In vitro diferencijacija matičnih stanica u kardiomiocite

master's thesis

• Title (english): In vitro differentiation of stem cells into cardiomyocytes
• Author: Adam Zabini
• Mentor: Filip Sedlić (mentor)
• Committee member: Zdenko Kovač (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Filip Sedlić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pathophysiology); Zagreb
• Defense date and country: 2017-07-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pathophysiology

Abstract

Kardiomiociti – mišićne stanice srca, temeljne su stanice srčanog miokarda i odgovorne su za njegovu kontraktilnu sposobnost. Iako su dugo smatrani terminalno diferenciranim stanicama, danas je poznato da se i u odraslom srcu tijekom života neprestano obnavlja vrlo mali broj kardiomiocita; za sada nije razjašnjeno je li to posljedica proliferacije već postojećih kardiomiocita ili diferencijacije nekih drugih stanica. U svakom slučaju, in vivo regeneracija kardiomiocita nedovoljna je za obnovu tkiva i održavanje funkcije srca nakon opsežnih oštećenja, što je jedan od razloga što su kardiovaskularne bolesti glavni uzrok smrtnosti u većini gospodarski razvijenih zemalja. Zbog toga je u posljednje vrijeme veliki napor uložen u razvoj metoda koje bi omogućile in vitro diferencijaciju kardiomiocita iz matičnih i srodnih vrsta stanica, koje bi, između ostalog, otvorile vrata primjeni tehnika regenerativne biologije u ljudskoj medicini i znatno poboljšale terapijske opcije za veliki broj bolesnika. U ovom diplomskom radu bit će opisane neke od trenutno dostupnih metoda in vitro diferencijacije kardiomiocita (diferencijacija pomoću embrioidnih tjelešaca, diferencijacija u jednosloju i diferencijacija pomoću induktivne su-kulture), bit će navedene prednosti i nedostatci svake metode te će se raspraviti ograničenja koja bi trebala biti premoštena kako bi se postigao njihov puni potencijal. Osim toga, usporedit će se uspjeh diferencijacije iz različitih vrsta pluripotentnih stanica, kao što su embrionalne matične stanice i inducirane pluripotentne matične stanice. Konačno, cilj ovog rada je navesti dosadašnje dosege, nabrojati neke od budućih izazova, te naglasiti važnost daljnjih istraživačkih napora koji imaju mogućnost iz temelja promijeniti terapiju kardiovaskularnih i drugih bolesti.

Abstract (english)

Cardiomyocytes – heart muscle cells, are the principal cell type of cardiac muscle layer and are responsible for its contractility. Even though they were considered to be terminally differentiated cells for a very long time, it is now known that even the adult heart is capable of renewing a limited amount of cardiomyocytes; whether this is the result of the proliferation of existing cardiomyocytes or differentiation of some other cells is still incompletely understood. In either case, in vivo renewal of cardiomyocytes is thought to be insufficient to allow for tissue regeneration and to sustain adequate cardiac function following substantial damage, such as myocardial infarction. This is one of the primary reasons for cardiovascular diseases being the major cause of mortality in most industrialized countries. Consequently, great efforts have been made recently in developing methods of in vitro differentiation of cardiomyocytes from stem cells, which would, among other things, open doors to regenerative biology use in clinical medicine and significantly improve therapeutic outcome for many patients. This thesis paper shall focus on some of the currently available methods of in vitro
differentiation of cardiomyocytes, such as embryoid body formation, monolayer in vitro cultures and inductive co-cultures with visceral endoderm-like cells, as well as advantages and setbacks of each method, and limitations that still need to be surpassed before its full potential is reached. Additionally, efficiencies of differentiation from various types of pluripotent cells, such as embryonal stem cells and induced pluripotent stem cells shall be compared. Lastly, the aim of this thesis paper is to list the recent breakthroughs, mention future challenges and emphasize the importance of further research, seeing as it has the ability to fundamentally change the means of treatment of cardiovascular and other diseases.

• Keywords: kardiomiociti; diferencijacija; matične stanice; regeneracija; in vitro
• Keywords (english): cardiomyocytes; differentiation; stem cells; regeneration; in vitro
• Language: croatian
• URN:NBN: urn:nbn:hr:105:712176
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-10-27 12:39:58