In recent years, the Extracellular vesicles (EVs), tiny membraneous-derived vesicles filled with proteins, genetic materials (DNAs, miRNAs etc..), lipids and carbohydrates, were described as implicated in physio-pathological processes and in intercellular communication. Therefore, some of them have been indicated as potential useful therapeutic tools against a wide range of pathologies, included the Cardiovascular diseases (CVDs), as they could exert paracrine beneficial effects on the reactivation of the endogenous regenerative programme of the heart muscle. The aim of this thesis, is to exploit the secretome - conditioned medium (CMs) and the Exosome-rich fraction (EXOs), a particular EVs subgroup - of two stromal cell types: the II trimester fetal stem cells withdrawn during prenatal screening and the III trimester perinatal stem cells withdrawn at term performing c-sections, both submitted to normoxic / hypoxic preconditionings, to evaluate their potential regenerative effects. The experimental results obtained, showed in the ECM components especially in the Fetal hypoxic Exosome-rich fraction condition, an increase in pathways regarding anti-fibrotic, anti-inflammatory and angiogenesis processes highlighting their implications in the intercellular communication and thus giving useful insights for future therapeutic applications, not only for CVDs but for other pathologies too.
"Analisi proteomica del secretoma di cellule staminali fetali e perinatali (CM) e vescicole extracellulari (EVs) per indagare il loro potenziale rigenerativo". Negli ultimi anni, le vescicole extracellulari (EVs), minuscole vescicole di derivazione membrana riempite di proteine, materiali genetici (DNAs, miRNAs ecc.), lipidi e carboidrati, sono state descritte come implicate nei processi fisiopatologici e nella comunicazione intercellulare. Pertanto, alcuni di essi sono stati indicati come potenziali strumenti terapeutici utili contro un'ampia gamma di patologie, comprese le malattie cardiovascolari (CVDs), in quanto potrebbero esercitare effetti paracrini benefici sulla riattivazione del programma rigenerativo endogeno del muscolo cardiaco. Lo scopo di questa tesi, è quello di sfruttare il secretoma - mezzo condizionato (CMs) e la frazione esosomiale arricchita (EXOs), un particolare sottogruppo di EVs - di due tipi di cellule stromali: le cellule staminali fetali del II trimestre prelevate durante lo screening prenatale e le cellule staminali perinatali del III trimestre prelevate a termine eseguendo cesarei, entrambe sottoposte a precondizionamenti normossici / ipossici, per valutarne i potenziali effetti rigenerativi. I risultati sperimentali ottenuti, hanno evidenziato nelle componenti ECM soprattutto nella frazione esosomiale arricchita della condizione fetale ipossica, un aumento dei percorsi riguardanti i processi antifibrotici, antinfiammatori e angiogenetici evidenziandone le implicazioni nella comunicazione intercellulare e dando così utili spunti per future terapie applicazioni, non solo per CVDs ma anche per altre patologie.
"Proteomic analysis of fetal and perinatal stem cell secretome (CM) and extracellular vescicles (EVs) to investigate their regenerative potential"
BINETTI, NICOLAS
2019/2020
Abstract
In recent years, the Extracellular vesicles (EVs), tiny membraneous-derived vesicles filled with proteins, genetic materials (DNAs, miRNAs etc..), lipids and carbohydrates, were described as implicated in physio-pathological processes and in intercellular communication. Therefore, some of them have been indicated as potential useful therapeutic tools against a wide range of pathologies, included the Cardiovascular diseases (CVDs), as they could exert paracrine beneficial effects on the reactivation of the endogenous regenerative programme of the heart muscle. The aim of this thesis, is to exploit the secretome - conditioned medium (CMs) and the Exosome-rich fraction (EXOs), a particular EVs subgroup - of two stromal cell types: the II trimester fetal stem cells withdrawn during prenatal screening and the III trimester perinatal stem cells withdrawn at term performing c-sections, both submitted to normoxic / hypoxic preconditionings, to evaluate their potential regenerative effects. The experimental results obtained, showed in the ECM components especially in the Fetal hypoxic Exosome-rich fraction condition, an increase in pathways regarding anti-fibrotic, anti-inflammatory and angiogenesis processes highlighting their implications in the intercellular communication and thus giving useful insights for future therapeutic applications, not only for CVDs but for other pathologies too.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/12305