Ricerc@Sapienza

Mesenchymal stem cells (MSC) have piqued worldwide interest for their extensive potential to treat a large array of clinical indications, their unique and controversial immunogenic and immune modulatory properties allowing ample discussions and debates for their possible applications. Emerging data demonstrating that the interaction of biomaterials and physical cues with MSC can guide their differentiation into specific cell lineages also provide new interesting insights for further MSC manipulation in different clinical applications.

Vascularization is a crucial factor when approaching any engineered tissue. Vascular
wall–mesenchymal stem cells are an excellent in vitro model to study vascular remodeling due to
their strong angiogenic attitude. This study aimed to demonstrate the angiogenic potential of
experimental highly porous scaffolds based on polylactic acid (PLA) or poly‐e‐caprolactone (PCL)
doped with calcium silicates (CaSi) and dicalcium phosphate dihydrate (DCPD), namely PLA‐
10CaSi‐10DCPD and PCL‐10CaSi‐10DCPD, designed for the regeneration of bone defects. Vascular

Dental pulp has been revealed as an accessible and a rich source of mesenchymal stem cells (MSCs) and its biological potential is currently under intense investigation. MSCs from dental pulp stem cells (DPSCs) have been indicated as a heterogeneous population oriented not only in repairing dentine but also in maintaining vascular and nervous homeostasis of the teeth. We sought to verify the phenotype of cells isolated from dental pulp of young donors and to investigate in vitro their role as pericyte-like cells.

Neuropeptide Y (NPY), a powerful neurotransmitter of the central nervous system, is a key regulator of angiogenesis and biology of adipose depots. Intriguingly, its peripheral vascular and angiogenic powerful activity is strictly associated to platelets, which are source of clinical hemoderivates, such as platelet lysate (PL), routinely employed in several clinical applications as wound healing, and to preserve ex vivo the progenitor properties of the adipose stromal cells pool.

Peribiliary glands (PBGs) represent the niche of biliary tree stem/progenitor cells (BTSCs) [1]. BTSCs are multipotent stem cells able to differentiate into hepatocytes, cholangiocytes, and pancreatic islets. Primary sclerosing cholangitis (PSC) is a chronic inflammation involving extra-hepatic biliary tree, and is complicated by the risk of cholangiocarcinoma (CCA) development [2]. We aimed to evaluate the involvement of PBGs and BTSCs in PSC and their role in CCA insurgence [2].

Primary biliary cholangitis (PBC) primarily targets cholangiocytes and is characterized by liver fibrosis and biliary proliferation. Activation of the secretin (Sct)/secretin receptor (SR) axis, expressed only by cholangiocytes, increases biliary proliferation, liver fibrosis, and bicarbonate secretion. We evaluated the effectiveness of SR antagonist treatment for early-stage PBC. Male and female dominant-negative TGF-β receptor II (dnTGF-βRII) (model of PBC) and wild-type mice at 12 wk of age were treated with saline or the SR antagonist, Sec 5-27, for 1 wk.

Gliomas represent over 50% of tumors occurring in children. Evidence suggests that glioma stem cells (GSCs), maintained by the transforming growth factor-beta (TGF-β1) pathway, and vascularization substantially contribute to tumor aggressiveness. The identification of important angiogenic factors such as vascular endothelial growth factor (VEGF) may represent a crucial step in the therapeutic approach against tumor growth and metastatic diffusion. The aim of this study was to identify the expression of TGF-β1, VEGF and VEGF-receptors in brain gliomas.

Dkk-3 is a member of the dickkopf protein family of secreted inhibitors of the Wnt pathway, which has been shown to enhance angiogenesis. The mechanism underlying this effect is currently unknown. Here, we used cultured HUVECs to study the involvement of the TGF-? and VEGF on the angiogenic effect of Dkk-3. Addition of hrDkk-3 peptide (1 or 10 ng/ml) to HUVECs for 6 or 12 h enhanced the intracellular and extracellular VEGF protein levels, as assessed by RTPCR, immunoblotting, immunocytochemistry and ELISA.

Myeloid-derived suppressor cells (MDSCs) support tumor development by stimulation of angiogenesis and immune response inhibition. In our previous study, we showed that interferon lambda 2 (IFN-?2), secreted by MDSCs, enhances production of pro-angiogenic factors by cancer cells via phosphorylation of STAT3 and therefore promotes blood vessels formation. In the present study IFN-?2 level was evaluated by ELISA in serum of tumor-bearing mice, whereas its expression in MDSCs isolated from the lungs with metastatic tumors and normal lungs was assessed by qPCR.

The last two decades have seen the development of effective therapies, which have saved the lives of a large number of melanoma patients. However, therapeutic options are still limited for patients without BRAF mutations or in relapse from current treatments, and severe side effects often occur during therapy. Thus, additional insights to improve treatment efficacy with the aim to decrease the likelihood of chemoresistance, as well as reducing side effects of current therapies, are required.