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Publications

2024

  • Davide Raineri, Hugo Abreu, Beatrice Vilardo, Natasa Kustrimovic, Chiara Venegoni, Giuseppe Cappellano, and Annalisa Chiocchetti. Deep Flow Cytometry Unveils Distinct Immune Cell Subsets in Inducible T Cell Co-Stimulator Ligand (ICOSL)- and ICOS-Knockout Mice during Experimental Autoimmune Encephalomyelitis
    Int J Mol Sci. 2024 Mar; 25(5): 2509. doi: doi.org/10.3390/ijms25052509

    The study investigates the role of the ICOS/ICOSL system  multiple sclerosis (MS) in its animal model , i.e. experimental autoimmune encephalomyelitis (EAE). Researchers used mice lacking ICOS or ICOSL (namely knock out), key molecules in immune response regulation, to study their impact on EAE progression. Both types of knockout mice developed more severe EAE and showed a reduction in  memory/regulatory T cells responses and IL-17 levels compared to normal mice, having both ICOS and ICOSL molecules. Unique immune changes were observed in ICOSL-deficient mice, suggesting other binding partners to ICOSL may influence EAE. This highlights the need for further research into the ICOS/ICOSL pathway’s role in other  autoimmune conditions.
  • Stolfi F, Abreu H, Sinella R, Nembrini S, Centonze S, Landra V, Brasso C, Cappellano G, Rocca P and Chiocchetti A
    Omics approaches open new horizons in major depressive disorder: from biomarkers to precision medicine.
    Front. Psychiatry 15:1422939. doi: doi.org/10.3389/fpsyt.2024.1422939

    Major depressive disorder (MDD) is a recurrent episodic mood disorder that represents the third leading cause of disability worldwide. In MDD, several factors can simultaneously contribute to its development, which complicates its diagnosis. According to practical guidelines, antidepressants are the first-line treatment for moderate to severe major depressive episodes. Traditional treatment strategies often follow a one-size-fits-all approach, resulting in suboptimal outcomes for many patients who fail to experience a response or recovery and develop the so-called “therapy-resistant depression”. The high biological and clinical inter-variability within patients and the lack of robust biomarkers hinder the finding of specific therapeutic targets, contributing to the high treatment failure rates. In this frame, precision medicine, a paradigm that tailors medical interventions to individual characteristics, would help allocate the most adequate and effective treatment for each patient while minimizing its side effects. In particular, multi-omic studies may unveil the intricate interplays between genetic predispositions and exposure to environmental factors through the study of epigenomics, transcriptomics, proteomics, metabolomics, gut microbiomics, and immunomics.
  • Mazzucca CB, Scotti L, Raineri D, Cappellano G, Chiocchetti A.
    Design and Validation of MEDOC, a Tool to Assess the Combined Adherence to Mediterranean and Western Dietary Patterns.
    Nutrients. 2024; 16(11):1745. doi.org/10.3390/nu16111745

    The Mediterranean diet (MD) and Western diet (WD) are poles apart as dietary patterns. Despite the availability of epidemiological tools to estimate the adherence to MD, to date, there is a lack of combined scores. We developed MEDOC, a food frequency questionnaire (FFQ) designed to calculate a combined adherence score for both diets and validated it on 213 subjects.
  • Barbero Mazzucca C, Scotti L, Comi C, Vecchio D, Chiocchetti A, Cappellano G.
    The Role of Diet in Multiple Sclerosis Onset: A Prospective Study Using UK Biobank.
    Nutrients. 2024; 16(11):1746. doi.org/10.3390/nu16111746

    Multiple sclerosis (MS) is a debilitating autoimmune condition primarily affecting young adults, and its rise is evident globally. Despite this, its precise etiology remains elusive. Both genetic and environmental factors contribute to MS susceptibility; however, the link between diet and MS lacks substantial evidence due to limited large-scale studies. We exploited the UK Biobank resources to explore the nexus between diet, lifestyle, and MS risk. The dietary and lifestyle habits of MS incident cases, derived from a general food frequency questionnaire (FFQ) completed by all participants at study enrollment, were compared to those of subjects who did not develop MS during the follow-up.
  • Abreu H, Lallukka M, Miola M, Spriano S, Vernè E, Raineri D, Leigheb M, Ronga M, Cappellano G, Chiocchetti A.
    Human T-Cell Responses to Metallic Ion-Doped Bioactive Glasses.
    International Journal of Molecular Sciences. 2024; 25(8):4501. doi.org/10.3390/ijms25084501

    Biomaterials are extensively used as replacements for damaged tissue with bioactive glasses standing out as bone substitutes for their intrinsic osteogenic properties. However, biomaterial implantation has the following risks: the development of implant-associated infections and adverse immune responses. Thus, incorporating metallic ions with known antimicrobial properties can prevent infection, but should also modulate the immune response. Therefore, we selected silver, copper and tellurium as doping for bioactive glasses and evaluated the immunophenotype and cytokine profile of human T-cells cultured on top of these discs.

2023

  • Raineri D, Venegoni C, Calella MG, Vaschetto R, Scotti L, Canciani E, Manfredi M, Gavelli F, Castello L, Chiocchetti A, Cappellano G.
    Worse Disease Prognosis Is Associated to an Increase of Platelet-Derived Extracellular Vesicles in Hospitalized SARS-CoV-2 Patients.
    Dis Markers. 2022 Jul 7;2022:8074655. doi: doi.org/10.1155/2022/8074655. eCollection 2022.

    Platelet-derived extracellular vesicles (PLT-EVs) were found increased in our previous study on COVID-19 patients, proposing them as a potential biomarker for the infection. This research investigates the predictive value of PLT-EV levels at hospital admission and within the first week of hospitalization. We confirmed in the third-wave of COVID-19 that PLT-EV are a biomarkers of disease. Interestingly, increased PLT-EV levels were found in hospitalized patients during the first week with unfavorable outcomes, by suggesting a correlation between rising PLT-EV levels in the first week after admission and a more severe disease progression.
  • Morello G, De Iaco G, Gigli G, Polini A, Gervaso F.
    Chitosan and Pectin Hydrogels for Tissue Engineering and In Vitro Modeling.
    Gels. 2023 Feb 4;9(2):132. doi: doi.org/10.3390/gels9020132.

    Hydrogels, as biomaterials, serve as supportive scaffolds for cell organization in 3D systems, recreating physiological and pathological cellular microenvironments. They are crucial for tissue engineering and 3D in vitro models, mimicking the extracellular matrix of specific organs. Polysaccharide-based hydrogels, especially those using chitosan and pectin, demonstrate excellent biocompatibility and beneficial interaction with cellular components. Despite the growing interest in such hydrogels, there is a lack of focus on the combined use of chitosan and pectin. This review explores the biomedical applications of hydrogels incorporating both polysaccharides in tissue engineering and 3D in vitro modeling.
  • Giuliana Grasso, Francesco Colella, Stefania Forciniti, Valentina Onesto, Helena Iuele, Anna Chiara Siciliano, Federica Carnevali, Anil Chandra, Giuseppe Gigliab and Loretta L. del Mercato.
    Fluorescent nano- and microparticles for sensing cellular microenvironment: past, present and future applications,
    Nanoscale Adv., 2023, 5, 4311 , DOI: 10.1039/d3na00218g

    The tumor microenvironment (TME) holds critical markers for early cancer detection and treatment. Ratiometric fluorescence sensors play a key role in monitoring TME traits like acidity, oxygen, and ions. This review explores their latest advancements, design, and applications, offering insights into TME dynamics for improved cancer research and diagnosis.
  • Nawaz, Ahmad Ahsan and Soteriou, Despina and Xu, Catherine K. and Goswami, Ruchi and Herbig, Maik and Guck, Jochen and Girardo, Salvatore.
    Image-based cell sorting using focused travelling surface acoustic waves,
    Lab Chip, 2023, 23, 2, 372-387, doi: https://doi.org/10.1039/D2LC00636G

    The combination of real-time deformability cytometry (RT-DC) with a focused traveling surface acoustic wave (FTSAW)-based actuator provides a user-friendly, label-free, reliable, and high-throughput microfluidic device for continuous image-based cell sorting with high purity and sensitivity. In our paper recently published on Lab on a Chip Journal, we demonstrated the sorting of multiple cell types of different sizes and mechanical properties, corresponding to a wide range of mammalian cells. Our technique opens the prospect of sorting cells based on their morpho-rheological phenotype that in combination with downstream analysis can provide new insights into the correlation between cell physical properties and biological functions.
  • Rizzo, Riccardo and Onesto, Valentina and Morello, Giulia and Iuele, Helena and Scalera, Francesca and Gigli, Giuseppe and Polini, Alessandro and Gervaso, Francesca and del Mercato, Loretta L.,
    Ph-Sensing Hydrogels for Non-Invasive Metabolism Monitoring in Tumor Spheroids.
    SSRN, doi: http://dx.doi.org/10.2139/ssrn.4364505

    Acidification of extracellular pH is a well-known feature of solid tumors, correlated to cancer initiation, progression, and resistance to therapies. Monitoring local pH variations, non-invasively, during cancer growth and in response to drug treatment becomes extremely important for understanding cancer mechanisms. Here, we describe a simple and reliable pH-sensing system based on a thermoresponsive hydrogel embedding optical pH-sensors that enable non-invasive and accurate metabolism monitoring in colorectal cancer (CRC) spheroids. These findings will be essential for the study of solid tumors in vitro and the development of personalized medicine approaches.

2022

  • Bucciarelli A, Paolelli X, De Vitis E, Selicato N, Gervaso F, Gigli G, Moroni L, Polini A.
    VAT photopolymerization 3D printing optimization of high aspect ratio structures for additive manufacturing of chips towards biomedical applications,
    Additive Manufacturing, Volume 60, Part A, 2022, doi: doi.org/10.1016/j.addma.2022.103200

    The authors applied a statistical methodology, called Design of Experiment (DoE), to better understand the process factors behind the production of organ-on-chip (OoC) platforms by Digital Light Processing (DLP). DLP is an additive manufacturing technology that allows to fabricate complex OoC architectures with high resolution and flexibility in a short time.
  • Neto E, Monteiro AC, Leite Pereira C, Simões M, Conde JP, Chu V, Sarmento B, Lamghari M.
    Micropathological Chip Modeling the Neurovascular Unit Response to Inflammatory Bone Condition.
    Adv Healthc Mater. 2022 Feb 14:e2102305. doi: 10.1002/adhm.202102305
  • Polini A, Moroni L.
    The convergence of high-tech emerging technologies into the next stage of organ-on-a-chips.
    Biomaterials and Biosystems Volume 1, March 2021, 100012. doi: 10.1016/j.bbiosy.2021.100012
  • Mazzucca CB, Scotti L, Cappellano G, Barone-Adesi F, Chiocchetti A.
    Nutrition and Rheumatoid Arthritis Onset: A Prospective Analysis Using the UK Biobank.
    Nutrients. 2022; 14(8):1554. doi: 10.3390/nu14081554
  • Raineri D, Cappellano G, Vilardo B, Maione F, Clemente N, Canciani E, Boggio E, Gigliotti CL, Monge C, Dianzani C, Boldorini R, Dianzani U, Chiocchetti A.
    Inducible T-Cell Costimulator Ligand Plays a Dual Role in Melanoma Metastasis upon Binding to Osteopontin or Inducible T-Cell Costimulator.
    Biomedicines. 2022; 10(1):51. doi: 10.3390/biomedicines10010051
  • Neto, E., Monteiro, A. C., Leite Pereira, C., Simões, M., Conde, J. P., Chu, V., … & Lamghari, M. (2022).
    Micropathological Chip Modeling the Neurovascular Unit Response to Inflammatory Bone Condition.
    Advanced Healthcare Materials, 2022, 2102305. doi: 10.1002/adhm.202102305

2021

  • Mazzucca CB, Raineri D, Cappellano G, Chiocchetti A.
    How to Tackle the Relationship between Autoimmune Diseases and Diet: Well Begun Is Half-Done.
    Nutrients. 2021; 13(11):3956. doi: 10.3390/nu13113956
  • Cappellano G, Abreu H, Casale C, Dianzani U, Chiocchetti A.
    Nano-Microparticle Platforms in Developing Next-Generation Vaccines.
    Vaccines. 2021; 9(6):606. doi: 10.3390/vaccines9060606
  • Morello G, Polini A, Scalera F, Rizzo R, Gigli G, Gervaso F.
    Preparation and Characterization of Salt-Mediated Injectable Thermosensitive Chitosan/Pectin Hydrogels for Cell Embedding and Culturing.
    Polymers. 2021; 13(16):2674. doi: 10.3390/polym13162674
  • Stanzione, A., Polini, A., La Pesa, V., Quattrini, A., Romano, A., Gigli, G., … & Gervaso, F.
    Thermosensitive chitosan-based hydrogels supporting motor neuron-like NSC-34 cell differentiation.
    Biomaterials Science, 9(22), 2021, 7492-7503. doi: 10.1039/D1BM01129D
  • Polini, A., & Moroni, L. (2021).
    The convergence of high-tech emerging technologies into the next stage of organ-on-a-chips.
    Biomaterials and Biosystems, 1, 100012. doi: 10.1016/j.bbiosy.2021.100012
  • De Vitis, E., La Pesa, V., Gervaso, F., Romano, A., Quattrini, A., Gigli, G., … & Polini, A.
    A microfabricated multi-compartment device for neuron and Schwann cell differentiation.
    Scientific reports, 2021, 11(1), 1-12. doi: 10.1038/s41598-021-86300-4