Musculoskeletal tissue regeneration by human non-embryonic stem cells

Pisciotta, Alessandra (2014) Musculoskeletal tissue regeneration by human non-embryonic stem cells, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze biomediche, 26 Ciclo. DOI 10.6092/unibo/amsdottorato/6203.
Documenti full-text disponibili:
Documento PDF (English) - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Download (5MB) | Anteprima


The aim of this thesis was to investigate the regenerative potential of alternative sources of stem cells, derived from human dental pulp (hDPSCs) and amniotic fluid (hAFSCs) and, specifically, to evaluate their capability to be committed towards osteogenic and myogenic lineages, for the eventual applicability of these stem cells to translational strategies in regenerative medicine of bone and skeletal muscle tissues. The in vitro bone production by stem cells may represent a radical breakthrough in the treatment of pathologies and traumas characterized by critical bone mass defects, with no medical or surgical solution. Human DPSCs and AFSCs were seeded and pre-differentiated on different scaffolds to test their capability to subsequently reach the osteogenic differentiation in vivo, in order to recover critical size bone defects. Fibroin scaffold resulted to be the best scaffold promoting mature bone formation and defect correction when combined to both hDPSCs and hAFSCs. This study also described a culture condition that might allow human DPSCs to be used for human cell therapy in compliance with good manufacturing practices (GMPs): the use of human serum (HS) promoted the expansion and the osteogenic differentiation of hDPSCs in vitro and, furthermore, allowed pre-differentiated hDPSCs to regenerate critical size bone defects in vivo. This thesis also showed that hDPSCs and hAFSCs can be differentiated towards the myogenic lineage in vitro, either when co-cultured with murine myoblasts and when differentiated alone after DNA demethylation treatment. Interestingly, when injected into dystrophic muscles of SCID/mdx mice - animal model of Duchenne Muscular Dystrophy (DMD) - hDPSCs and hAFSCs pre-differentiated after demethylating treatment were able to regenerate the skeletal muscle tissue and, particularly, to restore dystrophin expression. These observations suggest that human DPSCs and AFSCs might be eventually applied to translational strategies, in order to enhance the repair of injured skeletal muscles in DMD patients.

Tipologia del documento
Tesi di dottorato
Pisciotta, Alessandra
Dottorato di ricerca
Scuola di dottorato
Scienze mediche e chirurgiche cliniche
Settore disciplinare
Settore concorsuale
Parole chiave
human dental pulp stem cells, human amniotic fluid stem cells, bone regeneration, skeletal muscle regeneration, Duchenne muscular dystrophy, human serum, scaffold
Data di discussione
23 Gennaio 2014

Altri metadati

Statistica sui download

Gestione del documento: Visualizza la tesi