Varnost in učinkovitost mezenhimskih/stromalnih matičnih celic pri zdravljenju akutne bolezni presadka zoper gostitelja in kroničnih vnetnih črevesnih bolezni: sistematični pregled in meta-analiza

Mušić, Ajla (author), Jeras, Matjaž (mentor)

Ozadje: Akutna bolezen presadka zoper gostitelja (aGvHD) je stanje, pri katerem celice T darovalca, v odzivu na aloantigene prejemnika, povzročijo disregulacijo citokinske kaskade in delujejo citotoksično na prejemnikova tkiva. Predstavlja enega od najpogostejših, v določenih primerih tudi življenje ogrožajočih zapletov po alogenski presaditvi krvotvornih matičnih celic. Kronične vnetne črevesne bolezni (KVČB) pa so ponavljajoča se vseživljenjska patološka stanja, pri katerih aktivirane imunske celice in vnetni citokini povzročajo poškodbe črevesnega tkiva in nenormalen sistemski imunski odziv. Izsledki številnih raziskav so pokazali veliko stopnjo učinkovitosti in varnosti mezenhimskih/ stromalnih matičnih celic (MSC) pri zdravljenju tkivnih poškodb in uravnavanju imunskega odziva, predvsem zaradi njihovih imunomodulatornih, pa tudi multipotentnih regenerativnih lastnosti. Pri tem je zlasti pomembna njihova sposobnost tarčnega lociranja poškodovanih tkiv, kjer nato proizvajajo protivnetne parakrine dejavnike. Namen našega dela je bil, s pomočjo sistematičnega pregleda objavljenih raziskav in meta-analize njihovih rezultatov, potrditi varnost in učinkovitost zdravljenja z MSC. Metode: Izvedli smo sistematični pregled literature v prosto dostopnih spletnih podatkovnih zbirkah. Iz pridobljenih zadetkov smo, glede na predhodno določene kriterije, izbrali študije s kontrolnimi skupinami, serije primerov ter poročila posameznih primerov. V izbrane študije sta bili vključeni tako odrasla kot pediatrična populacija bolnikov. Meta-analize smo izvedli s pomočjo programske opreme Review Manager 5.4 ter rezultate predstavili v obliki drevesnih diagramov. Rezultati: V meta-analizo rezultatov kliničnih študij s kontrolno skupino smo v primeru aGvHD vključili 4, v primeru KVČB pa 5 študij. Uspelo nam je dokazati statistično značilno zmanjšanje smrtnosti bolnikov, ki so prejemali MSC za zdravljenje aGvHD, medtem ko primerjave drugih izbranih parametrov niso pokazale statistično značilnih razlik. Prav tako nismo uspeli dokazati statistično značilnih razlik pri primerjavi različnih parametrov v primeru zdravljenja KVČB z MSC. Pomembno je tudi dejstvo, da zaradi heterogenosti raziskav nismo mogli vključiti vseh v meta-analizo vsakega posameznega parametra. Sklep: Terapije z MSC nedvomno lahko pomagajo pri zdravljenju aGvHD in KVČB. Pri tem pa treba izpostaviti dejstvo, da stanje bolnikov pomembno vpliva na določitev odmerkov celičnega zdravila in način njihove aplikacije, kar je še posebej opazno v primeru KVČB.

• Language: Slovenian
• Keywords: mezenhimske/ stromalne matične celice, akutna bolezen presadka zoper gostitelja, kronične vnetne črevesne bolezni, Crohnova bolezen, ulcerozni kolitis
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-144938
• Publication date in RUL: 24.03.2023

MUŠIĆ, Ajla, 2023, Varnost in učinkovitost mezenhimskih/stromalnih matičnih celic pri zdravljenju akutne bolezni presadka zoper gostitelja in kroničnih vnetnih črevesnih bolezni: sistematični pregled in meta-analiza [online]. Master’s thesis. [Accessed 23 March 2025]. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=144938

Secondary language

• Language: English
• Title: Safety and efficacy of mesenchymal/stromal stem cells in the treatment of acute graft-versus-host disease and chronic inflammatory bowel diseases: systematic review and meta-analysis

Abstract

Background: Acute graft-versus-host disease (aGvHD) is a condition in which donor T cells, in response to recipient alloantigens, cause dysregulation of the cytokine cascade and act cytotoxicly on recipient tissues. It represents one of the most common, in certain cases even life-threatening complications after allogeneic hematopoietic stem cell transplantation. Chronic inflammatory bowel diseases (IBD) are recurrent lifelong pathological conditions in which activated immune cells and inflammatory cytokines cause intestinal tissue damage and an abnormal systemic immune response. The results of many studies have shown a high level of efficiency and safety of mesenchymal/stromal stem cells (MSC) in the treatment of tissue damage and regulation of the immune response, mainly due to their immunomodulatory as well as multipotent regenerative properties. Particularly important here is their ability to target damaged tissues, where they then produce anti-inflammatory paracrine factors. The aim of our work was to confirm the safety and effectiveness of MSC treatment through a systematic review of published research and a meta-analysis of their results. Methods: We conducted a systematic review of the literature in accessible online databases. From the obtained results, according to previously defined criteria, we selected studies with control groups, case series, and individual case reports. Both adult and pediatric patient populations were included in the selected studies. Meta-analyses were performed using the software Review Manager 5.4, and the results were presented in the form of tree diagrams. Results: In the meta-analysis of the results of clinical studies with a control group, we included 4 studies in the case of aGvHD and 5 studies in the case of IBD. We were able to demonstrate a statistically significant reduction in mortality in patients who received MSCs for the treatment of aGvHD, while comparisons of other selected parameters did not show statistically significant differences. We also failed to demonstrate statistically significant differences when comparing various parameters in the case of IBD treatment with MSCs. Also important is the fact that, due to the heterogeneity of the research, we could not include all of them in the meta-analysis of each individual parameter. Conclusion: MSC therapies can undoubtedly help in the treatment of aGvHD and IBD. However, it is important to highlight the fact that the condition of the patients has a significant impact on the determination of the doses of the cellular drug and the way in which they are administered, which is particularly noticeable in the case of IBD.

• Keywords: mesenchymal/stromal cells, acute graft-versus-host disease, chronic inflammatory bowel disease, Crohn’s disease, ulcerative colitis