Vpliv različnih aktivacijskih dejavnikov na imunomodulatorno delovanje mezenhimskih matičnih celic

Plaskan, Sara (avtor), Švajger, Urban (mentor)

Magistrsko delo obsega pregled literature na temo interakcije mezenhimskih matičnih celic (MSC) z imunskim sistemom, stimulacije MSC za namen indukcije imunosupresivnega fenotipa in uporabe MSC v klinični aplikaciji. Eksperimentalni del obsega rezultate in vitro stimulacije MSC z izbranimi aktivacijskimi dejavniki (AD) in s supernatanti mešane limfocitne reakcije (MLR) za namen ugotavljanja, kateri AD in supernatanti MLR izzovejo imunosupresivni fenotip MSC, ter primerjave obeh načinov stimulacije. Uspešnost indukcije imunosupresivnega fenotipa MSC smo določali s povečanjem izražanja PD-L1 in IDO. Določali smo tudi HLA-DR kot pokazatelja večje imunogenosti stimuliranih MSC. Kot najboljše kombinacije AD pri indukciji imunosupresivnega fenotipa MSC so se izkazale rapamicin/MPLA/TNFα/IFNγ za indukcijo izražanja PD-L1 in kombinaciji rapamicin/TNFα/IFNγ ter MPLA/TNFα/IFNγ pri indukciji izražanja IDO. Kombinacije AD niso inducirale bistveno večjega izražanja HLA-DR. Pri teh kombinacijah AD sklepamo na njihovo sinergistično ali aditivno delovanje pri indukciji imunosupresivnega fenotipa in ob pregledu literature trdimo, da je to prvi objavljen poskus stimulacije MSC s takšnimi kombinacijami AD. Kot najboljši supernatanti pri indukciji imunosupresivnega fenotipa MSC so se izkazali supernatanti MLR, ki so potekali v gojišču z dodatkom MPLA, ki ojača imunski odziv. Supernatanti MLR so dosegli primerljive rezultate kot AD in so se izkazali kot smiselna alternativa stimulaciji MSC z AD.

• Jezik: Slovenski jezik
• Ključne besede: mezenhimske matične celice, stimulacija, imunosupresivni fenotip
• Vrsta gradiva: Magistrsko delo/naloga
• Tipologija: 2.09 - Magistrsko delo
• Organizacija: BF - Biotehniška fakulteta
• Kraj izida: Ljubljana
• Založnik: [S. Plaskan]
• Leto izida: 2021
• PID: 20.500.12556/RUL-133096
• UDK: 606:61:57.083.3:602.9:611.018(043.2)
• COBISS.SI-ID: 84569603
• Datum objave v RUL: 11.11.2021

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: The effect of different activating factors on immunomodulatory activity of mesenchymal stem cells

Izvleček

This thesis encompasses an overview of publications examining interactions of mesenchymal stem cells (MSC) with the immune system, the induction of an immunosuppressive phenotype by MSC stimulation and clinical applications of MSC. We present the results of in vitro MSC stimulation with different activating factors (AD) and supernatants from mixed lymphocyte reactions (MLR). The aim was to evaluate which AD and MLR supernatants induce an immunosuppressive phenotype in MSC, and to compare them. The induction of an immunosuppressive phenotype was determined by enhanced expression of PD-L1 and IDO, and the increased immunogenicity was determined by expression of HLA-DR. The best combinations of AD were rapamycin/MPLA/TNFα/IFNγ for inducing expression of PD-L1, and the combinations rapamycin/TNFα/IFNγ and MPLA/TNFα/IFNγ for inducing expression of IDO. These combinations of AD also did not induce higher expression of HLA-DR. The immunosuppressive phenotype induction by these combinations of AD might be caused by their synergistic or additive behaviour. To our knowledge this is the first publication of MSC stimulation with these combinations of AD. The MLR supernatants best at inducing an immunosuppressive phenotype were those that took place in media with added MPLA, which strengthens the immune response. MLR supernatants achieved similar results as AD and could be a potential alternative to MSC stimulation with AD.

• Ključne besede: mesenchymal stem cells, stimulation, immunosuppressive phenotype