\u00a0a evolu\u0163iei modelelor tumorale ob\u0163inute prin bioimprimare 3D \u015fi modelarea \/ simularea computa\u0163ional\u0103 a rearanj\u0103rii celulelor dup\u0103 biotip\u0103rire.<\/span><\/p>\n[\/et_pb_blurb][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” width=”100%” max_width=”100%” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_blurb title=”Rezumatul proiectului:” content_max_width=”100%” _builder_version=”4.22.1″ _module_preset=”default” header_font=”|700||on|||||” header_font_size=”26px” body_font_size=”17px” body_line_height=”29px” global_colors_info=”{}”]<\/p>\n
\u00cen acest proiect, ne propunem s\u0103 realiz\u0103m constructe tisulare tridimensionale (3D) care mimeaz\u0103 micromediul tumoral. Acestea vor include un sistem multicelular, a c\u0103rei structur\u0103 va fi similar\u0103 tumorii, respectiv un \u00eenveli\u015f de celule \u00eencorporate \u00een matrice extracelular\u0103, care reprezint\u0103 vecin\u0103tatea tumorii.<\/p>\n
Pentru a le asambla, vom dezvolta metode de biotip\u0103rire tisular\u0103 3D, metod\u0103 ce apar\u0163ine ingineriei tisulare. Vom construi modele 3D ale unor tumori aflate \u00een mediul lor \u015fi le vom valida, caracteriz\u00e2ndu-le din punct de vedere morfologic, fenotipic, genotipic \u015fi func\u0163ional. Ne propunem s\u0103 utiliz\u0103m dou\u0103 surse celulare: linii celulare standard, precum \u015fi celule primare. Prima op\u0163iune e mai reproductibil\u0103, iar a doua are \u015fanse mai mari de a furniza modele tumorale mai realiste. Pentru fiecare tip celular, vom testa dou\u0103 metode de asamblare asistat\u0103 de calculator: biotip\u0103rirea unor hidrogeluri cu con\u0163inut celular aflat \u00een suspensie, \u015fi biotip\u0103rirea unor agregate celulare. Prima metod\u0103 asigur\u0103 o rezolu\u0163ie mai bun\u0103, iar a doua conduce la o densitate celular\u0103 mai mare.\u00a0<\/p>\n
Modelele tumorale ob\u0163inute vor fi validate pe \u015foareci immunosupresa\u021bi. \u00cen prealabil biotip\u0103ririi, celulele maligne \u015fi fibroblastele peritumorale vor fi transfectate stabil cu GFP, astfel \u00eenc\u00e2t tumorile vor putea fi vizualizate prin microscopie fluorescent\u0103 in vivo. De asemenea, constructele tisulare vor fi ierarhizate \u00een func\u0163ie de abilitatea lor de a mima comportamentul secretor al tumorilor in vivo.\u00a0<\/p>\n
\u00cen urma valid\u0103rii, rezultatele proiectului vor fi aplicabile \u00een studii ale terapiilor cancerului: modelele tumorale 3D vor fi utilizabile pentru testarea personalizat\u0103 a eficien\u0163ei unor agen\u0163i farmacologici, \u00een studii ale evolu\u0163iei tumorale, precum \u015fi \u00een studii care urm\u0103resc transferul rezultatelor in vitro \u0219i in vivo \u00een studii clinice, \u00een contextul larg al terapiilor antitumorale.\u00a0\u00a0<\/strong><\/p>\n[\/et_pb_blurb][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” width=”100%” max_width=”100%” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_blurb title=”Rezultate:” content_max_width=”100%” _builder_version=”4.22.1″ _module_preset=”default” header_font=”|700||on|||||” header_font_size=”26px” body_font_size=”17px” body_line_height=”29px” global_colors_info=”{}”]<\/p>\n
Am validat metodologia de bioprintare 3D a modelelor tumorale in vitro, folosind 3 tipuri celulare distincte, din mediul peri-tumoral (TAF \u0219i limfocite T) \u0219i celule tumorale; Au fost validate in vitro 2 modele tumorale distincte: modelul triplustratificat \u0219i modelul torsional; Am validat in vivo modelul tumoral bioprintat 3D triplustratificat pe \u0219oareci imunosupresa\u021bi CD1 Nu\/Nu; validarea dezvolt\u0103rii tumorale a fost f\u0103cut\u0103\u00a0<\/span>in vivo<\/em>\u00a0<\/span>cu ajutorul sistemului de imagistic\u0103 Hamamatsu Aequoria System (cuantificarea dezvolt\u0103rii tumorale), iar ulterior explant\u0103rii tumorale s-a efectuat validarea modelului in vitro, prin eviden\u021bierea distribu\u021biei celulare \u0219i expresia markerilor caracteristici; A fost validat modelul computa\u021bional de simulare a dezvolt\u0103rii tumorale.<\/p>\n\n- \n
\n- Procedeu experimental de realizare in vitro a unor sferiozi tumorali (Fig. 1)<\/li>\n
- Metod\u0103 de biotip\u0103rire a modelelor tumorale toroidale (Fig. 2A) \u015fi triplu-stratificate (Fig. 2B-D)<\/li>\n
- Procedeu de cultivare in vitro a modelelor tisulare biotip\u0103rite (Fig. 4)<\/li>\n
- Procedeu de cultivare in vivo a modelelor tisulare prin implantare subcutanat\u0103 \u00een \u015foareci imunosupresa\u0163i (CD1 Nu\/Nu) (Fig. 5)<\/li>\n
- Programe G-code pentru bioimprimarea modelelor tisulare reprezentate \u00een Fig. 2<\/li>\n
- Modele computa\u0163ionale de rezolu\u0163ie celular\u0103 a structurilor tisulare \u015fi programe de simulare a evolu\u0163iei acestora (Fig.3)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n
[\/et_pb_blurb][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_3,1_3,1_3″ _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”1_3″ _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”https:\/\/oncogen.ro\/wp-content\/uploads\/2023\/09\/delimit1.jpg” title_text=”delimit1″ _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_image][et_pb_text _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n
Fig. 1. Sferoizi tumorali de cancer de colon HT-29 vizualiza\u0163i prin stereomicroscopie (reper = 200 micrometri)<\/span><\/p>\n[\/et_pb_text][et_pb_image src=”https:\/\/oncogen.ro\/wp-content\/uploads\/2023\/09\/delimit4.jpg” title_text=”delimit4″ _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_image][et_pb_text _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n
Fig. 4. Colora\u021bie HE a modelelor tumorale bioprintate dup\u0103 6 zile de cultivare in vitro<\/span><\/p>\n[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”https:\/\/oncogen.ro\/wp-content\/uploads\/2023\/09\/delimit2.jpg” title_text=”delimit2″ _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_image][et_pb_text _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n
Fig. 2. Modele digitale ale structurilor tisulare dezvoltate: model toroidal (A) si model triplu-stratificat (B-D).<\/span><\/p>\n[\/et_pb_text][et_pb_image src=”https:\/\/oncogen.ro\/wp-content\/uploads\/2023\/09\/delimit5.jpg” title_text=”delimit5″ _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_image][et_pb_text _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n
Fig. 5. Model tumoral triplu-stratificat cultivat in vivo<\/span><\/p>\n[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”https:\/\/oncogen.ro\/wp-content\/uploads\/2023\/09\/delimit3.jpg” title_text=”delimit3″ _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_image][et_pb_text _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n
Fig. 3. Modele computa\u0163ionale ale structurilor tisulare realizate la scara 1:1, vizulalizate cu (A, C) \u015fi f\u0103r\u0103 hidrogelul dispersant (B, D).<\/span><\/p>\n[\/et_pb_text][et_pb_image src=”https:\/\/oncogen.ro\/wp-content\/uploads\/2023\/09\/delimit6.jpg” title_text=”delimit6″ _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_image][et_pb_text _builder_version=”4.22.1″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n
Fig. 6. Experiment de optimizare a procesului de tip\u0103rire realizat cu dou\u0103 tipuri de hidrogel<\/span><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.22.1″ _module_preset=”default” width=”100%” max_width=”100%” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_blurb title=”Participare la manifest\u0103ri \u015ftiin\u0163ifice:” content_max_width=”100%” _builder_version=”4.22.1″ _module_preset=”default” header_font=”|700||on|||||” header_font_size=”26px” body_font_size=”17px” body_line_height=”29px” global_colors_info=”{}”]<\/p>\n
\n- Neagu A, Bojin F, Bejenariu MI, Neagu M, Cristea A, Popescu R, P\u0103unescu V. 3D bioprinting techniques for building model tissues\u201d \u2013 prelegere oral\u0103, a 29-a Conferin\u0163\u0103 Na\u0163ional\u0103 a Societ\u0103\u0163ii Rom\u00e2ne de Fiziologie, 25 \u2013 27 mai 2017, Timi\u015foara.<\/li>\n
- Bojin F, Neagu A, Bejenariu MI, Cean A, Popescu R, Neagu M, Cristea A, P\u0103unescu V. \u201e3D bioprinting techniques for building model tissues that mimic the tumor microenvironment\u201d \u2013 prelegere oral\u0103, BIOFABRICATION 2017 International Conference on Biofabrication, 15-18 octombrie 2017, Beijing, China. mai importante realiz\u0103ri din prima etap\u0103 de implementare a proiectului.<\/li>\n
- Bojin F, Bejenariu MI, Robu A, Cean A, Popescu R, Neagu M, Gavriliuc O, Neagu A, P\u0103unescu V. \u201eBioprinted models of the tumor microenvironment: in vivo evaluation and computer simulations\u201d \u2013 prelegere oral\u0103, BIOFABRICATION 2018 International Conference on Biofabrication, 28-31 octombrie 2018, W\u00fcrzburg, Germania.<\/li>\n
- Neagu A, Brakke K, Robu A, Bejenariu MI, Koudan E, Bulanova E, Parfenov V, Hesuani Y, Kharin A, Timoshenko V, Mironov V, \u201eSacrificial multicellular spheroids (sacrospheres) for the biofabrication of tubular tissue constructs\u201d, poster, BIOFABRICATION 2017 International Conference on Biofabrication, 15-18 octombrie 2017, Beijing, China.<\/li>\n<\/ol>\n
[\/et_pb_blurb][et_pb_blurb title=”Articole in extenso:” content_max_width=”100%” _builder_version=”4.22.1″ _module_preset=”default” header_font=”|700||on|||||” header_font_size=”26px” body_font_size=”17px” body_line_height=”29px” global_colors_info=”{}”]<\/p>\n
\n- Neagu A. (2017) Role of computer simulation to predict the outcome of 3D bioprinting. Journal of 3D Printing in Medicine 1(2):103-121.<\/li>\n
- Robu A, Robu N, Neagu A. (2018) New software tools for hydrogel-based bioprinting. Proceedings of SACI 2018, IEEE 12th International Symposium on Applied Computational Intelligence and Informatics, May 17-19, 2018, Timisoara, Romania. \u2013 articol in extenso publicat \u00een volumul de Proceedings al conferin\u0163ei (DOI: 10.1109\/SACI.2018.8440971).<\/li>\n<\/ol>\n
[\/et_pb_blurb][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"
Proiectul DeLIMIThttp:\/\/www.3dbioprinting-oncogen.com\/18 luni100PED\/03.01.2017Spitalul Clinic Jude\u021bean de Urgen\u021b\u0103 \u201ePius Br\u00eenzeu\u201d Timi\u0219oara \u2013\u00a0OncoGenUniversitatea de Medicin\u0103 \u0219i Farmacie \u201eVictor Babe\u0219\u201d Timi\u0219oaraPDFGenerarea sferoizilor tumorali de cancer mamar \u0219i de colon, realizarea sferoizilor multicelulari prin bioimprimare 3D \u0219i caracterizarea\u00a0in vitro\u00a0a modelelor tumorale.\u00a0Validarea\u00a0in vivo\u00a0a modelului tumoral optim realizat prin bioimprimarea 3D, care a cuprins evaluarea\u00a0in vivo\u00a0a evolu\u0163iei modelelor tumorale ob\u0163inute prin […]<\/p>\n","protected":false},"author":2,"featured_media":100879,"comment_status":"open","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","inline_featured_image":false,"footnotes":""},"project_category":[],"project_tag":[],"class_list":["post-100562","project","type-project","status-publish","has-post-thumbnail","hentry"],"_links":{"self":[{"href":"http:\/\/oncogen.ro\/ro\/wp-json\/wp\/v2\/project\/100562","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/oncogen.ro\/ro\/wp-json\/wp\/v2\/project"}],"about":[{"href":"http:\/\/oncogen.ro\/ro\/wp-json\/wp\/v2\/types\/project"}],"author":[{"embeddable":true,"href":"http:\/\/oncogen.ro\/ro\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"http:\/\/oncogen.ro\/ro\/wp-json\/wp\/v2\/comments?post=100562"}],"version-history":[{"count":7,"href":"http:\/\/oncogen.ro\/ro\/wp-json\/wp\/v2\/project\/100562\/revisions"}],"predecessor-version":[{"id":101001,"href":"http:\/\/oncogen.ro\/ro\/wp-json\/wp\/v2\/project\/100562\/revisions\/101001"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/oncogen.ro\/ro\/wp-json\/wp\/v2\/media\/100879"}],"wp:attachment":[{"href":"http:\/\/oncogen.ro\/ro\/wp-json\/wp\/v2\/media?parent=100562"}],"wp:term":[{"taxonomy":"project_category","embeddable":true,"href":"http:\/\/oncogen.ro\/ro\/wp-json\/wp\/v2\/project_category?post=100562"},{"taxonomy":"project_tag","embeddable":true,"href":"http:\/\/oncogen.ro\/ro\/wp-json\/wp\/v2\/project_tag?post=100562"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}