Mesenchymal stem or stromal cells (MSCs) are a specific type of adult stem cells with an extensive proliferation and differentiation potential towards specialized cells developing from the mesoderm. MSCs are also characterized by paracrine function through the release of multiple growth factors, chemokines and cytokines. MSCs play as sentinel that feel the microenvironment and act consequently, switching from a pro-inflammatory phenotype to an immunosuppressive phenotype according to the signals they receive. In the present work the existence and the role of MSCs in the pathogenesis and potential therapy of selected gynecological diseases with an inflammatory component as uterine leiomyoma, cervical intraepithelial neoplasia (CIN), and in primary myopathies, as Duchenne Muscular Dystrophy (DMD) were evaluated. In the first study, progenitor cells were identified both in leiomyomas and normal myometrium, and the correlation between these cells and inflammation in leiomyoma onset has been investigated. The data suggest that the upregulation of cytokines related to chronic inflammation in leiomyoma progenitors could favour a microenvironment suitable for the onset of this pathology. In the second study, MSCs from cervix of young (yC-MSCs) and old patients (oC-MSCs) were isolated and results show as their immunobiology is affected by the age of donors, influencing in turn the regression rate of CIN. In addition, in the crosstalk with HeLa cells, yC-MSCs play an anti-tumoral role sustaining an acute inflammatory environment. The goal of the third study was to find a correct strategy to enhance the production of dystrophin protein in DMD through gene therapy. Therefore, myoblasts isolated from DMD donor were transduced with green fluorescent protein (GFP) and a lentiviral vector expressing the snRNA to induce exon skipping; data indicate that transduced myoblasts were able to perform myogenic differentiation expressing a functional dystrophin protein.
Le cellule staminali mesenchimali (MSCs) sono un tipo specifico di cellule staminali adulte con un elevato potenziale proliferativo e differenziativo verso cellule specializzate di derivazione mesodermica. Le MSCs svolgono anche una funzione paracrina attraverso il rilascio di molteplici fattori di crescita, chemochine e citochine. Le MSCs si comportanto da sentinelle che percepiscono il microambiente e agiscono di conseguenza, passando da un fenotipo pro-infiammatorio ad uno immunosoppressivo in base ai segnali che ricevono. Nel seguente lavoro sono valutati l’esistenza e il ruolo delle MSCs nella patogenesi e nella potenziale terapia di selezionate patologie ginecologiche con una componente infiammatoria come il leiomioma uterino, la neoplasia intraepiteliale cervicale (CIN) e in miopatie primarie, quali la Distrofia Muscolare di Duchenne (DMD). Nel primo studio, sono state identificate le cellule progenitrici nel leiomioma e nel miometrio sano ed è stata investigata la correlazione tra tali cellule e l’infiammazione nell’insorgenza del leiomioma. I dati suggeriscono che una overespressione di citochine relative all’infiammazione cronica nei progenitori del leiomioma potrebbe favorire un microambiente adeguato per l’insorgenza di questa patologia. Nel secondo studio, le MSCs sono state isolate da cervici di pazienti giovani (yC-MSCs) e pazienti vecchie (oC-MSCs) e i risultati mostrano come la loro immunobiologia sia condizionata dall’età dei donatori, influenzando anche il tasso di regressione della CIN. Inoltre, nel crosstalk con le cellule HeLa, yC-MSCs svolgono maggiormente un ruolo anti-tumorale sostenendo un’infiammazione acuta. L’obiettivo del terzo studio è stato quello di trovare una corretta strategia per aumentare la produzione di distrofina nella DMD mediante terapia genica. Pertanto, i mioblasti isolati da donatori di DMD sono stati trasdotti con la proteina fluorescente verde (GFP) e un vettore lentivirale esprimente l’snRNA per indurre il salto dell’esone; i dati indicano che i mioblasti trasdotti erano abili a differenziare in senso miogenico esprimendo la distrofina funzionale.
Mesoderm stem cells and inflammation: role in the Pathogenesis and potential therapy of selected Gynecological Deseases and primary Myopathies / Caffarini, Miriam. - (2019 Mar 15).
Mesoderm stem cells and inflammation: role in the Pathogenesis and potential therapy of selected Gynecological Deseases and primary Myopathies
CAFFARINI, MIRIAM
2019-03-15
Abstract
Mesenchymal stem or stromal cells (MSCs) are a specific type of adult stem cells with an extensive proliferation and differentiation potential towards specialized cells developing from the mesoderm. MSCs are also characterized by paracrine function through the release of multiple growth factors, chemokines and cytokines. MSCs play as sentinel that feel the microenvironment and act consequently, switching from a pro-inflammatory phenotype to an immunosuppressive phenotype according to the signals they receive. In the present work the existence and the role of MSCs in the pathogenesis and potential therapy of selected gynecological diseases with an inflammatory component as uterine leiomyoma, cervical intraepithelial neoplasia (CIN), and in primary myopathies, as Duchenne Muscular Dystrophy (DMD) were evaluated. In the first study, progenitor cells were identified both in leiomyomas and normal myometrium, and the correlation between these cells and inflammation in leiomyoma onset has been investigated. The data suggest that the upregulation of cytokines related to chronic inflammation in leiomyoma progenitors could favour a microenvironment suitable for the onset of this pathology. In the second study, MSCs from cervix of young (yC-MSCs) and old patients (oC-MSCs) were isolated and results show as their immunobiology is affected by the age of donors, influencing in turn the regression rate of CIN. In addition, in the crosstalk with HeLa cells, yC-MSCs play an anti-tumoral role sustaining an acute inflammatory environment. The goal of the third study was to find a correct strategy to enhance the production of dystrophin protein in DMD through gene therapy. Therefore, myoblasts isolated from DMD donor were transduced with green fluorescent protein (GFP) and a lentiviral vector expressing the snRNA to induce exon skipping; data indicate that transduced myoblasts were able to perform myogenic differentiation expressing a functional dystrophin protein.File | Dimensione | Formato | |
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