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Regenerati vna medici na ce shiroka galuz medichnoyi nauki yaka spryamovana na regeneraciyu vidnovlennya abo zaminu poshkodzhenih abo hvorih klitin tkanin abo organiv dlya vidnovlennya yih zdorovoyi funkciyi v organizmi lyudini chi tvarini 1 2 SVF terapiya in yekciya stovburovih klitin v kolinnij suglobRegenerativna medicina osnovni napryamkiOsnovni napryami aktivaciya ta vikoristannya stovburovih klitin organoyidi tkaninna inzheneriya ta druk organiv genoterapiya ta redaguvannya genoma epigenomne pereprogramuvannya klitin molekulyarna ta nanomedicina nejroinzheneriya ta in 3 4 Regenerativna medicina formuyetsya na spivpraci medicini biomedicini ta biomedichnoyi inzheneriyi Zmist 1 Istoriya ta sogodennya 1 1 Rinok 2 Stovburovi klitini 2 1 Sercevo sudinna sistema 3 Tkaninna inzheneriya 3 1 Kistkova tkanina 3 2 Nervova tkanina 3 3 Sercevo sudinna sistema 4 Div takozh 5 Dodatkova literatura 5 1 Zagalna 5 1 1 Knigi 5 1 2 Zhurnali 5 1 3 Statti 5 2 Stovburovi klitini 5 2 1 Knigi 5 2 2 Zhurnali 5 2 3 Statti 5 3 Tkaninna inzheneriya 5 3 1 Knigi 5 3 2 Zhurnali 5 3 3 Statti 6 Posilannya 7 PrimitkiIstoriya ta sogodennya Redaguvati1943 Vilyam Kolf vinajshov pershu mashinu dlya nirkovogo dializu a Belding G Skribner poshiriv metodiku na pochatku 1960 h sho vstanovilo vihu dlya timchasovoyi zamini funkciyi organu 5 1954 Dzhozef Myurrej proviv pershu uspishnu transplantaciyu nirki 6 1981 pershe vidkrittya embrionalnih stovburovih klitin u mishej sho vidkrivalo mozhlivosti dlya regenerativnoyi medicini 7 1997 klonuvali vivcyu Dolli prodemonstruvavshi mozhlivosti klonuvannya ta regeneraciyi 8 1998 vidkrittya metodu otrimannya lyudskih embrionalnih stovburovih klitin i viroshuvati yih u laboratoriyi Ce vidkrittya lyaglo v osnovu suchasnoyi terapiyi stovburovimi klitinami 9 2002 persha uspishna transplantaciya autologichnogo sechovogo mihura skonstrujovanogo za dopomogoyu tkaninnoyi inzheneriyi 10 nbsp Lekciya Nobelevskogo laureata z fiziologiyi ta medicini Sin ya Yamanaka Nova era medicini z klitinami iPS poslannya majbutnim vchenim 2012 11 2006 Sin ya Yamanaka razom z komandoyu povidomili pro uspishnu transformaciyu doroslih klitin u plyuripotentni stovburovi klitini iPS klitini indukovani plyuripotentni stovburovi klitini sho zmenshilo etichni problemi vikoristannya embrionalnih stovburovih klitin dozvolivshi pereprogramovuvati zrili diferencijovani klitini nazad v stovburovi 12 2010 opisani organoyidi 13 miniatyurni modeli organiv chi tkanin zi stovburovih klitin sho dozvolyayut vivchati rozvitok lyudskih organiv modelyuvati hvorobi testuvati liki pidbirati personalizovane likuvannya vikoristovuvati v tkaninnij inzheneriyi ta yak dzherelo stovburovih klitin dlya terapiyi 14 2012 Robert Lanca Stiven D Shvarc ta in opisali klinichne vikoristannya embrionalnih stovburovih klitin lyudini dlya likuvannya pevnih tipiv slipoti 15 16 2014 persha demonstraciya mehanizmiv regeneraciyi organiv in situ u mishej 17 2016 persha uspishna transplantaciya klitin sitkivki otrimanih zi stovburovih klitin dlya likuvannya degeneraciyi zhovtoyi plyami sho daye nadiyu na vidnovlennya slipoti 18 2018 vcheni stvorili pershe 3D drukovane serce vikoristovuyuchi vlasni klitini paciyenta prodemonstruvavshi potencial 3D druku organiv 19 nbsp Genoterapiya mozhe zminiti genom ta epigenom klitin spriyayuchi regeneraciyi 20 21 22 napriklad zabezpechuyuchi bezperervnij lokalnij sintez faktoriv rostu ta morfogeniv 23 2020 provedena genoterapiya dlya omolodzhennya ta vidnovlennya nervovogo volokna sitkivki Starim misham vveli za dopomogoyu adenovirusnoyi genoterapiyi geni yaki sintezuyut faktori Yamanaki yaki epigenetichno omolodzhuyut gangliozni klitini sitkivki mishi sho spriyaye regeneraciyi aksoniv pislya poshkodzhennya 22 i usuvaye vtratu zoru na mishachij modeli glaukomi ta u litnih mishej 22 Take omolodzhennya klitin dozvolilo vidnoviti shtuchno poshkodzhenij zorovij nerv nervovi volokna virosli virosli znovu Vcheni dosyagli h2 zbilshennya kilkosti klitin sitkivki ta h5 priskorennya rostu zorovogo nerva 22 nbsp Transplantaciya ta integraciya korkovih organoyidiv lyudini v koru golovnogo mozku shuriv sho rozvivayetsya 24 2022 korkovi cerebralni organoyidi otrimani zi stovburovih klitin lyudini transplantovani v somatosensornu koru novonarodzhenih beztimusnih shuriv rozvivayut zrili tipi klitin yaki integruyutsya v sensorni ta motivacijni shemi 24 2023 organoyidi lyudskogo mozku uspishno integruyutsya iz zorovoyu sistemoyu doroslogo shura pislya transplantaciyi u veliki poshkodzheni porozhnini zorovoyi kori 25 She odne doslidzhennya pokazalo uspishne vidnovlennya funkciyi pislya integraciyi mozkovogo organoyida v dilyanku ishemichnogo insultu mishi 26 Takozh u 2023 roci bulo provedeno uspishne likuvannya stovburovimi klitinami infarktu miokarda u svinej 27 Takozh bulo predstavleno precizijnu robotizovanu platformu kultur klitin Cell X dlya efektivnogo virobnictva specifichnih dlya paciyenta iPSK i organoyidiv sitkivki demonstruyuchi potencial dlya klinichnogo konveyernogo virobnictva iPSK dlya autologichnoyi zamini klitin sitkivki 28 piznishe v serpni bulo predstavleno she odnu tehnologiyu avtomatizovanogo druku organoyidiv dlya testuvannya ta skriningu likiv 29 V serpni vijshlo doslidzhennya sho opisuye uspishnu transplantaciyu shuram sercevih organoyidiv skonstrujovanih z elektroprovidnimi kremniyevimi nanodrotami v miscya urazhennya infarktom miorkarda sho spriyalo znachnomu funkcionalnomu vidnovlennyu sercya 30 V ostanni roki regenerativna medicina predstavlyaye z sebe samostijnu disciplinu yaka burhlivo rozvivayetsya 31 U 2006 roci stav vihoditi pershij specializovanij naukovij zhurnal z regenerativnoyi medicini Regenerative Medicine Z yavlyayutsya chislenni instituti ta kompaniyi sho zajmayutsya rozrobkoyu metodik regenerativnoyi medicini ta nadannyam poslug takih yak likuvannya stovburovimi klitinami Biomedichni inzheneri biologi ta likari klinicisti pracyuyut razom z metoyu stvorennya tkanin ta organiv neobhidnih paciyentam dlya transplantaciyi ta z metoyu rozrobki metodiv instrumentiv ta tehnologij sho spriyayut regeneraciyi vlasnih klitin tkanin ta organiv u lyudej ta tvarin 32 Za ostanni dva desyatilittya tkaninna inzheneriya ta regenerativna medicina priveli do shvalenih terapij yaki vikoristovuyut autologichni vlasni abo alogenni donorski klitini dlya spriyannya vidnovlennyu tkanin Takih preparativ ye bagato na rinku napriklad Carticel dlya likuvannya defektiv hryasha Autologichna implantaciya hondrocitiv en laViv dlya zmorshok ta bagato inshih 2 Oglyad 2022 roku opublikovanij v Frontiers in Bioengineering and Biotechnology zaznachaye sho rozuminnya mozhlivostej vikoristannya klitinnoyi terapiyi stovburovimi klitinami pozaklitinnih vezikul ekzosom i strategij tkaninnoyi inzheneriyi dlya zastosuvan regenerativnoyi medicini z uporom na personalizovane likuvannya paciyenta postijno pokrashuyetsya Chislenni doklinichni ta klinichni viprobuvannya prodemonstruvali potuzhnij potencial likuvannya stovburovimi klitinami imunnih klitin ta ekzosom dlya modulyaciyi zapalnih imunnih reakcij i spriyannya neoangiogennij z utvorennyam novih sudin regeneraciyi v hvorih organah poshkodzhenih transplantatah i pri zapalnih zahvoryuvannyah 33 Oglyad 2023 roku opublikovanij v Pediatric Surgery International povidomlyaye sho sfera regenerativnoyi medicini sho ohoplyuye kilka disciplin vklyuchayuchi biologiyu stovburovih klitin i tkaninnu inzheneriyu prodovzhuye rozvivatisya zavdyaki nakopichennyu doslidzhen tehnologij manipulyuvannya klitinami gennoyi terapiyi ta novih materialiv Odnak dlya dosyagnennya kincevoyi meti stvorennya bioinzhenernih organiv dlya transplantaciyi she potribno virishiti nizku pitan Zokrema rozrobka skladnih tkanin i organiv vimagaye tonkogo poyednannya riznih vidpovidnih aspektiv ne tilki repopulyaciya kilkoh klitinnih fenotipiv ale j koriguvannya faktoriv seredovisha hazyayina takih yak angiogenez vaskulyarizaciya innervaciya ta imunomodulyaciya 34 Rinok Redaguvati Rozmir svitovogo rinku regenerativnoyi medicini ocinyuvavsya v 55 03 milyarda dolariv SShA v 2022 roci i ochikuyetsya sho z 2023 po 2030 rik vin bude zrostati na 15 7 u serednorichnomu tempi zrostannya 35 Stovburovi klitini Redaguvati nbsp Zahvoryuvannya ta stani pri yakih likuvannya stovburovimi klitinami ye perspektivnimOsnovna stattya Likuvannya stovburovimi klitinami Indukovani plyuripotentni embrionalni stovburovi klitini induced pluripotent stem cells iPSC abo iPS vdalosya otrimati z klitin riznih tkanin u pershu chergu fibroblastiv za dopomogoyu yih pereprogramuvannya u stovburovi klitini metodami genetichnoyi inzheneriyi zazvichaj za dopomogoyu kombinaciyi faktoriv Yamanaki 12 36 Oct4 Klf4 Sox2 ta c Myc nazvanih na chest Sin ya Yamanaka abo za dopomogoyu RNK 37 abo malih molekul 38 Taki indukovani plyuripotentni stovburovi klitini mozhlivo zgodom pereprogramuvati u bud yaki tipi klitin nervovi m yazovi pokrivni tosho 39 Sercevo sudinna sistema RedaguvatiDoslidzhennya 2023 roku na svinyah dijshlo do visnovku sho klitini poperedniki sercevih miocitiv KPM otrimani zi stovburovih klitin ye bagatoobicyayuchoyu mozhlivistyu dlya likuvannya infarktu miokarda u regenerativnij kardiologiyi 40 Funkcionalni doslidzhennya sercya pislya likuvannya stovburovimi klitinami viyavili znachne pokrashennya frakciyi vikidu livogo shlunochka cherez chotiri ta dvanadcyat tizhniv pislya transplantaciyi Mi takozh sposterigali znachne pokrashennya tovshini stinki shlunochka ta zmenshennya rozmiru infarktu pislya transplantaciyi klitin poperednikiv miocitiv p 0 05 Imunogistologichnij analiz viyaviv in vivo dozrivannya KPM u kardiomiociti Vazhlivo sho vsi svini vizhili bez utvorennya bud yakih puhlin abo anomalij Mi robimo visnovok sho plyuripotentni KPM otrimani zi stovburovih klitin ye bagatoobicyayuchoyu mozhlivistyu dlya likuvannya infarktu miokarda i sho voni mozhut pozitivno vplivati na regenerativnu kardiologiyu nbsp Tkaninna inzheneriya infografika Tkaninna inzheneriya Redaguvati source source source source source source source source source source source source source source track track Sho take tkaninna inzheneriya anglijskoyu Tkaninna inzheneriya ce stvorennya novih tkanin i organiv dlya terapevtichnoyi rekonstrukciyi poshkodzhenogo organu za dopomogoyu dostavki v potribnu oblast opornih struktur klitin molekulyarnih i mehanichnih signaliv dlya regeneraciyi Zvichajni implantati z inertnih materialiv mozhut usunuti tilki fizichni i mehanichni nedoliki poshkodzhenih tkanin Metoyu tkaninnoyi inzheneriyi ye vidnovlennya biologichnih metabolichnih funkcij tobto regeneraciyu tkanini a ne proste zamishennya yiyi sintetichnim materialom Nanotehnologiyi mozhut buti vikoristani yak chastina tkaninnoyi inzheneriyi shob dopomogti vidtvoriti abo vidnoviti abo zminiti formu poshkodzhenoyi tkanini za dopomogoyu vidpovidnih skeletiv na osnovi nanomaterialiv i faktoriv rostu U razi uspihu tkaninna inzheneriya mozhe zaminiti zvichajni metodi likuvannya taki yak transplantaciya organiv abo shtuchni implantati Tkaninna inzheneriya bazuyetsya na 4 komponentah Klitini Karkas dlya klitin Biomolekuli faktori rostu ta diferenciaciyi klitin nbsp Viroshuvannya in vitro embrionalnoyi slinnoyi zalozi mishi dlya transplantaciyiFizichnij ta mehanichnij vpliv dlya utvorennya potribnoyi strukturi U 2021 roci obsyag svitovogo rinku tkaninnoyi inzheneriyi stanoviv 12 76 milyarda dolariv SShA a do 2030 roku ochikuyetsya sho vin syagne priblizno 31 23 milyarda dolariv SShA zbilshuyuchis na 10 46 u serednomu protyagom prognozovanogo periodu z 2022 po 2030 rik 41 Kistkova tkanina Redaguvati Taki nanochastinki yak grafen vuglecevi nanotrubki disulfid molibdenu ta disulfid volframu vikoristovuyutsya yak zmicnyuyuchi agenti dlya vigotovlennya mehanichno micnih polimernih nanokompozitiv sho piddayutsya biologichnomu rozkladannyu dlya inzheneriyi kistkovoyi tkanini Dodavannya cih nanochastinok u polimernu matricyu v nizkih koncentraciyah 0 2 vagovih prizvodit do znachnogo pokrashennya mehanichnih vlastivostej polimernih nanokompozitiv pri stisku ta zgini Potencijno ci nanokompoziti mozhut buti vikoristani yak novij mehanichno micnij legkij kompozit yak kistkovi implantati Ukrayino amerikanskij startap A D A M rozrobiv metodiku druku kistok na bio 3D printeri 42 43 Nervova tkanina Redaguvati Osnovna stattya Inzheneriya nervovoyi tkanini nbsp Imunofluorescentne zobrazhennya kortikalnih organoyidiv viroshenih iz plyuripotentnih stovburovih klitinCya galuz tkaninnoyi inzheneriyi zoseredzhena na rozrobci funkcionalnih zaminnikiv nervovoyi tkanini dlya zamini abo vidnovlennya poshkodzhenoyi abo hvoroyi tkanini centralnoyi nervovoyi sistemi CNS abo periferichnoyi nervovoyi sistemi PNS Metoyu inzheneriyi nervovoyi tkanini ye vidnovlennya vtrachenoyi funkciyi nervovoyi sistemi za dopomogoyu materialiv klitin i faktoriv rostu nbsp Peptidni biorozkladni karkasi dlya inzheneriyi nervovoyi tkanini nbsp Cerebralni organoyidi lyudini z klitin lyudskogo mozku pid chas rozvitku Cya oblast doslidzhennya vklyuchaye v sebe principi materialoznavstva biologiyi ta inzheneriyi dlya proektuvannya ta rozrobki pristroyiv karkasiv i 3D kultur yaki spriyayut rostu vizhivannyu ta funkcionalnij integraciyi nejroniv i glialnih klitin Deyaki iz potencijnih zastosuvan nejrotkaninnoyi inzheneriyi vklyuchayut likuvannya travm spinnogo mozku cherepno mozkovih travm insultu hvorobi Parkinsona ta inshih staniv yaki prizvodyat do poshkodzhennya nervovoyi sistemi Napriklad doslidzhennya na mishah 2023 roku opublikovane v npj Regenerative Medicine sho doslidzhuvalo vikoristannya mozkovih organoyidiv dlya vidnovlennya funkcionalnoyi nervovoyi tkanini v misci urazhennya pislya ishemichnogo insultu pokazalo 44 Cherez kilka misyaciv mi viyavili sho transplantovani organoyidi dobre vizhili v urazhenomu infarktom yadri diferenciyuvalisya v cilovi nejroni vidnovlyuvali infarktnu tkaninu posilali aksoni do viddalenih mishenej mozku ta integruvalisya v nejronnij lancyug gospodarya tim samim usuvayuchi sensomotorni defekti povedinki mishej yaki perenesli insult todi yak transplantaciya disocijovanih okremih klitin z organoyidiv ne privela do vidnovlennya urazhenoyi infarktom tkanini Sercevo sudinna sistema Redaguvati V serpni 2023 roku vijshlo doslidzhennya sho opisuye uspishnu transplantaciyu shuram sercevih organoyidiv skonstrujovanih z elektroprovidnimi kremniyevimi nanodrotami v miscya urazhennya infarktom miorkarda sho spriyalo znachnomu funkcionalnomu vidnovlennyu sercya 30 She odne doslidzhennya opublikovane u veresni 2023 roku prodemonstruvalo stvorennya micnoyi sudinnoyi sistemi v mikrotkaninah sho skladayutsya z endotelialnih klitin fibroblastiv i peredserdnih abo shlunochkovih kardiomiocitiv yaki demonstruyut oznaki ekspresiyi geniv arhitekturnu ta elektrofiziologichnu shozhist z anatomichnimi tkaninami sercya otrimanimi in vivo 45 Hocha ce lishe odin z bagatoh prikladiv podibnih doslidzhen 46 47 i podibni zastosuvannya v osnovnomu 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