Vpliv polifenolov na hondrogeno diferenciacijo mezenhimskih matičnih celic pri bolnikih z osteoartrozo

Sirše, Mateja

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Title:	Vpliv polifenolov na hondrogeno diferenciacijo mezenhimskih matičnih celic pri bolnikih z osteoartrozo
Authors:	ID Sirše, Mateja (Author) ID Fokter, Samo K. (Mentor) More about this mentor... ID Zupan, Janja (Comentor)
Files:	DOK_Sirse_Mateja_2023.pdf (1,22 MB) MD5: 36B607C6FAF4134B8CA66EFF7A8A16F8
Language:	Slovenian
Work type:	Doctoral dissertation
Typology:	2.08 - Doctoral Dissertation
Organization:	MF - Faculty of Medicine
Abstract:	Osteoartroza je najpogostejša bolezen sklepov pri starejših ljudeh, za katero so značilni napredovalo uničenje sklepnega hrustanca, spremembe v subhondralni kostnini s formacijo ektopične kostnine in cist, hipertrofija sklepne kapsule in obsklepnih tkiv ter vnetje sinovijske ovojnice. Kljub številnim raziskavam ostaja etiopatogeneza bolezni neznana, saj gre za kompleksen konglomerat genetskih, mehanskih in vnetnih dejavnikov. Na molekularni ravni gre za neravnovesje med anabolnimi in katabolnimi procesi, ki ustvarjajo začarani krog vnetja nizke stopnje, v katerega so vpleteni interlevkini 1β in 6, tumor nekrotizirajoči faktor alfa, encimi razgradnje hrustančnega matriksa ter kompleksni učinki staranja, celične senescence, apoptoze in avtofagije, medsebojno povezani z več signalnimi potmi. Posledica katabolnih procesov je napredujoča izguba strukture in funkcije sklepnega hrustanca s prestrukturiranjem subhondralne kostnine in obsklepnih tkiv, kar vodi v degeneracijo in uničenje sklepa. Vse več znanstvenih raziskav je usmerjenih v iskanje novih (naravnih) učinkovin, ki bi podobno kot biološka zdravila vplivale na različne patofiziološke mehanizme in zmanjšale aktivnost vnetnih procesov. Med drugim se je za izjemno učinkovito izkazalo protivnetno delovanje številnih polifenolnih spojin. V disertaciji podajamo potek in rezultate raziskave, v kateri smo ugotavljali vpliv štirih izbranih polifenolnih spojin na hondrogeno diferenciacijo mezenhimskih matičnih/stromalnih celic, izoliranih iz trabekularne kosti človeka v pogojih in vitro. Pri tem smo preiskovali dve polifenolni spojini (resveratrol in kvercetin) in dva polifenolna izvlečka (Pycnogenol® in Belinal®), s katerimi smo tretirali mezenhimske matične/stromalne celice, izolirane iz človeške trabekularne kosti kolka in golenice v vnetnih in nevnetnih pogojih. Pri mezenhimskih matičnih/stromalnih celicah zdravih darovalcev ob tretiranju s preiskovanimi spojinami ni bilo pomembnih razlik v hondrogenezi. Pri mezenhimskih matičnih/stromalnih celicah bolnikov z osteoartrozo pa je Belinal® v nevnetnih pogojih pomembno izboljšal hondrogenezo v primerjavi z resveratrolom in kontrolo. V vnetnih pogojih je od vseh spojin samo Belinal® izboljšal sposobnost hondrogeneze mezenhimskih matičnih/stromalnih celic pridobljenih iz bolnikov z osteoartrozo. Rezultati te doktorske naloge tako dokazujejo potencialno vlogo polifenolnih spojin, kot je Belinal®, pri izboljšanju lastnosti humanih mezenhimskih matičnih/stromalnih celic v pogojih in vitro in predstavljajo osnovo za nadaljnje študije za razvoj učinkovitih celičnih terapij za zdravljenje osteoartroze.
Keywords:	osteoartroza, mezenhimske matične/stromalne celice, hondrogena diferenciacija, provnetni citokini, rastlinski polifenoli, regeneracija hrustanca
Place of publishing:	Maribor
Year of publishing:	2022
PID:	20.500.12556/DKUM-81576
COBISS.SI-ID:	143083523
Publication date in DKUM:	24.02.2023
Views:	911
Downloads:	81
Metadata:
Categories:	MF
:	SIRŠE, Mateja, 2022, Vpliv polifenolov na hondrogeno diferenciacijo mezenhimskih matičnih celic pri bolnikih z osteoartrozo [online]. Doctoral dissertation. Maribor. [Accessed 23 March 2025]. Retrieved from: https://dk.um.si/IzpisGradiva.php?lang=eng&id=81576 Copy citation

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Licences

License:	CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

Link:	http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:	The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:	19.04.2022

Secondary language

Language:	English
Title:	EFFECT OF POLYPHENOLS ON CHONDROGENIC DIFFERENTIATION OF MESENCHYMAL STEM/ STROMAL CELLS IN PATIENTS WITH OSTEOARTHRITIS
Abstract:	Osteoarthritis is the most common joint disorder in elderly people characterized by progressive destruction of the joint bone marrow, changes in the subhondral bone with the formation of ectopic bone, hypertrophy of joint capsule and synovial inflammation. Despite numerous studies, etiopathogenesis of the disease remains unknown, as it is a complex conglomerate of genetic, mechanical and inflammatory factors. At the molecular level, there is an imbalance between anabolic in catabolic processes, which generate a vicious circle involving inflammatory interleukin 1β and 6, tumor necrosis factor alpha, matrix metaloproteinases and complex effects of aging, cell senescence, apoptosis and autophagy that are connected through several signal channels. The consequence of catabolic processes is a progressive loss of the structure and function of the joint with the restructuring of the subhondral bone and the periarticular tissues leading to degeneration and destruction of the joint. Recently, growing evidence has emerged on the exhaustion of regenerative mechanisms in osteoarthritis patients such as decreased ability of the endogenous mesenchymal stem/ stromal cells to regenerate cartilage and the higher rate of the senescence of these cells. An increasing number of scientific studies focus on the search for new (natural) substances, which could, similarly to biological medicines, reduce the activity of inflammatory processes. Among others, the anti-inflammatory action of many polyphenolic compounds has been proven scientifically. In the thesis, we show the results of our study where we investigated the influence of selected plant polyphenols and polyphenolic extracts on the in vitro growth and chondrogenic differentiation of mesenchymal stem/ stromal cells. The aim of this thesis is the evaluation of the influence of the two polyphenolic compounds (resveratrol in quercetin) and two polyphenolic extracts (Pycnogenol® and Belinal®) on the properties of human mesenchymal stem/ stromal cells in vitro. Human trabecular bone mesenchymal stem/ stromal cells derived from patients with osteoarthritis and healthy donors were treated with these compounds under inflammatory and non-inflammatory conditions. There were no significant effect of these polyphenolic compounds on the chondrogenesis of the mesenchymal stem/ stromal cells from healthy donors. However, Belinal® significantly improved the chondrogenesis of mesenchymal stem/ stromal cells derived from osteoarthritis patients in comparison with resveratrol under non-inflammatory conditions. Under inflammatory conditions, of all the compounds tested in our study, only Belinal® improved chondrogenesis of mesenchymal stem/ stromal cells derived from osteoarthritis patients. The results of this thesis demonstrate the potential of Belinal® polyphenolic compounds in improving the properties of human mesenchymal stem/ stromal cells in vitro and represent the basis for further studies using these compounds to develop effective cell therapies for osteoarthritis.
Keywords:	osteoarthritis, mesenchymal stem/ stromal cells, chondrogenic differentiation, proinflammatory cytokines, plant polyphenols, cartilage regeneration

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