Papers by Laura Pierdomenico
Long-term stability of arthroplasty prosthesis depends on the integration between the bone tissue... more Long-term stability of arthroplasty prosthesis depends on the integration between the bone tissue and the implanted biomaterials, which requires the contribution of osteoblastic precursors and their continuous differentiation into the osteoblastic phenotype. Classically, these interactions are tested in vitro using mesenchymal stem cells (MSCs) isolated and ex vivo expanded from bone marrow aspirates. Human adipose tissue-derived stromal cells (AMSCs) may be a more convenient source of MSCs, according to their abundance and accessibility, but no data are available on their in vitro interactions with hard biomaterials. The aim of this work is to compare the osteogenic potential of human AMSCs and bone marrow-derived MSCs (BMMSCs) and to evaluate their response to Ti6Al4V alloy in terms of adhesion, proliferation and differentiation features, using the human osteosarcoma cell line SaOS-2 for comparison. The overall results showed that AMSCs have the same ability to produce bone matrix as BMMSCs and that Ti6Al4V surfaces exhibit an osteoinductive action on AMSCs, promoting their differentiation into functional osteoblasts and increasing bone formation. In conclusion, adipose tissue is a promising autologous source of osteoblastic cells with important clinical implications for bone tissue engineering.
Italian journal of anatomy and embryology, 2017
Neural Regeneration Research, 2020
In the pathophysiology of neurodegenerative disorders, the role of misfolded protein deposition l... more In the pathophysiology of neurodegenerative disorders, the role of misfolded protein deposition leading to neurodegeneration has been primarily discussed. In the last decade, however, it has been proposed a parallel involvement of innate immune activation, chronic inflammation and adaptive immunity in the neurodegeneration mechanisms triggered by proteinopathies. New insights in the neurodegenerative field strongly suggest a role for the immune system in the pathophysiology of neurodegenerative disorders. Therefore, the hypothesis underlining the modulation of the innate and the adaptive immune system in the events linked to brain deposition of misfolded proteins could open new perspectives in the setting of specific immunotherapeutic strategies for the treatment of neurodegenerative diseases. Therefore, we have reviewed the pathogenic hypothesis in neurodegenerative pathologies, underling the links between the deposition of misfolded protein mechanisms and the immune activation.
InTech eBooks, Sep 6, 2011
International Journal of Immunopathology and Pharmacology, Jul 1, 2005
Release of vascular endothelial growth factor (VEGF) and other candidate angiogenic factors such ... more Release of vascular endothelial growth factor (VEGF) and other candidate angiogenic factors such as basic fibroblast growth factor and transforming growth factor B, may playa role in sustaining neoplastic cell proliferation and tumor growth. We evaluated VEGF expression and synthesis in the two erythromegakaryocytic cell lines B1647, HEL and one megakaryocytic cell line M07 expressing erythroid markers. In this study RT-PCR was performed to evaluate VEGF expression and that of its receptor KDR; VEGF production was assayed by Elisa test and western blot analysis; sensitivity to VEGF was tested by thymidine incorporation. VEGF and its receptor KDR were expressed in B1647 and HEL, both as mRNAs and as proteins, while only KDR transcript was found in M07 cells. Only B1647 and HEL cells showed a strong spontaneous proliferating activity. In fact, measurable amounts of VEGF were present in the unstimulated cell medium, thus suggesting an autocrine production ofVEGF by B1647 and HEL cells, but not by M07, which was inhibited in mRNA-silencing conditions. This production could not be further boosted by other growth factors, whereas it was inhibited by TGF-~l. Finally, analysis of She signal transduction proteins following stimulation with VEGF indicated that only p46 was tyrosine phosphorylated. These data indicate that leukemic cells may be capable of autocrine production ofVEGF which, in turn, maintains cell proliferation, possibly mediated by She p46 phosphorylation. Vascular endothelial growth factor (VEGF), a potent inducer of angiogenesis and a stimulator of endothelial cell proliferation, differentiation and survival, is involved in the development of blood vessels during embryogenesis and promotes vascular permeability and migration of monocytes through endothelial tissue. It is a homo dimeric glycoprotein with a structural similarity to Platelet-Derived Growth Factor (PDGF), and can appear in five isoforms, two bound to the cell surface or to the extracellular matrix (189 and 206) and three soluble (121, 145 and 165) forms that induce proliferation of endothelial cells and in vivo angiogenesis (1). Production of VEGF is regulated by growth factors such as Fibroblast Growth Factor 4, PDGF, Tumor Necrosis Factor-a ((TNF-a), Transforming Growth Factor-B
Italian journal of anatomy and embryology, 2016
Impact of Research on Clinical Medicine and Basic Science Mesenchymal stem cell extracellular ves... more Impact of Research on Clinical Medicine and Basic Science Mesenchymal stem cell extracellular vesicles attenuate pulmonary hypertensive responses, but the most effective dose and mechanism of action are not known. Findings from the present study demonstrate that mesenchymal stem cell extracellular vesicles reverse severe pulmonary hypertension even when administered a low doses with a sustained effect for up to 3 weeks. Improvement in vascular remodeling is associated with a reduction in lung macrophages and an increase in the ratio of macrophages activated via the alternative versus the classical pathway (M2/M1). These findings suggest that mesenchymal stem cell extracellular vesicles may be an effective new therapy for treating pulmonary arterial hypertension due to their immunomodulatory effect on macrophages.
Pharmaceuticals, Feb 22, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
International Journal of Molecular Sciences, Nov 23, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Oncology, Nov 18, 2019
e recent introduction of the "precision medicine" concept in oncology pushed cancer research to f... more e recent introduction of the "precision medicine" concept in oncology pushed cancer research to focus on dynamic measurable biomarkers able to predict responses to novel anticancer therapies in order to improve clinical outcomes. Recently, the involvement of extracellular vesicles (EVs) in cancer pathophysiology has been described, and given their release from all cell types under specific stimuli, EVs have also been proposed as potential biomarkers in cancer. Among the techniques used to study EVs, flow cytometry has a high clinical potential. Here, we have applied a recently developed and simplified flow cytometry method for circulating EV enumeration, subtyping, and isolation from a large cohort of metastatic and locally advanced nonhaematological cancer patients (N � 106); samples from gender-and age-matched healthy volunteers were also analysed. A large spectrum of cancer-related markers was used to analyse differences in terms of peripheral blood circulating EV phenotypes between patients and healthy volunteers, as well as their correlation to clinical outcomes. Finally, EVs from patients and controls were isolated by fluorescence-activated cell sorting, and their protein cargoes were analysed by proteomics. Results demonstrated that EV counts were significantly higher in cancer patients than in healthy volunteers, as previously reported. More interestingly, results also demonstrated that cancer patients presented higher concentrations of circulating CD31+ endothelial-derived and tumour cancer stem cell-derived CD133 + CD326-EVs, when compared to healthy volunteers. Furthermore, higher levels of CD133 + CD326− EVs showed a significant correlation with a poor overall survival. Additionally, proteomics analysis of EV cargoes demonstrated disparities in terms of protein content and function between circulating EVs in cancer patients and healthy controls. Overall, our data strongly suggest that blood circulating cancer stem cell-derived EVs may have a role as a diagnostic and prognostic biomarker in cancer.
Nutrients
Extracellular vesicles (EVs) are a class of circulating entities that are involved in intercellul... more Extracellular vesicles (EVs) are a class of circulating entities that are involved in intercellular crosstalk mechanisms, participating in homeostasis maintenance, and diseases. Celiac disease is a gluten-triggered immune-mediated disorder, characterized by the inflammatory insult of the enteric mucosa following local lymphocytic infiltration, resulting in villous atrophy. The goal of this research was the assessment and characterization of circulating EVs in celiac disease patients, as well as in patients already on an adequate gluten-free regimen (GFD). For this purpose, a novel and validated technique based on polychromatic flow cytometry that allowed the identification and enumeration of different EV sub-phenotypes was applied. The analysis evidenced that the total, annexin V+, leukocyte (CD45+), and platelet (CD41a+) EV counts were significantly higher in both newly diagnosed celiac disease patients and patients under GFD compared with the healthy controls. Endothelial-derived ...
International Journal of Molecular Sciences
Recently, the protective and/or pathological role of virus-specific T cells in SARS-CoV-2 infecti... more Recently, the protective and/or pathological role of virus-specific T cells in SARS-CoV-2 infection has been the focus of many studies. We investigated the anti-spike IgG levels and SARS-CoV-2-specific T cells in 125 donors (90 vaccinated with four different vaccine platforms, 16 individuals with a previous natural infection, and 19 not vaccinated donors who did not report previous SARS-CoV-2 infections). Our data show that anti-spike IgG titers were similar between naturally infected subjects and those vaccinated with adenoviral vector vaccines. Of note, all immunized donors produced memory CD4+ and/or CD8+ T cells. A sustained polyfunctionality of SARS-CoV-2-specific T cells in all immunized donors was also demonstrated. Altogether, our data suggest that the natural infection produces an overall response like that induced by vaccination. Therefore, this detailed immunological evaluation may be relevant for other vaccine efforts especially for the monitoring of novel vaccines effec...
81° Congresso Nazionale SIGO, 2005
Le cellule mesenchimali staminali sono cellule multipotenti in grado di differenziare in tutti i ... more Le cellule mesenchimali staminali sono cellule multipotenti in grado di differenziare in tutti i tessuti connettivali maturi. Isolate inizialmente nel midollo osseo, dove giocano un ruolo chiave nel supportare l\u2019emopoiesi, sono state trovate come reservoir in molti tessuti maturi, quali la polpa dentale, il liquido sinoviale, il tessuto adiposo, il tessuto osseo trabecolare. Tutte queste popolazioni sono accomunate dall\u2019avere un caratteristico pattern antigenico e sono state analizzate per valutare il potenziale differenziativo in vivo e in vitro. Nell\u2019ambito della ricerca di fonti alternative al midollo osseo, abbbiamo focalizzato la nostra attenzione allo studio dei tessuti extraembrionali (membrana amniotica, membrana coriale) derivati da parti cesarei di neonati sani. Le popolazioni di cellule aderenti, di morfologia fibroblastoide isolate dalla membrana amniotica, dalla membrana coriale e dalle due membrane riunite e sono state caratterizzate immunofenotipicamente mediante saggio al citofluorimetro e i profili antigenici ottenuti confronati con quello delle cellule mesenchimali staminali derivate da midollo osseo. Tutte le popolazioni sono risultate omogeneamente positive per i marcatori mesenchimali caratteristici (CD105 ,CD73, CD29, CD44,CD166, α-smooth muscle actin) e negativi per i marcatori emopoietici (CD14, CD34, CD45). In particolare le cellule derivate dalla membrana amniotica mostrano una percentuale di omogeneit\ue0 superiore a quelle del midollo osseo. La staminalit\ue0 delle sopracitate cellule \ue8 stata, quindi, verificata attraverso saggi di differenziamennto in vitro in senso osteogenico, condrogenico, adipogenico, muscolare scheletrico e angiogenico, mediante opportuni terreni di induzione. L\u2019avvenuto differenziamento \ue8 stato valutato mediante colorazioni istochimiche, saggi immunoistochimici o RT-PCR; il potenziale angiogenico \ue8 stato invece analizzato mediante saggio di formazione di strutture simil-capillari su gel di composizione simile alla membrana basale (matrigel). I nostri dati indicano che la popolazione isolata dalle membrane fetali \ue8 in grado di differenziare non solo verso i classici tessuti connettivali maturi osteogenico e condrogenico, ma anche in senso muscolare scheletrico. Le cellule isolate da membrana amniotica hanno mostrato interessanti risulati nel differenziamento in senso adipogenico: dopo due settimane di induzione le cellule hanno formato degli aggregati secernenti gocce lipidiche, fenomeno mai osservato con le cellule derivate da midollo osseo. Interessanti dati emergono dal differenziamento in senso angiogenico: sia le cellule derivate dalla membrana amniotica che quelle derivate dalle membrane fetali mostrano una spontanea organizzazione in strutture simil-capillari e un\u2019 organizzazione pi\uf9 complessa dopo induzione con opportuno terreno, anche se la raggiungono con cinetiche differenti. I tessuti extraembrionali possono essere considerati una sorgente alternativa al midollo osseo interessante e per alcuni aspetti vantaggiosa: \ue8 un tessuto normalmente scartato che permette, invece, un elevato recupero cellulare, con un alto potenziale proliferativo e differenziativo e potr\ue0 verosimilmente diventare un valido strumento terapeutico nell\u2019ambito della medicina rigenerativa. BIBLIOGRAFIA Short B et al. Mesenchymal Stem Cells. Archives of Medical research 34 565-571. 2003 Muguruma Y. et al. In vivo and in vitro differentiation of myocytes from human bone marrow-derived multipotent progenitor cells. Experimental Hematology 31 1323-1330. 2003 Oswald J. et al. Mesenchymal Stem Cells can be differentiated into endothelial cells in vitro. Stem Cell 22:377-384. 2004 Pittenger MF et al. Multilineage Potential of Adult Human Mesenchymal Stem Cells. Science 284:143-147. 199
Journal of Oncology, 2020
Journal of Oncology, 2019
The recent introduction of the “precision medicine” concept in oncology pushed cancer research to... more The recent introduction of the “precision medicine” concept in oncology pushed cancer research to focus on dynamic measurable biomarkers able to predict responses to novel anticancer therapies in order to improve clinical outcomes. Recently, the involvement of extracellular vesicles (EVs) in cancer pathophysiology has been described, and given their release from all cell types under specific stimuli, EVs have also been proposed as potential biomarkers in cancer. Among the techniques used to study EVs, flow cytometry has a high clinical potential. Here, we have applied a recently developed and simplified flow cytometry method for circulating EV enumeration, subtyping, and isolation from a large cohort of metastatic and locally advanced nonhaematological cancer patients (N = 106); samples from gender- and age-matched healthy volunteers were also analysed. A large spectrum of cancer-related markers was used to analyse differences in terms of peripheral blood circulating EV phenotypes b...
Neural Regeneration Research, 2020
In the pathophysiology of neurodegenerative disorders, the role of misfolded protein deposition l... more In the pathophysiology of neurodegenerative disorders, the role of misfolded protein deposition leading to neurodegeneration has been primarily discussed. In the last decade, however, it has been proposed a parallel involvement of innate immune activation, chronic inflammation and adaptive immunity in the neurodegeneration mechanisms triggered by proteinopathies. New insights in the neurodegenerative field strongly suggest a role for the immune system in the pathophysiology of neurodegenerative disorders. Therefore, the hypothesis underlining the modulation of the innate and the adaptive immune system in the events linked to brain deposition of misfolded proteins could open new perspectives in the setting of specific immunotherapeutic strategies for the treatment of neurodegenerative diseases. Therefore, we have reviewed the pathogenic hypothesis in neurodegenerative pathologies, underling the links between the deposition of misfolded protein mechanisms and the immune activation.
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Papers by Laura Pierdomenico