Regenerativni učinak matičnih stanica oralne sluznice na hipoksijski oštećene neurone in vitro

doctoral thesis

• Title (english): Regenerative effect of oral mucosa stem cells on hypoxia damaged neurons in vitro
• Author: Paula Stančin
• Mentor: Dinko Mitrečić (mentor)
• Committee member: Nataša Jovanov Milošević (predsjednik povjerenstva)
• Committee member: Martina Rinčić (član povjerenstva)
• Committee member: Srećko Gajović (član povjerenstva)
• Committee member: Mirna Golemović (član povjerenstva)
• Committee member: Goran Šimić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Croatian Institiute for Brain Research); Zagreb
• Defense date and country: 2025-03-17, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

Regenerativna medicina je moderna disciplina koja jedan dio svojih uspjeha temelji na terapijskom učinku matičnih stanica i molekula koje one izlučuju. Ipak, mnoge vrste matičnih stanica se teško dobivaju ili je njihova primjena povezana s etičkim nedoumicama, pa je pronalaženje lako dostupnih izvora stanica važno za daljnji napredak. Ovo istraživanje je opisalo novu populaciju matičnih stanica, dobivenu biopsijom oralne sluznice, nazvanih ljudske matične stanice oralne sluznice (hOMSC). Nakon što smo usporedbom različitih protokola uspostavili postupak kojim dobivamo dovoljnu količinu homogenih stanica koje su
diferencijacijom oblikovale strukture tipične za nezrele ektodermalne stanice, testiranjem različitih biljega smo ovu populaciju definirali kao značajno pozitivnu na nestin i CD166, uz mjerljivu prisutnost OCT4, SOX2, CD90, CD40 i SNAIL2. Testiranje njihove otpornosti na anoksiju je otkrilo kako oralne matične stanice bolje preživljavaju u odnosu na iPSC. Također, hOMSC izlučuju regenerativne molekule BDNF, VEGF i NGF što je ovisilo o duljini kontakta s neuronima. Isto tako je pokazano kako oralne matične stanice povećavaju preživljenje ljudskih neurona oštećenih manjkom kisika. Sve navedeno ukazuje kako je ovo istraživanje uspostavilo protokol dobivanje stanične populacije iz razmjerno lako dostupnog izvora koja ima značajan potencijal u liječenju ishemijski oštećenog živčanog tkiva.

Abstract (english)

Regenerative medicine is a contemporary discipline that relies part of its success on the therapeutic effects of stem cells and the molecules they secrete. However, many types of stem cells are difficult to obtain or are associated with ethical concerns, making the identification of easily accessible cell sources crucial for further advancement. This study describes a novel population of stem cells, obtained through oral mucosa biopsy, referred to as human oral mucosa stem cells (hOMSC). By comparing different protocols, we established a method to obtain enough of homogeneous cells that differentiate into structures typical of immature ectodermal cells. Through marker analysis, this population was characterized as significantly positive for nestin and CD166 with a measurable expression of OCT4, SOX2, CD90, CD40, and SNAIL2. Testing their resistance to anoxia revealed that oral stem cells exhibit substantial resilience under extreme conditions compared to iPSC. Additionally, hOMSC secretes essential regenerative molecules: BDNF, VEGF, and NGF. The duration of contact with neurons modulates the secretion levels of these molecules. It was also demonstrated that oral stem cells enhance the survival of human neurons subjected to hypoxic damage. These findings indicate that this study has established a protocol for deriving a cell population from an easily accessible source with significant potential for treating ischemic neural tissue damage.

• Keywords: Sluznica usta; Regenerativne molekule; Inducirane pluripotentne matične stanice; Regenerativna medicina; Neuroni; Biopsija; Hipoksija
• Keywords (english): Oral mucosa; Regenerative molecules; Induced pluripotent stem cells; Regenerative medicine; Neurons; Biopsy; Hypoxia
• Language: croatian
• URN:NBN: urn:nbn:hr:105:577333
• Study programme: Title: Neuroscience; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 106 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-03-27 08:35:18