CARDIAC STEM CELL TRANSPLANTATION IN THERAPY OF INFARCTED MYOCARDIUM

master's thesis

• Title: TRANSPLANTACIJA MATIČNIH STANICA U LIJEČENJU INFARKTA MIOKARDA
• Author: Ines Bosnić
• Mentor: Filip Sedlić (mentor)
• Committee member: Maja Sirotković-Skerlev (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Filip Sedlić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Chair of Pathophysiology); Zagreb
• Defense date and country: 2015-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pathophysiology

Abstract

Ljudsko srce ima ograničeni regenerativni kapacitet i zbog toga njegov funkcionalni oporavak predstavlja velik izazov. Unatoč dostignućima u farmakološkom i kiruškom liječenju ishemijskih bolesti miokarda, one su i dalje među glavnim uzrocima morbiditeta i mortraliteta u razvijenim zemljama. Nadomjestak oštećenih kardiomiocita nova je paradigma u liječenju, međutim ograničava je nedostatak ljudskih kardiomiocita koje bi se koristili u tu svrhu. Nedavna otkrića embrionalnih matičnih stanica, adultnih matičnih stanica, induciranih pluripotentnih matičnih stanica i unipotentnih satelitskih stanica, te matičnih stanica u samome srcu predstavljaju potencijalno riješenje problema. U ovome diplomskom radu baviti ću se vrstama stanica koje bi se mogle upotrijebiti u terapiji infarciranog miokarda, te prednostima i nedostatcima svake vrste. Spomenuti ću načine njihove primjene- intrakoronarno, intrakardijalno, stvaranje slojeva stanica ili tkiva za transplantaciju. Biti će opisane neke od studija na životinjama i do sada provedena, značajnija klinička istraživanja. Raspraviti ću potencijalne mehanizme kojima matične stanice mogu dovesti do poboljšanja srčane funkcije – diferencijacijom u nove kardiomiocite, imunomodulatornim učincima ili parakrinom signalizacijom. Neke od potencijalnih komplikacija će također biti spomenute, poput imunosnog odbacivanja, poticanja autoimunog odgovora i formacije tumora. Konačno, opisati ću predstojeće izazove, koji moraju biti prevladani prije šire kliničke upotrebe ove terapije.

Abstract (english)

Adult human heart has limited regenerative capacity, and therefore, functional restoration of the damaged heart presents a great challenge. Despite the progress achieved in the pharmacological and surgical treatment of ischemic myocardial diseases, they are still considered one of the major causes of morbidity and mortality in developed countires. Repopulation of the damaged heart with cardiomyocites represents a novel therapeutic paradigm, but is hampered by the lack of human cardiomyocites that would be used for this purpose. The recent derivation of human embryonic stem cell lines, adult stem cells, induced pluripotent stem cells, unipotent satellite cells, and cardiac resident stem cells may provide a solution for this problem. This thesis will focus on the types of stem cells that can be used for the treatment of infarcted myocardium and their potential sources. The means of stem cells application will be mentioned – intravenous, intracoronary, cell layers and engeneered tissues. Some of the experimental studies will be described, as well as some clinical trials. Potential mechanisms of stem cells contribution to heart regeneration – by differentiation to new cardiomyocites, immunomodulatory effects, or paracrine signalization – will be discussed. Some of the potential clinical complications of this procedure will also be discussed, such as graft rejection, inducton of autoimmune response and tumor formation. Finally, the hurdles and challenges toward fully harnessing the potential clinical applications of these unique cells will be described.

• Keywords: ishemijska bolest srca; matične stanice; regeneracija
• Keywords (english): ischemic cardiac disease; stem cells; regeneration
• Language: croatian
• URN:NBN: urn:nbn:hr:105:328882
• Study programme: Title: Medicina; Study programme type: sveučilišni; Study level: integrirani preddiplomski i diplomski; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2016-11-25 11:43:28