Regenerative Medicine
Cell Therapy
Extracellular Vesicles
Bone Regeneration
19
Scopus Publications
Scopus Publications
From Tumour to Bloodstream: Advancing PD-L1 Testing With Liquid Biopsies in Non-Small Cell Lung Cancer R. Leporati, V. Callegari, A. Ancora, M. Palmieri, B. Riccò, E. Cabitza, L. Trudu, K. Di Emidio, C. Chiavelli, A. Eccher, I. Mastrolia, V. Catani, S. Bettelli, G. Guaitoli, M. Dominici, F. Bertolini Cytopathology, 2026 Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape of non‐small cell lung cancer (NSCLC) without actionable genomic alterations by opening new possibilities for treatment. However, the predictive value of Programmed Death‐Ligand 1 (PD‐L1) expression assessed by immunohistochemistry (IHC) is quite modest, leaving many patients without optimal benefit from ICIs. To address this gap, liquid biopsy is gaining momentum as a promising tool to complement tissue‐based PD‐L1 assessment. Liquid biopsy, which entails the analysis of circulating tumour cells (CTCs), extracellular vesicles (EVs), circulating tumour DNA (ctDNA), and other biomarkers, offers a non‐invasive approach for tracking disease evolution and interactions with the immune system. We conducted a narrative review to explore the potential of liquid biopsy in enhancing patient selection for ICIs, its predictive and prognostic value in advanced NSCLC, and the associated technical and clinical implications. By highlighting recent advancements and ongoing research efforts, we underscore the critical role of liquid biopsy in driving precision immuno‐oncology. Establishing robust, reproducible methods for PD‐L1 assessment through liquid biopsy is essential for translating this approach into clinical practice, with the potential to overcome the limitations of tissue‐based assays and better individualise immunotherapy strategies in NSCLC.
Extracellular vesicles-derived miR-21 as a biomarker for early diagnosis and tumor activity in breast cancer subtypes Claudia Omarini, Virginia Catani, Ilenia Mastrolia, Angela Toss, Federico Banchelli, Chrystel Isca, Daniele Medici, Ornella Ponzoni, Marco Brucale, Francesco Valle, Maria Cristina Baschieri, Roberto D’Amico, Valentina Masciale, Chiara Chiavelli, Federica Caggia, Carlo Augusto Bortolotti, Federico Piacentini, Massimo Dominici Biomarker Research, 2025 Emerging evidence highlights the key role of microRNA (miR)-21 in cell-to-cell communication and tumorigenesis. However, limited knowledge exists on the levels and clinical meaning of miR-21 in extracellular vesicles (EVs) of patients with breast cancer (BC). We assessed EV-derived miR-21 levels in one hundred women: 30 with early BC (EBC), 30 with metastatic BC on treatment progression (MBC), 30 cancer survivors on follow-up (FU) and 10 healthy donors (HD) as age- and body mass index (BMI)-matched controls. EVs isolated from serum samples were characterized using nanoparticle tracking analysis, scanning electron microscopy and atomic force microscopy to detect their concentration, size, morphology and mechanical properties. The levels of miR-21 in EVs was evaluated using real time PCR and compared between groups (EBC, MBC and FU vs. HD) by calculating the fold change and ΔΔCt statistic. EVs size and concentration did not differ significantly among patient groups. In the EBC group, the clinical stage at diagnosis and tumor subtype did not influence miR-21 levels. The levels of miR-21 were higher in the MBC group than in the HD group (p = 0.029), mainly in those who were human epidermal growth factor receptor 2 (HER2)+ (p = 0.0005) and hormone receptor-positive (p = 0.036). In particular, in the HER2 + subgroup, the miR-21 levels were significantly higher in those with active BC (both EBC and MBC) than in HDs (p = 0.002). Our findings suggest that miR-21 may be a promising biomarker for diagnosis and tumor activity, mainly in HER2 + BC.
Nanoplasmonic Isosbestics Uncover Mesoscale Assembly of Gold Nanoparticles on Soft Templates Jacopo Cardellini, Ilaria De Santis, Giuseppe Emanuele Lio, Marco Brucale, Francesco Valle, Virginia Catani, Ilenia Mastrolia, Marta Calabria, Massimo Dominici, Andrea Zendrini, Annalisa Radeghieri, Lucia Paolini, Paolo Bergese, Lucrezia Caselli, Debora Berti, Costanza Montis Journal of the American Chemical Society, 2025 Assembly of plasmonic nanoparticles (NPs) generates unique optical properties through coupling of the localized surface plasmon resonance (LSPR) of individual NPs. However, precisely controlling and monitoring how mesoscale assembly dictates final optical properties remain key challenges in designing advanced plasmonic materials. Here, we introduce "nanoplasmonic isosbestics" as optical descriptors of the mesoscale organization of gold nanoparticles (AuNPs) on soft templates. Unlike isosbestic points in molecular spectroscopy, which describe chemical equilibria, our numerical simulations demonstrate that nanoplasmonic isosbestics emerge from the coexistence of individual AuNPs and AuNP clusters, where the interparticle spacing determines the isosbestic wavelength. By templating AuNP assembly onto synthetic free-standing lipid bilayers with tunable membrane rigidity, we experimentally achieve precise control over interparticle spacing and prove that it is mirrored by univocal modulation of the isosbestic wavelength. This provides a fundamental understanding of the structure-function relationship in plasmonic systems, linking, for the first time, nanoplasmonic isosbestics to interparticle spacing and equilibrium structure in plasmonic assemblies. On the analytical perspective, nanoplasmonic isosbestics provide noninvasive optical fingerprints of the templates, opening to appealing applications. As a proof of concept, we apply this approach to profile the stiffness of two extracellular vesicle (EVs) classes─mesenchymal stem cell (MSC)-derived and red blood cell-derived EVs─both recognized for their biological and translational potential.
A Novel Molecular Profile of Hormone-Sensitive Prostate Cancer Defines High Risk Patients Claudia Piombino, Cecilia Nasso, Stefania Bettelli, Samantha Manfredini, Maria Giuseppa Vitale, Stefania Pipitone, Cinzia Baldessari, Matteo Costantini, Albino Eccher, Ilenia Mastrolia, Virginia Catani, Francesca Bacchelli, Stefania Ferretti, Massimo Dominici, Roberto Sabbatini Cancer Medicine, 2025 BackgroundThe therapeutic management of metastatic hormone‐sensitive prostate cancer (mHSPC) is still based on clinical and pathological parameters due to the lack of biomarkers that may drive tailored treatment.MethodsIn this non‐randomized, single‐center, retrospective trial, we searched for a genetic signature using the NanoString nCounter PanCancer Pathways Panel on formalin‐fixed paraffin embedded prostate cancer samples belonging to 48 patients with de novo or relapsed mHSPC. Patients were divided into a high‐clinical‐risk group (n = 36) and a low‐clinical‐risk group (n = 12) according to the mean time to metastatic relapse.ResultsThe analysis of Nanostring nCounter Panel data revealed differential expression of 42 genes between high‐clinical‐risk and low‐clinical‐risk groups. All the genes except for NR4A1 and FOS were upregulated in the high‐clinical‐risk group. A general overexpression of apoptosis, PI3K and MAPK pathway‐related genes, including AKT2, was observed in the high‐clinical‐risk group.ConclusionThe differential genetic signature identified between the two study groups revealed novel biomarkers in mHSPC, additionally suggesting new therapeutic targets within the hormone sensitive phase, such as AKT2. Further prospective larger cohort studies are needed to assess the prognostic value of our findings and their exact role in prostate cancer progression.
Expression of HOXB7 in the Lung of Patients with Idiopathic Pulmonary Fibrosis: A Proof-of-Concept Study Anna Valeria Samarelli, Roberto Tonelli, Giulia Raineri, Ilenia Mastrolia, Matteo Costantini, Luca Fabbiani, Virginia Catani, Tiziana Petrachi, Giulia Bruzzi, Dario Andrisani, Filippo Gozzi, Alessandro Marchioni, Valentina Masciale, Beatrice Aramini, Valentina Ruggieri, Giulia Grisendi, Massimo Dominici, Stefania Cerri, Enrico Clini Biomedicines, 2024 Background: The molecular pathways involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) still need to be fully clarified as some are shared with lung cancer development. HOXB7, a member of the homeobox (Hox) gene family, has been found involved in various cancers. Methods: Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF, retrospectively selected from the IPF database of the University Hospital of Modena. HOXB7 expression was analyzed and compared with that of five patients with no evidence of pulmonary fibrosis as controls. Results: The semi-quantitative analysis of IHC showed that HOXB7 protein expression was higher in IPF patients compared to controls (difference between means = 6.2 ± 2.37, p = 0.0157). Further, HOXB7 expression was higher in IPF patients with a higher extent of fibrosis (50–75%)—measured with high-resolution computer tomography—compared to those with a lower extent (0–25%) (difference between means = 25.74 ± 6.72, p = 0.004). Conclusions: The expression of HOXB7 is higher in the lung of IPF patients compared to controls, and was represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF.
Chasing the Role of miRNAs in RCC: From Free-Circulating to Extracellular-Vesicle-Derived Biomarkers Ilenia Mastrolia, Virginia Catani, Marco Oltrecolli, Stefania Pipitone, Maria Giuseppa Vitale, Valentina Masciale, Chiara Chiavelli, Carlo Augusto Bortolotti, Cecilia Nasso, Giulia Grisendi, Roberto Sabbatini, Massimo Dominici Biology, 2023 Renal cell carcinoma (RCC) is the second most common cancer of the urinary system. The current therapeutic strategies are based on partial or total nephrectomy and/or targeted therapies based on immune checkpoint inhibitors to which patients are often refractory. Preventive and screening strategies do not exist and the few available biomarkers for RCC are characterized by a lack of sensitivity, outlining the need for novel noninvasive and sensitive biomarkers for early diagnosis and better disease monitoring. Blood liquid biopsy (LB) is a non- or minimally invasive procedure for a more representative view of tumor heterogeneity than a tissue biopsy, potentially allowing the real-time monitoring of cancer evolution. Growing interest is focused on the extracellular vesicles (EVs) secreted by either healthy or tumoral cells and recovered in a variety of biological matrices, blood included. EVs are involved in cell-to-cell crosstalk transferring their mRNAs, microRNAs (miRNAs), and protein content. In particular, transferred miRNAs may regulate tumorigenesis and proliferation also impacting resistance to apoptosis, thus representing potential useful biomarkers. Here, we present the latest efforts in the identification of circulating miRNAs in blood samples, focusing on the potential use of EV-derived miRNAs as RCC diagnostic and prognostic markers.
Autologous Marrow Mesenchymal Stem Cell Driving Bone Regeneration in a Rabbit Model of Femoral Head Osteonecrosis Ilenia Mastrolia, Andrea Giorgini, Alba Murgia, Pietro Loschi, Tiziana Petrachi, Valeria Rasini, Massimo Pinelli, Valentina Pinto, Francesca Lolli, Chiara Chiavelli, Giulia Grisendi, Maria Cristina Baschieri, Giorgio De Santis, Fabio Catani, Massimo Dominici, Elena Veronesi Pharmaceutics, 2022 Osteonecrosis of the femoral head (ONFH) is a progressive degenerative disease that ultimately requires a total hip replacement. Mesenchymal stromal/stem cells (MSCs), particularly the ones isolated from bone marrow (BM), could be promising tools to restore bone tissue in ONFH. Here, we established a rabbit model to mimic the pathogenic features of human ONFH and to challenge an autologous MSC-based treatment. ON has been originally induced by the synergic combination of surgery and steroid administration. Autologous BM-MSCs were then implanted in the FH, aiming to restore the damaged tissue. Histological analyses confirmed bone formation in the BM-MSC treated rabbit femurs but not in the controls. In addition, the model also allowed investigations on BM-MSCs isolated before (ON-BM-MSCs) and after (ON+BM-MSCs) ON induction to dissect the impact of ON damage on MSC behavior in an affected microenvironment, accounting for those clinical approaches foreseeing MSCs generally isolated from affected patients. BM-MSCs, isolated before and after ON induction, revealed similar growth rates, immunophenotypic profiles, and differentiation abilities regardless of the ON. Our data support the use of ON+BM-MSCs as a promising autologous therapeutic tool to treat ON, paving the way for a more consolidated use into the clinical settings.
Human Adipose Mesenchymal Stromal/Stem Cells Improve Fat Transplantation Performance Maria Serena Piccinno, Tiziana Petrachi, Marco Pignatti, Alba Murgia, Giulia Grisendi, Olivia Candini, Elisa Resca, Valentina Bergamini, Francesco Ganzerli, Alberto Portone, Ilenia Mastrolia, Chiara Chiavelli, Ilaria Castelli, Daniela Bernabei, Mara Tagliazucchi, Elisa Bonetti, Francesca Lolli, Giorgio De Santis, Massimo Dominici, Elena Veronesi Cells, 2022 The resorption rate of autologous fat transfer (AFT) is 40–60% of the implanted tissue, requiring new surgical strategies for tissue reconstruction. We previously demonstrated in a rabbit model that AFT may be empowered by adipose-derived mesenchymal stromal/stem cells (AD-MSCs), which improve graft persistence by exerting proangiogenic/anti-inflammatory effects. However, their fate after implantation requires more investigation. We report a xenograft model of adipose tissue engineering in which NOD/SCID mice underwent AFT with/without human autologous AD-MSCs and were monitored for 180 days (d). The effect of AD-MSCs on AFT grafting was also monitored by evaluating the expression of CD31 and F4/80 markers. Green fluorescent protein-positive AD-MSCs (AD-MSC-GFP) were detected in fibroblastoid cells 7 days after transplantation and in mature adipocytes at 60 days, indicating both persistence and differentiation of the implanted cells. This evidence also correlated with the persistence of a higher graft weight in AFT-AD-MSC compared to AFT alone treated mice. An observation up to 180 d revealed a lower resorption rate and reduced lipidic cyst formation in the AFT-AD-MSC group, suggesting a long-term action of AD-MSCs in support of AFT performance and an anti-inflammatory/proangiogenic activity. Together, these data indicate the protective role of adipose progenitors in autologous AFT tissue resorption.
Circulating and intracellular mirnas as prognostic and predictive factors in her2-positive early breast cancer treated with neoadjuvant chemotherapy: A review of the literature Chrystel Isca, Federico Piacentini, Ilenia Mastrolia, Valentina Masciale, Federica Caggia, Angela Toss, Claudia Piombino, Luca Moscetti, Monica Barbolini, Michela Maur, Massimo Dominici, Claudia Omarini Cancers, 2021 MicroRNAs (miRNA) are small noncoding RNAs that can act as both oncogene and tumor suppressors. Deregulated miRNA expression has been detected in human cancers, including breast cancer (BC). Considering their important roles in tumorigenesis, miRNAs have been investigated as potential prognostic and diagnostic biomarkers. Neoadjuvant setting is an optimal model to investigate in vivo the mechanism of treatment resistance. In the management of human epidermal growth factor receptor-2 (HER2)-positive early BC, the anti-HER2-targeted therapies have drastically changed the survival outcomes. Despite this, growing drug resistance due to the pressure of therapy is relatively frequent. In the present review, we focused on the main miRNAs involved in HER2-positive BC tumorigenesis and discussed the recent evidence on their predictive and prognostic value.
Dissecting the Role of Mesenchymal Stem Cells in Idiopathic Pulmonary Fibrosis: Cause or Solution Anna Valeria Samarelli, Roberto Tonelli, Irene Heijink, Aina Martin Medina, Alessandro Marchioni, Giulia Bruzzi, Ivana Castaniere, Dario Andrisani, Filippo Gozzi, Linda Manicardi, Antonio Moretti, Stefania Cerri, Riccardo Fantini, Luca Tabbì, Chiara Nani, Ilenia Mastrolia, Daniel J. Weiss, Massimo Dominici, Enrico Clini Frontiers in Pharmacology, 2021 Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of idiopathic interstitial pneumonias, characterized by chronic and progressive fibrosis subverting the lung’s architecture, pulmonary functional decline, progressive respiratory failure, and high mortality (median survival 3 years after diagnosis). Among the mechanisms associated with disease onset and progression, it has been hypothesized that IPF lungs might be affected either by a regenerative deficit of the alveolar epithelium or by a dysregulation of repair mechanisms in response to alveolar and vascular damage. This latter might be related to the progressive dysfunction and exhaustion of the resident stem cells together with a process of cellular and tissue senescence. The role of endogenous mesenchymal stromal/stem cells (MSCs) resident in the lung in the homeostasis of these mechanisms is still a matter of debate. Although endogenous MSCs may play a critical role in lung repair, they are also involved in cellular senescence and tissue ageing processes with loss of lung regenerative potential. In addition, MSCs have immunomodulatory properties and can secrete anti-fibrotic factors. Thus, MSCs obtained from other sources administered systemically or directly into the lung have been investigated for lung epithelial repair and have been explored as a potential therapy for the treatment of lung diseases including IPF. Given these multiple potential roles of MSCs, this review aims both at elucidating the role of resident lung MSCs in IPF pathogenesis and the role of administered MSCs from other sources for potential IPF therapies.
Impact of HOXB7 overexpression on human adipose-derived mesenchymal progenitors Elisabetta Manuela Foppiani, Olivia Candini, Ilenia Mastrolia, Alba Murgia, Giulia Grisendi, Anna Valeria Samarelli, Giulia Boscaini, Lucrezia Pacchioni, Massimo Pinelli, Giorgio De Santis, Edwin M. Horwitz, Elena Veronesi, Massimo Dominici Stem Cell Research and Therapy, 2019
MSC-delivered soluble TRAIl and paclitaxel as novel combinatory treatment for pancreatic adenocarcinoma Filippo Rossignoli, Carlotta Spano, Giulia Grisendi, Elisabetta Manuela Foppiani, Giulia Golinelli, Ilenia Mastrolia, Marco Bestagno, Olivia Candini, Tiziana Petrachi, Alessandra Recchia, Francesca Miselli, Giulia Rovesti, Giulia Orsi, Elena Veronesi, Gregorio Medici, Benedetta Petocchi, Massimo Pinelli, Edwin M. Horwitz, Pierfranco Conte, Massimo Dominici Theranostics, 2019
GD2 expression in breast cancer Giulia Orsi, Monica Barbolini, Guido Ficarra, Giovanni Tazzioli, Paola Manni, Tiziana Petrachi, Ilenia Mastrolia, Enrico Orvieto, Carlotta Spano, Malvina Prapa, Shaniko Kaleci, Roberto D’Amico, Valentina Guarneri, Maria Vittoria Dieci, Stefano Cascinu, Pierfranco Conte, Federico Piacentini, Massimo Dominici Oncotarget, 2017
