|Tipo di tesi||Tesi di laurea magistrale|
|Titolo||Microvescicole da cellule staminali: isolamento, caratterizzazione e potenziale anti- cancro|
|Titolo in inglese||Stem cells-derived microvesicles: isolation, characterization and anti-cancer potential|
|Struttura||Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze|
|Corso di studi||MEDICINA E CHIRURGIA (D.M.270/04)|
|Data inizio appello||2017-10-17|
|Disponibilità||Accessibile via web (tutti i file della tesi sono accessibili)|
Le cellule stromali mesenchimali (MSC) sono cellule progenitrici dotate di elevato potenziale replicativo e della capacità di differenziare in diversi tipi cellulari.
Mesenchymal stromal cells (MSCs) are a population of multipotent progenitor cells that retain a proliferative potential and can differentiate into a variety of cell types. Their possible applications have been extensively investigate during the last few years, focusing primarily on their immunomodulatory and regenerative or tissue repair potential. In addition, they can be easily genetically manipulated and are able to migrate specifically to tumors and metastatic sites when systemically administered. These characteristics make MSCs an ideal vector to deliver anti-cancer agents in tumor sites. In particular, gene-engineered MSCs that express TNF-related apoptosis-inducing ligand (TRAIL) demonstrated a significant anti-tumor effects in several cancer models, such as pancreatic cancer and sarcoma. TRAIL is a member of the TNF super-family and is a transmembrane protein that plays a fundamental role in immune surveillance inducing apoptosis in cancer cells, while sparing most of the other cell types. This characteristic makes TRAIL a promising anti-cancer agent, but clinical applications of soluble recombinant human TRAIL have been hampered by the short half-life and the development of TRAIL-resistant cancer cell populations. In recent years, several studies showed that the secretion of bioactive factors is thought to play a predominant role in the therapeutic action of MSC and, in particular, MSC-derived extracellular vesicles (EVs) could mediate some biological functions conventionally attributed to MSC. EVs are membrane vesicles enclosed in a lipid bilayer containing cytosol and released from cells. Due to their capacity to transfer a rich cargo of proteins, lipids and nucleidic acids to other cells, thereby influencing the recipient cell function, EV play a role in intercellular communication. Moreover, Since EV are stable and have a lower risk of immune rejection following systemic administration, the possibility of their therapeutic use as drug-delivery systems has been raised. Based on these considerations, in this study we improved a differential centrifugation-based protocol for isolation of microvesicles (MVs) derived from TRAIL-armed human AD-MSC. MV were analyzed by flow cytometry and their cancer cell-killing efficacy was demonstrated by in vitro tests. The protocol we proposed has been proved to be suitable for isolation of MSC-derived EVs and these preliminary results indicate that microvesicles derived from TRAIL-armed AD-MSC are able to transport TRAIL molecules and to induce apoptosis of cancer cells, showing their potential as anti-cancer therapy.