0000000001233737
AUTHOR
Marta Di Simone
An Analysis of the Immunomodulatory Properties of Human Spheroids from Adipose-Derived Stem Cells
Aims Current methods to induce tolerance following allotransplantation or in autoimmunity carry significant morbidity, and research is very active in investigating alternative methods which could minimize toxicity. Spheroids from adipose stem cells (SASCs) are increasingly gaining interest, they hold a great proliferative and differentiating potential. An immunomodulatory effect has not been investigated on SASCs yet. In this study, we analysed the immunomodulatory properties of SASCs and compared them to ADSCs. Main methods Adipose stem cells (SASCs and ADSCs) and peripheral blood mononuclear cells (PBMCs) were collected from healthy individuals. We analysed the cytokine production and pro…
Monoclonal Gammopathies and the Bone Marrow Microenvironment: From Bench to Bedside and Then Back Again
Multiple myeloma (MM) is an incurable hematologic malignancy characterized by a multistep evolutionary pathway, with an initial phase called monoclonal gammopathy of undetermined significance (MGUS), potentially evolving into the symptomatic disease, often preceded by an intermediate phase called “smoldering” MM (sMM). From a biological point of view, genomic alterations (translocations/deletions/mutations) are already present at the MGUS phase, thus rendering their role in disease evolution questionable. On the other hand, we currently know that changes in the bone marrow microenvironment (TME) could play a key role in MM evolution through a progressive shift towards a pro-inflammatory and…
Cell quality evaluation with gene expression analysis of spheroids (3D) and adherent (2D) adipose stem cells.
Adipose stem cells (ASCs) represent a reliable source of stem cells with a widely demonstrated potential in regenerative medicine and tissue engineering applications. New recent insights suggest that three-dimensional (3D) models may closely mimic the native tissue properties; spheroids from adipose derived stem cells (SASCs) exhibit enhanced regenerative abilities compared with those of 2D models. Stem cell therapy success is determined by “cell-quality”; for this reason, the involvement of stress signals and cellular aging need to be further investigated. Here, we performed a comparative analysis of genes connected with stemness, aging, telomeric length and oxidative stress, in 3D and 2D …
Characterisation of gd T cells infiltrating colorectal cancer
We have read with great interest the paper by de Vries et al 1 reporting on the immune landscape of colorectal cancer (CRC) by high-dimensional mass cytometry, flow cytometry and single cell RNA sequencing. Among clusters of immune cells infiltrating CRC, authors have identified two populations of γδ T cells: one programmed cell death protein 1 (PD-1)+ population is almost exclusively found in DNA mismatch repair (MMR)-deficient (d) tumours, constitutes up to 8.4% of CD45+ cells and has an activated phenotype, and a PD-1− counterpart with a resting phenotype, which is also found in colorectal normal mucosa and MMR-proficient (p) tumours. Using deconvolution of transcriptomic datasets and si…
γδ T cells and their clinical application in colon cancer
In recent years, research has focused on colorectal cancer to implement modern treatment approaches to improve patient survival. In this new era, γδ T cells constitute a new and promising candidate to treat many types of cancer because of their potent killing activity and their ability to recognize tumor antigens independently of HLA molecules. Here, we focus on the roles that γδ T cells play in antitumor immunity, especially in colorectal cancer. Furthermore, we provide an overview of small-scale clinical trials in patients with colorectal cancer employing either in vivo activation or adoptive transfer of ex vivo expanded γδ T cells and suggest possible combinatorial approaches to treat co…
Phenotypical and Functional Alteration of γδ T Lymphocytes in COVID-19 Patients: Reversal by Statins
(1) Background: statins have been considered an attractive class of drugs in the pharmacological setting of COVID-19 due to their pleiotropic properties and their use correlates with decreased mortality in hospitalized COVID-19 patients. Furthermore, it is well known that statins, which block the mevalonate pathway, affect γδ T lymphocyte activation. As γδ T cells participate in the inflammatory process of COVID-19, we have investigated the therapeutical potential of statins as a tool to inhibit γδ T cell pro-inflammatory activities; (2) Methods: we harvested peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with mild clinical manifestatio…
Supplemental Material - Autologous conditioned serum for chronic pain in patients with osteoarthritis: A feasibility observational study
Supplemental Material for Autologous conditioned serum for chronic pain in patients with osteoarthritis: A feasibility observational study by Mariachiara Ippolito, Giulia Spurio, Viviana Compagno, Alessandra Rizzo, Marta Di Simone, Anna Maria Corsale, Giuseppina Mazzola, Antonino Giarratano, Serena Meraviglia, Andrea Cortegiani, and Antonietta Alongi in British Journal of Pain
Where could gammadelta T cells take us in the treatment of cancer?
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Metabolic Changes in Tumor Microenvironment: How Could They Affect γδ T Cells Functions?
The metabolic changes that occur in tumor microenvironment (TME) can influence not only the biological activity of tumor cells, which become more aggressive and auto sustained, but also the immune response against tumor cells, either producing ineffective responses or polarizing the response toward protumor activity. γδ T cells are a subset of T cells characterized by a plasticity that confers them the ability to differentiate towards different cell subsets according to the microenvironment conditions. On this basis, we here review the more recent studies focused on altered tumor metabolism and γδ T cells, considering their already known antitumor role and the possibility of manipulating th…
Autologous conditioned serum for chronic pain in patients with osteoarthritis: A feasibility observational study
Background Autologous conditioned serum is a product of blood origin, with fragmented evidence of therapeutic properties in osteoarthritis chronic pain. This pilot observational prospective study aimed to evaluate the feasibility of a treatment with conditional autologous serum (ACS) in patients with severe chronic pain and grade I-III osteoarthritis and to describe its cytokine content. Methods We prospectively collected data on consecutive patients affected by osteoarthritis grade I to III and treated with four weekly injections of ACS at our outpatient pain service. The primary outcome was pain intensity, measured with the visual analogic scale (VAS). Additional outcomes were symptoms ev…
Analysis of colon-infiltrating γδ T cells in chronic inflammatory bowel disease and in colitis-associated cancer
Abstract Inflammatory bowel disease (IBD) remains a global health problem with a significant percentage of patients progressing to chronic inflammation and colitis-associated cancer (CAC). Whether or not γδ T cells contribute to initiation and maintenance of inflammation in IBD and in the development of CAC is not known. We have evaluated the frequency, phenotype, and functions of γδ T cells among tissue-infiltrating lymphocytes in healthy donors and IBD and CAC patients. Results show that Vδ1 T cells are the dominant γδ T-cell population in healthy tissue, whereas Vδ2 T significantly abound in chronic IBD. Vδ2 T cells produce more IFN-γ, TNF-α, and IL-17 than Vδ1 T cells in chronic inflame…
Anti-inflammatory properties of lemon-derived extracellular vesicles are achieved through the inhibition of ERK/NF-κB signalling pathways
Chronic inflammation is associated with the occurrence of several diseases. However, the side effects of anti-inflammatory drugs prompt the identification of new therapeutic strategies. Plant-derived extracellular vesicles (PDEVs) are gaining increasing interest in the scientific community for their biological properties. We isolated PDEVs from the juice of Citrus limon L. (LEVs) and characterized their flavonoid, limonoid and lipid contents through reversed-phase high-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (RP-HPLC-ESI-Q-TOF-MS). To investigate whether LEVs have a protective role on the inflammatory process, murine a…
Sicilian semi- and supercentenarians: identification of age-related T cell immunophenotype to define longevity trait
: The immunophenotype of oldest centenarians, i.e., semi- and supercentenarians, could provide important information about their ability to adapt to factors associated with immune changes, including ageing per se and chronic Cytomegalovirus infection. We investigated, by flow cytometry, variations in percentages and absolute numbers of immune cell subsets, focusing on T cells, and pro-inflammatory parameters in a cohort of 28 women and 26 men (age range 19-110 years). We observed variability in hallmarks of immunosenescence related to age and Cytomegalovirus serological status. The eight oldest centenarians showed the lowest percentages of naïve T cells, due to their age, and the highest pe…