Terapevtska in diagnostična uporaba človeških eksosomov: sistematični pregled in analiza globalnih trendov izvajanja kliničnih raziskav

Vedlin, Vid (avtor), Jeras, Matjaž (mentor)

Ozadje: Eksosomi so membranski vezikli, ki jih celice izločajo v zunajcelični prostor. Sodelujejo pri številnih fizioloških in patoloških procesih, kot so: imunski odziv, obnavljanje tkiv, vnetje in rak. Udeleženi so tudi v medcelični komunikaciji, saj prenašajo številne signalne molekule: proteine, lipide in nukleinske kisline (DNA, mRNA, mikro RNA). Tovor, ki ga eksosomi prenašajo, odraža sestavo celic iz katerih izvirajo, zato so pomemben vir raznolikih diagnostičnih označevalcev. Vse več kliničnih raziskav se ukvarja predvsem s terapevtsko rabo eksosomov matičnih celic, ki imajo številne prednosti v primerjavi s samimi celicami. Metode: Sistematični pregled literature smo izvedli v bibliografskih spletnih bazah, Clinicaltrials.gov, Cochrane library ter MEDLINE. Za analizo smo izbrali tiste raziskave, v okviru katerih so proučevali normalne in spremenjene človeške eksosome za terapevtske ter diagnostične namene. Pri slednjih smo se omejili na rakava obolenja prostate in pljuč. Zaradi velikega števila še potekajočih študij smo izvedli analizo globalnih trendov izvajanja omenjenih raziskav. Izbrane parametre kot so število preiskovancev, vrsta uporabljenih eksosomov, itd., smo prikazali v obliki grafov. Značilnosti vseh analiziranih raziskav pa smo predstavili v preglednicah. Rezultati: S sistematičnim pregledom smo pridobili skupno 53 raziskav, od katerih jih je 30 obravnavalo terapevtsko, 23 pa diagnostično rabo človeških eksosomov. V terapevtske namene največkrat uporabljajo eksosome iz mezenhimskih/ stromalnih matičnih celic, s katerimi eksperimentalno tretirajo predvsem bolezni dihal, neoplazme, nevrološke in kožne bolezni. Večina analiziranih kliničnih preskušanj je bila odprtih, nerandomiziranih in v fazi I kliničnih raziskav. V povprečju so te raziskave trajale 1,9 let. V primeru diagnostične rabe eksosomov pa smo zasledili največ kohortnih študij. Veliko je takih, ki validirajo teste na podlagi eksosomskih označevalcev. Kot nove diagnostične označevalce pa raziskujejo predvsem eksosomske mikro RNA. Tovrstne raziskave trajajo v povprečju 3 leta. Sklep: Področje uporabe eksosomov je novo in nakazuje njihov velik potencial za terapevtsko in diagnostično uporabo, pri čemer je slednja pravzaprav že postala realnost.

• Jezik: Slovenski jezik
• Ključne besede: eksosomi, terapevtska uporaba, diagnostika, rak prostate, rak pljuč
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2022
• PID: 20.500.12556/RUL-134975
• Datum objave v RUL: 16.02.2022

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Therapeutic and diagnostic use of human exosomes: Systematic review and analysis of global trends in performing clinical studies

Izvleček

Background: Exosomes are membrane vesicles which cells secrete into the extracellular space. They are involved in many physiological processes, like immune response and tissue regeneration, as well as pathological processes, e.g. inflammation and cancer. They are also involved in intercellular communication, as they carry many signaling molecules, such as proteins, lipids and nucleic acids (DNA, mRNA, microRNA). Due to their load, which reflects the composition of the originating cell, they are an important source of various diagnostic markers. More and more clinical research is conducted in the therapeutic use of exosomes, which have many advantages especially compared to stem cells from which they originate. Methods: Systematic review of literature has been performed using the following online bibliographic databases: Clinicaltrials.gov, Cochrane library and MEDLINE. We have selected those clinical research studies in which human exosomes or altered human exosomes were used for therapeutic or diagnostic purposes. In the latter case, we limited ourselves to prostate and lung cancers. Due to a large number of ongoing studies, we performed the analysis of their global trends. Selected parameters, such as number of participating subjects, types of exosomes used, etc., were presented graphically. The selected properties of all studies were presented in tables. Results: Following stringent inclusion/ exclusion criteria, 53 studies were selected for analysis. Thirty of them were dealing with therapeutic and 23 with diagnostic use of human exosomes. In the first group the most commonly used exosomes in clinics were derived from mesenchymal stem cells, and were mostly investigated in treatment of respiratory diseases, neoplasms, and neurological and skin diseases. Most clinical trials were open-label, non-randomised, and phase I. Therefore, the average length of a clinical trial in this group is 1,9 years. Most of the analysed diagnostic studies were cohort studies. There were also many validating diagnostic tests based on exosomal markers. In terms of new diagnostic markers, microRNAs were those being mainly investigated. On average, this type of research takes 3 years. Conclusion: The field of exosomes is rather new, and holds a great potential for their therapeutic and diagnostic use.

• Ključne besede: exosomes, therapeutic use, diagnostics, prostate cancer, lung cancer