{"id":980,"date":"2015-01-12T10:30:13","date_gmt":"2015-01-12T09:30:13","guid":{"rendered":"https:\/\/futurehealthbiobank.com\/rs\/?p=980"},"modified":"2016-08-10T10:33:26","modified_gmt":"2016-08-10T08:33:26","slug":"mezenhimalne-maticne-celije-iz-tkiva-pupcane-vrpce-u-lecenju-bolesti-graft-versus-host-disease-gvhd","status":"publish","type":"post","link":"https:\/\/futurehealthbiobank.com\/rs\/blog\/mezenhimalne-maticne-celije-iz-tkiva-pupcane-vrpce-u-lecenju-bolesti-graft-versus-host-disease-gvhd\/","title":{"rendered":"MEZENHIMALNE MATI\u010cNE \u0106ELIJE IZ TKIVA PUP\u010cANE VRPCE U LE\u010cENJU BOLESTI (Graft versus Host Disease – GvHD)"},"content":{"rendered":"

Bolest\u00a0Graft versus Host Disease<\/em>\u00a0– GvHD \u00a0je uobi\u010dajena i ozbiljna komplikacija koja prati postupak transplantacije mati\u010dnih \u0107elija od nesrodnih donora. Bolest\u00a0Graft versus Host Disease<\/em>\u00a0– GvHD\u00a0 mo\u017ee se pojaviti u akutnom i hroni\u010dnom obliku, u zavisnosti od klini\u010dkog toka i vremena postavljanja dijagnoze. Radi se o stanju opasnom po \u017eivot, koje u velikoj meri doprinosi ranom mortalitetu nakon transplantacije mati\u010dnih \u0107elija. Osobe koje pre\u017eive, mogu patiti od o\u0161te\u0107enja organa i imati znatno o\u0161te\u0107en kvalitet \u017eivota.<\/p>\n

<\/p>\n

Prva linija prevencije i le\u010denja GcHD stanja, su steroidi. Kada GvHD ne daje rezultate na primenu steroida ili se situacija ne re\u0161ava steroidima, ka\u017eemo da postoji \u201esteroidna-otpornost\u201c. U ovoj situaciji postoji veliki broj sekundarnih terapija, ali se ni jedna od njih ne smatra superiornom ili najefikasnijom.<\/p>\n

Usled svojih jedinstvenih karakteristika, mezenhimalne mati\u010dne \u0107elije (MSC) imaju veliki potencijal kao opcija le\u010denja steroidne-otpornosti GvHD. Jedan od atributa mezenhimalnih mati\u010dnih \u0107elija je da donor i pacijent ne moraju da se poklapaju, tako se mezenhimalne \u0107elije mogu veoma lako nabaviti u banci donora. Jo\u0161 jedan veoma va\u017ean atribut je, da brojne studije pokazuju te\u017enju mezenhimalnih \u0107elija da potisnu auto-imune reakcije \u010dime bi potencijalno mogli da potisnu konflikt izme\u0111u kalema i imunog sistema doma\u0107ina. \u0160tavi\u0161e, MSC mogu biti transpatovane intravenozno, \u0161to je veoma pogodno za pacijente.<\/p>\n

U ovom \u010danku izve\u0161tavamo o seriji pacijenata u \u010dijem su le\u010denju od bolesti\u00a0Graft versus Host Disease<\/em>\u00a0– GvHD\u00a0 kori\u0161\u0107ene mezenhimalne mati\u010dne \u0107elijama iz Wharton-ovog gela (Wharton\u2019s jelly) tkiva pup\u010dane vrpce (WJ-MSC), u Poljskoj. Wharton-gel je veoma bogat izvor mezenhimalnih mati\u010dnih \u0107elija, sa nekoliko prednosti: uzimanje tkiva pup\u010dane vrpce je neinvanzivno i MSC se veoma jednostavno izoluju, MSC iz tkiva pup\u010dane vrpce imaju dobre sposobnosti proliferacije i diferencijacije.<\/p>\n

U periodu 2011-2013. godine, deset pacijenata sa dijagnozom bolesti\u00a0Graft versus Host Disease<\/em>\u00a0– GvHD\u00a0 podvrgnuto je terapiji u \u010detiri razli\u010dite klinike u Poljskoj. Tretman le\u010denja, izveden je pomo\u0107u mezenhimanih mati\u010dnih \u0107elija koje su obezbe\u0111ene iz Wharton-ovog gela, kao spasonosna terapija za ovu bolest. Svakoj primeni je prethodilo odobrenje komisije za bioeti\u010dka pitanja. Starost pacijenata se kretala izme\u0111u 3 i 20 godina. Me\u0111u le\u010denim pacijentima, troje je imalo ektenzivni hroni\u010dni oblik GvHD i sedmoro njih je patilo od akutnog oblika GvHD, uklju\u010duju\u0107i \u0161est pacijenata sa stepenom IV i stepenom III.<\/p>\n

Pacijenti su prvobitno bili podvrgnuti transplantaciji mati\u010dnim \u0107elijama usled postojanja osnovne bolesti: akutne limfoblastne leukemije (ALL), akutne mijeloidne leukemije (AML), mijelodisplazni sindroma (MDS) transformiranog u AML, MDS, ozbiljne aplasti\u010dne anemije, i ne-Hod\u017ekin limfoma. Svi pacijenti su neuspe\u0161no reagovali na prvu liniju terapije GvHD koja je podrazumevala primenu steroida, i imali su nezadovoljavaju\u0107u reakciju na sekundarnu-liniju terapije, uklju\u010duju\u0107i:\u00a0ciklosporin A, mikofenolat mofetil, takrolimus, anti-timocitni globulin, etanercept, intravenozni imunoglobulin, ekstrakorporalna fotofereza i monoklonalna antitela<\/em>.<\/p>\n

Pacijenti sa GvHD, primili su 1-3 intravenozne infuzije WJ-MSC od nekoliko nezavisnih donora u toku 1-2 nedeljnog intervala. Primali su srednju ukupnu dozu od 1.5 miliona \u0107elija po kilogramu telesne mase. Wharton-gel (Wharton\u2019s jelly) je bio izolovan mehani\u010dkom disekcijom prikupljenog tkiva pup\u010dane vrpce, zatim su plasti\u010dne-adherentne \u0107elije (MSC) izolovane bez enzimatske terapije, kultivirane, i izvr\u0161ena je krioprezervacija u te\u010dnom azotu. Laboratorijska obrada se odvijala u GMP ISO 5 okru\u017eenju. Referentni uzorci mezinhemalnih mati\u010dnih \u0107elija, kori\u0161\u0107eni su za proveru broja \u0107elija, vitalnosti, i imunofenotipa. Mezenhimalne \u0107elije su administrirane odmah nakon odmrzavanja.<\/p>\n

Usled mogu\u0107ih negativnih efekata, pacijenti su pra\u0107eni tokom kompletnog perioda primene terapije i nakon toga. Prose\u010dno vreme opservacije pacijenata, iznosio je oko 9.5 meseci. Nije bilo opisanih \u0161tetnih efekata tokom ili nakon primene WJ-MSC, osim prolazne tahikardije koja je smirena bez dodatnih intervencija.<\/p>\n

\u0160est od ukupno deset pacijenata sa GvHD, pozitivno je reagovalo na primenu terapije, usled \u010dega je bilo mogu\u0107e smanjenje doze imunosupresivnog tretmana, uklju\u010duju\u0107i jednog pacijenta sa hroni\u010dnim oblikom GvHD koji je pokazao pobolj\u0161anje tri meseca nakon primene MSC. Dva pacijenta su pokazala potpunu reakciju, i bili oslobo\u0111eni GvHD simptoma. Prvi pacijent koji je pokazao potpuno ozdravljenje, bila je sedmogodi\u0161nja devoj\u010dica da IV stepenom akutne intestinalne GvHD, kojoj je transplantacija izvr\u0161ena zbog akutne limfoblastne leukemije u drugoj remisiji. Drugi pacijent, bio je trogodi\u0161nji de\u010dak sa IV stepenom ko\u017ene i intestinalne akutne GvHD, koji je bolovao od mijelodisplazni sindroma (MDS) transformisanog u AML. Oba pacijenta su primila terapiju mezenhimalnim mati\u010dnim \u0107elijama odmah nakon uspostavljanja dijagnoze bolesti\u00a0Graft versus Host Disease<\/em>\u00a0– GvHD. Od \u010detvoro preostalih pacijenata koji su u potpunosti reagovali na terapiju, dvoje je patilo od ograni\u010dene hroni\u010dne GvHD (pre toga je bila ekstenzivna), i jedan od njih, umro je tri meseca nakon terapije, usled krvarenja u centralnom nervnom sistemu i iznenadnog sr\u010danog zastoja. Poslednji pacijent iz ove grupe, je trenutno ocenjen, me\u0111utim, mesec dana nakon primene MSC tretmana, pacijent sa najvi\u0161im stepenom ozbiljnosti GvHD smanjen je sa IV na I stepen ozbiljnosti.<\/p>\n

Od \u010detiri pacijenta koja nisu adekvatno reagovala na primenu terapiju, jedan je u stabilnom stanju sa hroni\u010dnom ekstenzivnom GvHD, dok su ostala tri pacijenta umrla: dvoje, usled GvHD progresije i sepse, i jedan (sa stepen IV akutne GvHD koja je uklju\u010divala ko\u017eu, intestinalnu oblast i jetru) usled posledica hepati\u010dne home. Tokom perioda pra\u0107enja, nije zabele\u017eena pojava recidiva ili pojava novih oblika maligniteta.<\/p>\n

Primena WJ-MSC od nezavisnih donora, predstavlja bezbednu proceduru koja donosi zna\u010dajne klini\u010dke efekte, \u010dak i kada se primenjuje kao vrsta \u201espasonosne\u201c terapije. Kod vi\u0161e od polovine ovih pacijenata, WJ-MSC terapija ubla\u017eila je simptome bolesti kalem protiv doma\u0107ina, i dozvolila smanjenje imunosuprestivne terapije. Kod jedne petine pacijenata, WJ-MSC terapija dovela je do nestanka simptoma bolesti. Smatra se, da su ishodi bili pobolj\u0161ani kada je vreme izme\u0111u uspostavljanja dijagnoze i primene MSC terapije, bilo kra\u0107e.<\/p>\n

Danas, MSC se zvani\u010dno smatra sekundarnom linijom terapije kod akutnih oblika GvHD. Me\u0111utim, neophodna su dalja istra\u017eivanja u cilju uspostavljanja pode\u0161avanja vremena infuzije, optimalne doze \u0107elija, kao i broja infekcija i intervala izme\u0111u njih. Ovi slu\u010dajevi su objavljeni u rezimeu knjige na \u010detrdesetom Godi\u0161njem Sastanku Evropske Grupe za Transplantaciju Krvi i Ko\u0161tane Sr\u017ei.<\/p>\n","protected":false},"excerpt":{"rendered":"

Bolest\u00a0Graft versus Host Disease\u00a0– GvHD \u00a0je uobi\u010dajena i ozbiljna komplikacija koja prati postupak transplantacije mati\u010dnih \u0107elija od nesrodnih donora. Bolest\u00a0Graft versus Host Disease\u00a0– GvHD\u00a0 mo\u017ee se pojaviti u akutnom i hroni\u010dnom obliku, u zavisnosti od klini\u010dkog toka i vremena postavljanja dijagnoze. Radi se o stanju opasnom po \u017eivot, koje u velikoj meri doprinosi ranom mortalitetu […]<\/p>\n","protected":false},"author":25,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-980","post","type-post","status-publish","format-standard","hentry","category-uncategorised"],"acf":[],"yoast_head":"\nMEZENHIMALNE MATI\u010cNE \u0106ELIJE IZ TKIVA PUP\u010cANE VRPCE U LE\u010cENJU BOLESTI (Graft versus Host Disease - GvHD) - Future Health Biobank Serbia<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/futurehealthbiobank.com\/rs\/blog\/mezenhimalne-maticne-celije-iz-tkiva-pupcane-vrpce-u-lecenju-bolesti-graft-versus-host-disease-gvhd\/\" \/>\n<meta property=\"og:locale\" content=\"sr_RS\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"MEZENHIMALNE MATI\u010cNE \u0106ELIJE IZ TKIVA PUP\u010cANE VRPCE U LE\u010cENJU BOLESTI (Graft versus Host Disease - GvHD)\" \/>\n<meta property=\"og:description\" content=\"Bolest\u00a0Graft versus Host Disease\u00a0– GvHD \u00a0je uobi\u010dajena i ozbiljna komplikacija koja prati postupak transplantacije mati\u010dnih \u0107elija od nesrodnih donora. 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Bolest\u00a0Graft versus Host Disease\u00a0– GvHD\u00a0 mo\u017ee se pojaviti u akutnom i hroni\u010dnom obliku, u zavisnosti od klini\u010dkog toka i vremena postavljanja dijagnoze. 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