assenza di espressione di un romanzo quieto, miR669q e con down-regulation dei miR669a. Altri miRNAs sono noti per promuovere myogenesis, ma solo miR669a e miR669q atto a Monte di miogena fattori normativi al fine di prevenire myogenesis destinati direttamente al MyoD 3&#39; untranslated region. Questa constatazione rivela un ulteriore livello di complessit&agrave; nel meccanismo della scelta destino dei progenitori del mesoderma e suggerisce che utilizzando le cellule staminali cardiache endogene terapeuticamente richiede procedure appositamente su misura per determinate malattie genetiche.

miR669a e miR669q prevenire la differenziazione del muscolo scheletrico in progenitori cardiaci postnatale.

&#x751F;&#x5F8C;&#x5FC3;&#x81D3;&#x5E79;&#x30FB;&#x524D;&#x99C6;&#x7D30;&#x80DE;&#x5FC3;&#x7B4B;&#x75C7;&#x306E;&#x305F;&#x3081;&#x306E;&#x6F5C;&#x5728;&#x7684;&#x306A;&#x6CBB;&#x7642;&#x306E;&#x30C4;&#x30FC;&#x30EB;&#x3067;&#x3059;&#x304C;&#x3001;&#x5FC3;&#x7B4B;&#x5206;&#x5316;&#x5236;&#x5FA1;&#x6A5F;&#x69CB;&#x306B;&#x3064;&#x3044;&#x3066;&#x306F;&#x307B;&#x3068;&#x3093;&#x3069;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x307E;&#x305B;&#x3093;&#x3002;&#x6700;&#x8FD1;&#x306E;&#x4ED5;&#x4E8B; microribonucleic &#x9178; (Mirna) &#x306E;&#x305F;&#x3081;&#x306E;&#x91CD;&#x8981;&#x306A;&#x5F79;&#x5272;&#x306F;&#x5FC3;&#x7B4B;&#x304A;&#x3088;&#x3073;&#x9AA8;&#x683C;&#x7B4B;&#x5F62;&#x6210;&#x306E;&#x8ABF;&#x7BC0;&#x56E0;&#x5B50;&#x3068;&#x3057;&#x3066;&#x5F37;&#x8ABF;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x672C;&#x7A3F;&#x3067;&#x306F;, &#x6211;&#x3005; &#x5FC3;&#x7B4B;&#x524D;&#x99C6;&#x7D30;&#x80DE;&#x65B0;&#x751F;&#x5150; &beta;-sarcoglycan (Sgcb) &#x304B;&#x3089;&#x5206;&#x96E2;&#x3055;&#x308C;&#x305F;-&#x62E1;&#x5F35;&#x578B;&#x5FC3;&#x7B4B;&#x75C7;&#x306B;&#x3088;&#x3063;&#x3066;&#x5F71;&#x97FF;&#x3092;&#x53D7;&#x3051;&#x308B;&#x30DE;&#x30A6;&#x30B9;&#x5FC3;&#x306F; null &#x3092;&#x8FD4;&#x3057;&#x307E;&#x3059;&#x3002;&#x4E88;&#x671F;&#x305B;&#x305A;&#x3001;Sgcb null &#x5FC3;&#x7B4B;&#x524D;&#x99C6;&#x7D30;&#x80DE;&#x9AA8;&#x683C;&#x7B4B;&#x7DDA;&#x7DAD;&#x4E21;&#x65B9;&#x751F;&#x4F53;&#x5916;&#x3067;&#x305D;&#x3057;&#x3066;&#x7B4B;&#x8089;&#x307E;&#x305F;&#x306F;&#x6897;&#x585E;&#x7FA4;&#x306E;&#x5FC3;&#x306E;&#x518D;&#x751F;&#x306B;&#x79FB;&#x690D;&#x3059;&#x308B;&#x3068;&#x304D;&#x306B;&#x81EA;&#x767A;&#x7684;&#x306B;&#x5206;&#x5316;&#x3057;&#x305F;.&#x6F5C;&#x5728;&#x7684;&#x306A;&#x5206;&#x5316; miR669q&#x3001;&#x5C0F;&#x8AAC;&#x306E; miRNA &#x306E;&#x8868;&#x73FE;&#x306E;&#x6B20;&#x5982;&#x3068; miR669a &#x306E;&#x30C0;&#x30A6;&#x30F3;&#x30EC;&#x30AE;&#x30E5;&#x30EC;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x3068;&#x76F8;&#x95A2;&#x3002;&#x4ED6;&#x306E; miRNAs &#x306E;&#x307F; miR669a &#x3068; miR669q &#x4E0A;&#x6D41;&#x306E;&#x884C;&#x70BA;&#x76F4;&#x63A5; MyoD 3&#39; &#x975E;&#x7FFB;&#x8A33;&#x9818;&#x57DF;&#x3092;&#x5BFE;&#x8C61;&#x7B4B;&#x5F62;&#x6210;&#x3092;&#x9632;&#x3050;&#x305F;&#x3081;&#x306B;&#x7B4B;&#x306E;&#x898F;&#x5236;&#x8981;&#x56E0;&#x3067;&#x3059;&#x304C;&#x7B4B;&#x5F62;&#x6210;&#x3092;&#x4FC3;&#x9032;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3053;&#x306E;&#x767A;&#x898B;&#x306F;&#x4E2D;&#x80DA;&#x8449;&#x306E;&#x524D;&#x99C6;&#x7D30;&#x80DE;&#x306E;&#x904B;&#x547D;&#x9078;&#x629E;&#x6A5F;&#x69CB;&#x306B;&#x304A;&#x3051;&#x308B;&#x8907;&#x96D1;&#x3055;&#x306E;&#x8FFD;&#x52A0;&#x30EC;&#x30D9;&#x30EB;&#x3092;&#x660E;&#x3089;&#x304B;&#x306B;&#x3057;&#x3001;&#x5185;&#x56E0;&#x6027;&#x5FC3;&#x7B4B;&#x5E79;&#x7D30;&#x80DE;&#x6CBB;&#x7642;&#x3092;&#x4F7F;&#x7528;&#x3057;&#x3066;&#x7279;&#x5B9A;&#x306E;&#x907A;&#x4F1D;&#x75C5;&#x306E;&#x7279;&#x5225;&#x4ED5;&#x7ACB;&#x3066;&#x306E;&#x30D7;&#x30ED;&#x30B7;&#x30FC;&#x30B8;&#x30E3;&#x3092;&#x8981;&#x6C42;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;

miR669a &#x3068; miR669q &#x751F;&#x5F8C;&#x5FC3;&#x7B4B;&#x524D;&#x99C6;&#x7D30;&#x80DE;&#x306E;&#x9AA8;&#x683C;&#x7B4B;&#x5206;&#x5316;&#x3092;&#x9632;&#x3050;&#x3002;

&#xCD9C;&#xC0DD; &#xD6C4; &#xC2EC;&#xC7A5; &#xC904;&#xAE30;&#xC640; &#xC870;&#xC0C1; &#xC138;&#xD3EC; cardiomyopathies&#xC5D0; &#xB300; &#xD55C; &#xC7A0;&#xC7AC;&#xC801;&#xC778; &#xCE58;&#xB8CC; &#xB3C4;&#xAD6C;&#xB294; &#xD558;&#xC9C0;&#xB9CC; &#xC57D;&#xAC04; &#xC2EC;&#xC7A5; &#xCC28;&#xBCC4;&#xD654;&#xB97C; &#xC81C;&#xC5B4; &#xD558;&#xB294; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC5D0; &#xB300; &#xD55C; &#xC54C;&#xB824;&#xC838; &#xC788;&#xB2E4;. &#xCD5C;&#xADFC; &#xC791;&#xD488; &#xC2EC;&#xC7A5;&#xACFC; &#xACE8;&#xACA9; myogenesis&#xC758; &#xB808; &#xADE4; &#xB808;&#xC774; &#xD130;&#xB85C; microribonucleic &#xC0B0; (miRNAs)&#xC5D0; &#xB300; &#xD55C; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;&#xC744; &#xAC15;&#xC870; &#xD588;&#xB2E4;. &#xC774; &#xB17C;&#xBB38;&#xC5D0;&#xC11C; &#xC6B0;&#xB9AC; &#xC2E0;&#xC0DD;&#xC544; &beta;-sarcoglycan (Sgcb)&#xC5D0;&#xC11C; &#xC2EC;&#xC7A5; progenitors &#xC808;&#xC5F0;-null &#xB9C8;&#xC6B0;&#xC2A4; &#xB9C8;&#xC74C; &#xB3D9; &#xACF5;&#xC774; &#xD655;&#xC7A5; &#xB418;&#xC5B4; &#xC2EC;&#xC7A5; &#xADFC;&#xC721; &#xBCD1; &#xC99D;&#xC5D0; &#xC758;&#xD574; &#xC601;&#xD5A5;&#xC744; &#xBC1B;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC608;&#xAE30;&#xCE58; &#xC54A;&#xAC8C;, Sgcb null &#xC2EC;&#xC7A5; progenitors &#xCCB4; &#xC678;&#xC640; &#xADFC;&#xC721; &#xB610;&#xB294; infarcted &#xB9C8;&#xC74C; &#xC7AC;&#xC0DD;&#xC131;&#xC5D0; &#xC774;&#xC2DD; &#xD558;&#xB294; &#xACBD;&#xC6B0; &#xACE8;&#xACA9; &#xADFC;&#xC721; &#xC12C;&#xC720;&#xC5D0; &#xC790;&#xBC1C;&#xC801;&#xC73C;&#xB85C; &#xCC28;&#xBCC4;&#xD654; &#xB41C;. &#xCC28;&#xBCC4;&#xD654; &#xC7A0;&#xC7AC;&#xC801;&#xC778; &#xB2E4;&#xC6B4; &#xB808; &#xADE4; &#xB808;&#xC774; &#xC158; Mir669a&#xC758; miR669q, &#xC18C;&#xC124; Mirna&#xC758; &#xD45C;&#xD604;&#xC758; &#xBD80;&#xC7AC;&#xC640; &#xC0C1;&#xAD00;. &#xD558;&#xC9C0;&#xB9CC; miR669a &#xBC0F; miR669q &#xD589;&#xB3D9; &#xC0C1;&#xB958; &#xC9C1;&#xC811; MyoD 3&#39; &#xB9DE;&#xC774; &#xC9C0;&#xC5ED; &#xB300;&#xC0C1;&#xC73C;&#xB85C; myogenesis&#xB97C; &#xBC29;&#xC9C0; &#xD558;&#xAE30; &#xC704;&#xD574; myogenic &#xADDC;&#xC81C; &#xC694;&#xC778;&#xC758; myogenesis&#xB97C; &#xD64D;&#xBCF4; &#xD558;&#xB294; &#xB2E4;&#xB978; miRNAs &#xC54C;&#xB824;&#xC838; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC774; &#xCC3E;&#xB294; mesoderm progenitors&#xC758; &#xC6B4;&#xBA85; &#xC120;&#xD0DD;&#xC758; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC5D0;&#xC11C; &#xBCF5;&#xC7A1;&#xC131; &#xC218;&#xC900;&#xC744; &#xCD94;&#xAC00; &#xACC4;&#xC2DC; &#xD558; &#xACE0;&#xB294; &#xD2B9;&#xC815; &#xC720;&#xC804; &#xC9C8;&#xD658;&#xC5D0; &#xB300; &#xD55C; &#xD2B9;&#xC218; &#xB9DE;&#xCDA4;&#xD615;&#xB41C; &#xC808;&#xCC28; &#xD544;&#xC694; therapeutically &#xC0DD; &#xC2EC;&#xC7A5; &#xC904;&#xAE30; &#xC138;&#xD3EC;&#xB97C; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xC81C;&#xC548; &#xD569;&#xB2C8;&#xB2E4;.

miR669a &#xBC0F; miR669q &#xC0B0; &#xD6C4; &#xC2EC;&#xC7A5; progenitors&#xC5D0;&#xC11C; &#xACE8;&#xACA9; &#xADFC;&#xC721; &#xBD84;&#xD654;&#xB97C; &#xBC29;&#xC9C0;.

Las c&eacute;lulas madre y progenitoras coraz&oacute;n postnatal son una herramienta terap&eacute;utica potencial de cardiomiopat&iacute;as, pero poco se sabe sobre los mecanismos que controlan la diferenciaci&oacute;n cardiaca. Trabajo reciente ha puesto de relieve un papel importante de &aacute;cidos microribonucleic (miRNAs) como reguladores de la miog&eacute;nesis card&iacute;aco y esquel&eacute;tico. En este trabajo se aislaron cardiacas progenitores de &beta;-sarcoglycan neonatal (Sgcb)-null corazones rat&oacute;n afectados por miocardiopat&iacute;a dilatada. Inesperadamente, progenitores cardiacas Sgcb nulo espont&aacute;neamente se distinguen en fibras de m&uacute;sculo esquel&eacute;ticas tanto in vitro como cuando trasplant&oacute; en regenerar los m&uacute;sculos o el coraz&oacute;n infartado. Potencial de diferenciaci&oacute;n correlacion&oacute; con la ausencia de expresi&oacute;n de una novela miRNA, miR669q y con regulaci&oacute;n de miR669a. Se conocen otros miRNAs promover miog&eacute;nesis, pero s&oacute;lo miR669a y miR669q acto aguas arriba de factores reguladores miog&eacute;nicos para evitar miog&eacute;nesis dirigi&eacute;ndose directamente a la regi&oacute;n sin traducir MyoD 3&#39;. Este hallazgo revela un nivel adicional de complejidad en el mecanismo de la elecci&oacute;n del destino de progenitores de mesodermo y sugiere que utilizar c&eacute;lulas cardiacas end&oacute;genas terap&eacute;uticamente requerir&aacute; procedimientos adaptados especialmente para ciertas enfermedades gen&eacute;ticas.

miR669a y miR669q evitan la diferenciaci&oacute;n del m&uacute;sculo esquel&eacute;tico en progenitores cardiacas postnatales.

Mice deficient in α-sarcoglycan (Sgca-null mice) develop progressive muscular dystrophy and serve as a model for human limb girdle muscular dystrophy type 2D. Sgca-null mice suffer a more severe myopathy than that of mdx mice, the model for Duchenne muscular dystrophy. This is the opposite of what is observed in humans and the reason for this is unknown. In an attempt to understand the cellular basis of this severe muscular dystrophy, we isolated clonal populations of myogenic progenitor cells (MPCs), the resident postnatal muscle progenitors of dystrophic and wild-type mice. MPCs from Sgca-null mice generated much smaller clones than MPCs from wild-type or mdx dystrophic mice. Impaired proliferation of Sgca-null myogenic precursors was confirmed by single fiber analysis and this difference correlated with Sgca expression during MPC proliferation. In the absence of dystrophin and associated proteins, which are only expressed after differentiation, SGCA complexes with and stabilizes FGFR1. Deficiency of Sgca leads to an absence of FGFR1 expression at the membrane and impaired MPC proliferation in response to bFGF. The low proliferation rate of Sgca-null MPCs was rescued by transduction with Sgca-expressing lentiviral vectors. When transplanted into dystrophic muscle, Sgca-null MPCs exhibited reduced engraftment. The reduced proliferative ability of Sgca-null MPCs explains, at least in part, the severity of this muscular dystrophy and also why wild-type donor progenitor cells engraft efficiently and consequently ameliorate disease.

Alpha sarcoglycan is required for FGF-dependent myogenic progenitor cell proliferation in vitro and in vivo.

We recently showed that Magic-F1 (Met-activating genetically improved chimeric factor 1), a human recombinant protein derived from hepatocyte growth factor/scatter factor (HGF/SF) induces muscle cell hypertrophy but not progenitor cell proliferation, both in vitro and in vivo. Here, we examined the temporal and spatial expression pattern of Magic-F1 in comparison with Pax3 (paired box gene 3) transcription factor during embryogenesis. Ranging from 9.5 to 17.5 dpc (days post coitum) mouse embryos were analyzed by in situ hybridization using whole mounts during early stages of development (9.5-10.5-11.5 dpc) and cryostat sections for later stages (11.5-13.5-15.5-17.5 dpc). We found that Magic-F1 is expressed in developing organs and tissues of mesenchymal origin, where Pax3 signal appears to be downregulated respect to the wt embryos. These data suggest that Magic-F1 could be responsible of muscular hypertrophy, cooperating with Pax3 signal pathway in skeletal muscle precursor cells.

Flavio Ronzoni

Department of Pathology and Immunology,
Faculty of Medicine,
Department of Pathology and Immunology, Faculty of Medicine

University of Geneva

Harmonic Nanoparticles for Regenerative Research

Flavio Ronzoni

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University of Geneva

Harmonic Nanoparticles for Regenerative Research

Department of Pathology and Immunology,
Faculty of Medicine,
Department of Pathology and Immunology, Faculty of Medicine