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Abstract: Electrical signals have been implied in many biological mechanisms, including wound healing, which has been associated with transient electrical currents not present in intact skin. One method to generate electrical signals similar to those naturally occurring in wounds is by supplementation of galvanic particles dispersed in a cream or gel. We constructed a three-layered model of skin consisting of human dermal fibroblasts in hydrogel (mimic of dermis), a hydrogel barrier layer (mimic of epidermis) and galvanic microparticles in hydrogel (mimic of a cream containing galvanic particles applied to skin). Using this model, we investigated the effects of the properties and amounts of Cu/Zn galvanic particles on adult human dermal fibroblasts in terms of the speed of wound closing and gene expression. The collected data suggest that the effects on wound closing are due to the ROS-mediated enhancement of fibroblast migration, which is in turn mediated by the BMP/SMAD signaling pathway. These results imply that topical low-grade electric currents via microparticles could enhance wound healing. [Copyright &y& Elsevier]

Highlights: [•] Functional human tissues can be grown using cells, scaffolds and bioreactors. [•] In vitro and in vivo, cells interact with their entire environment. [•] Designs of biomimetic systems are guided by biological principles. [•] Microphysiological platforms allow preclinical testing of drugs. [•] We discuss the design of engineered microtissues for drug screening. [ABSTRACT FROM AUTHOR]

Introduction: The heart is one of the least regenerative organs in the body and any major insult can result in a significant loss of heart cells. The development of an in vitro-based cardiac tissue could be of paramount importance for many aspects of the cardiology research. In this context, we developed an in vitro assay based on human cardiomyocytes (hCMs) and ad hoc micro-technologies, suitable for several applications: from pharmacological analysis to physio-phatological studies on transplantable hCMs. We focused on the development of an assay able to analyze not only hCMs viability, but also their functionality. Methods: hCMs were cultured onto a poly-acrylamide hydrogel with tunable tissue-like mechanical properties and organized through micropatterning in a 20620 array. Arrayed hCMs were characterized by immunofluorescence, GAP-FRAP analyses and live and dead assay. Their functionality was evaluated monitoring the excitation-contraction coupling. Results: Micropatterned hCMs maintained the expression of the major cardiac markers (cTnT, cTnI, Cx43, Nkx2.5, α-actinin) and functional properties. The spontaneous contraction frequency was (0.83±0.2) Hz, while exogenous electrical stimulation lead to an increase up to 2 Hz. As proof of concept that our device can be used for screening the effects of pathological conditions, hCMs were exposed to increasing levels of H2O2. Remarkably, hCMs viability was not compromised with exposure to 0.1 mM H2O2, but hCMs contractility was dramatically suppressed. As proof of concept, we also developed a microfluidic platform to selectively treat areas of the cell array, in the perspective of performing multi-parametric assay. Conclusions: Such system could be a useful tool for testing the effects of multiple conditions on an in vitro cell model representative of human heart physiology, thus potentially helping the processes of therapy and drug development. [ABSTRACT FROM AUTHOR]

Abstract: In the past few decades the scientific community has been recognizing the paramount role of the cell microenvironment in determining cell behavior. In parallel, the study of human stem cells for their potential therapeutic applications has been progressing constantly. The use of advanced technologies, enabling one to mimic the in vivo stem cell microenviroment and to study stem cell physiology and physio-pathology, in settings that better predict human cell biology, is becoming the object of much research effort. In this review we will detail the most relevant and recent advances in the field of biosensors and micro- and nano-technologies in general, highlighting advantages and disadvantages. Particular attention will be devoted to those applications employing stem cells as a sensing element. [ABSTRACT FROM AUTHOR]

Abstract: We discuss the utilization of micro-bioreactor arrays for controlling cellular environments in studies of factors that regulate the differentiation of human embryonic stem cells. To this end, we have designed a simple and practical system that couples a microfluidic platform with an array of micro-bioreactors, and has the size of a microscope slide [E. Figallo, C. Cannizzaro, S. Gerecht, J.A. Burdick, R. Langer, N. Elvassore, G. Vunjak-Novakovic, Lab Chip 7 (2007) 710–719]. The system allows quantitative studies of cells cultured in monolayers or encapsulated in three-dimensional hydrogels. We review the operating requirements for studies of human embryonic stem cells (hESCs) under steady-state and dynamic conditions, and the related control of the mass transport and hydrodynamic shear. We describe the design and fabrication of the individual bioreactor components, and the criteria for selecting the bioreactor configuration and operating parameters, based on the analysis of the characteristic times and scales of reaction, convection and diffusion. To illustrate the utility of the bioreactor, we present a “case study” of hESC cultivation with detailed experimental methods and representative biological readouts. [Copyright &y& Elsevier]

The zebrafish (Danio rerio) is a valuable model organism for studying human biology due to its easy genetic manipulation and small size. It is optically transparent and shares genetic similarities with humans, making it ideal for studying developmental processes, diseases, and drug screening via imaging-based approaches. Solid malignant tumors often contain hypoxic areas that stimulate the release of extracellular vesicles (EVs), lipid-bound structures released by cells into the extracellular space, that facilitate short- and long-range intercellular communication and metastatization. Here we investigate the effects of EVs derived from neuroblastoma (NB), a pediatric solid tumor, on metastatic niche formation using the zebrafish as an in vivo model. Intravascular injection in zebrafish embryos allows a non-invasive visualization of EVs dispersion, uptake, and interactions with host cells. To improve repeatability of our results and ease the injection steps, we used an agarose device replica molded from a custom designed micromilled aluminum mold. We first demonstrated that EVs released under hypoxic conditions promote angiogenesis and are more easily internalized by endothelial cells than those purified from normoxic cells. We also showed that injection of with hypoxic EVs increased macrophages mobilization. We then focused on the caudal hematopoietic tissue (CHT) region of the embryo as a potential metastatic site. After hypoxic EVs injection, we highlighted changes in the expression of mmp-9 and cxcl8b genes. Furthermore, we investigated the ability of NB-derived EVs to prime a metastatic niche by a two-step injection of EVs first, followed by NB cells. Interestingly, we found that embryos injected with hypoxic EVs had more proliferating NB cells than those injected with normoxic EVs. Our findings suggest that EVs released by hypoxic NB cells alter the behavior of recipient cells in the zebrafish embryo and promote metastatic outgrowth. In addition, we demonstrated the ability of the zebrafish embryo to be a suitable model for studying the interactions between EVs and recipient cells in the metastatic process. [ABSTRACT FROM AUTHOR]

Wearable technologies are attracting increasing attention in the materials science field, prompting a quest for active components with beneficial functional attributes whilst ensuring human and environmental safety. Hydrogels are highly biocompatible platforms with interesting mechanical properties, which can be exploited for the construction of strain sensors. In order to improve the directionality of their strain response and combine it with electrical properties to fabricate piezoresistive devices, it is possible to incorporate various types of nanofillers within the polymeric network of the hydrogels. 2D materials are ideal nanofillers thanks to their intrinsic two‐dimensional anisotropy and unique electronic properties. Herein, the covalent functionalization of 2D 1T‐MoS2 is exploited to build robust hybrid cross‐linked networks with a polyethylene glycol diacrylate gel (PEGDA). The conductivity of this nanocomposite is also further improved by inducing the interfacial polymerization of aniline. The resulting free‐standing samples demonstrate a linear and highly reversible piezoresistive response in a pressure range compatible with that of peripheral blood, while also featuring good compatibility with human skin cells, thereby making them interesting options for incorporation into wearable strain sensors. [ABSTRACT FROM AUTHOR]

Human-induced pluripotent stem cells (hiPSCs) are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs) recapitulate phenotypic differences caused by genetic variations, making them attractive human disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as sources of cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs; the methods used to improve scalability of throughput assays for functional screening and drug testing in vitro; the phenotypic characteristics of hiPSCs-derived CMs and their ability to rescue injured CMs through paracrine effects; we also cover the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their immunological features and the potential use in biomedical applications. [ABSTRACT FROM AUTHOR]

Diffuse intrinsic pontine glioma (DIPG), affecting children aged 4–7 years, is a rare, aggressive tumor that originates in the pons and then spreads to nearby tissue. DIPG is the leading cause of death for pediatric brain tumors due to its infiltrative nature and inoperability. Radiotherapy has only a palliative effect on stabilizing symptoms. In silico and preclinical studies identified ONC201 as a cytotoxic agent against some human cancer cell lines, including DIPG ones. A single-crystal X-ray analysis of the complex of the human mitochondrial caseinolytic serine protease type C (hClpP) and ONC201 (PDB ID: 6DL7) allowed hClpP to be identified as its main target. The hyperactivation of hClpP causes damage to mitochondrial oxidative phosphorylation and cell death. In some DIPG patients receiving ONC201, an acquired resistance was observed. In this context, a wide program was initiated to discover original scaffolds for new hClpP activators to treat ONC201-non-responding patients. Harmaline, a small molecule belonging to the chemical class of β-carboline, was identified through Fingerprints for Ligands and Proteins (FLAP), a structure-based virtual screening approach. Molecular dynamics simulations and a deep in vitro investigation showed interesting information on the interaction and activation of hClpP by harmaline. [ABSTRACT FROM AUTHOR]

Current investigations in the field of toxicology mostly rely on 2D cell cultures and animal models. Although well-accepted, the traditional 2D cell-culture approach has evident drawbacks and is distant from the in vivo microenvironment. To overcome these limitations, increasing efforts have been made in the development of alternative models that can better recapitulate the in vivo architecture of tissues and organs. Even though the use of 3D cultures is gaining popularity, there are still open questions on their robustness and standardization. In this review, we discuss the current spheroid culture and organ-on-a-chip techniques as well as the main conceptual and technical considerations for the correct establishment of such models. For each system, the toxicological functional assays are then discussed, highlighting their major advantages, disadvantages, and limitations. Finally, a focus on the applications of 3D cell culture for mycotoxin toxicity assessments is provided. Given the known difficulties in defining the safety ranges of exposure for regulatory agency policies, we are confident that the application of alternative methods may greatly improve the overall risk assessment. [ABSTRACT FROM AUTHOR]

Advanced cell culture systems creating a controlled and predictable microenvironment together with computational modeling may be useful tools to optimize the efficiency of cell infections. In this paper, we will present a phenomenological study of a virus-host infection system, and the development of a multilayered microfluidic platform used to accurately tune the virus delivery from a diffusive-limited regime to a convective-dominated regime. Mathematical models predicted the convective-diffusive regimes developed within the system itself and determined the dominating mass transport phenomena. Adenoviral vectors carrying the enhanced green fluorescent protein (EGFP) transgene were used at different multiplicities of infection (MOI) to infect multiple cell types, both in standard static and in perfused conditions. Our results validate the mathematical models and demonstrate how the infection processes through perfusion via microfluidic platform led to an enhancement of adenoviral infection efficiency even at low MOIs. This was particularly evident at the longer time points, since the establishment of steady-state condition guaranteed a constant viral concentration close to cells, thus strengthening the efficiency of infection. Finally, we introduced the concept of effective MOI, a more appropriate variable for microfluidic infections that considers the number of adenoviruses in solution per cell at a certain time. [ABSTRACT FROM AUTHOR]

Background: Tumor hypoxia stimulates release of extracellular vesicles (EVs) that facilitate short- and long-range intercellular communication and metastatization. Albeit hypoxia and EVs release are known features of Neuroblastoma (NB), a metastasis-prone childhood malignancy of the sympathetic nervous system, whether hypoxic EVs can facilitate NB dissemination is unclear. Methods: Here we isolated and characterized EVs from normoxic and hypoxic NB cell culture supernatants and performed microRNA (miRNA) cargo analysis to identify key mediators of EVs biological effects. We then validated if EVs promote pro-metastatic features both in vitro and in an in vivo zebrafish model. Results: EVs from NB cells cultured at different oxygen tensions did not differ for type and abundance of surface markers nor for biophysical properties. However, EVs derived from hypoxic NB cells (hEVs) were more potent than their normoxic counterpart in inducing NB cells migration and colony formation. miR-210-3p was the most abundant miRNA in the cargo of hEVs; mechanistically, overexpression of miR-210-3p in normoxic EVs conferred them pro-metastatic features, whereas miR-210-3p silencing suppressed the metastatic ability of hypoxic EVs both in vitro and in vivo. Conclusion: Our data identify a role for hypoxic EVs and their miR-210-3p cargo enrichment in the cellular and microenvironmental changes favoring NB dissemination. [ABSTRACT FROM AUTHOR]

The article titled "Hybrid Piezoresistive 2D MoS2/PEGDA/PANI Covalent Hydrogels for the Sensing of Low-to-Medium Pressure" by Teresa Gatti and co-workers discusses a new type of pressure sensor. The sensor is made of a hybrid hydrogel containing 2D MoS2 wrapped by polyaniline chains. When small external pressures are applied to the hydrogel, it creates conductive pathways for electrical current to flow through the network. This research has potential applications in various fields. [Extracted from the article]

Humans are exposed to complex mixtures of mycotoxins through diet. Despite the serious threat they pose, mycotoxin risk assessment often overlooks co-exposure. With the aim of filling this gap, the present study investigates the combined cytotoxicity of sterigmatocystin (STE), ochratoxin A (OTA) and patulin (PAT) in human tumour Neuroblastoma and healthy Mesenchymal Stem Cells three-dimensional (3D) spheroids. The range of concentrations tested (1.56–50 μM for STE, 0.78–25 μM for OTA and 0.15–5 μM for PAT) was selected considering the IC 50 values obtained in previous studies and the estimated dietary exposure of consumers. To ensure appropriate experimental conditions, assessments for single mycotoxins and their combinations were conducted simultaneously. The nature of the toxicological interactions among the mycotoxins was then defined using the isobologram analysis. Our results demonstrated increased cytotoxicity in mycotoxin mixtures compared to individual exposure, with abundance of synergistic interactions. These findings highlight that the co-occurrence of STE, OTA and PAT in food may increase their individual toxic effects and should not be underestimated. Moreover, the use of advanced culture models increased the reliability and physiological relevance of our results which can serve as a groundwork for formulating standardized regulatory approaches towards mycotoxin mixtures in food and feed. • To assess the cytotoxicity associated with the co-exposure to STE, OTA and PAT. • To facilitate a deeper understanding, advanced culture models (spheroids) were used. • The nature of toxicological interactions was defined by isobologram analysis. • In BM-MSCs spheroids, single mycotoxin effects were enhanced by combined exposure. • In SH-SY5Y spheroids, mainly additive/synergistic interactions were revealed. [ABSTRACT FROM AUTHOR]

The classification of high dimensional gene expression data is key to the development of effective diagnostic and prognostic tools. Feature selection involves finding the best subset with the highest power in predicting class labels. Here, we conducted a comparative study focused on different combinations of feature selectors (Chi-Squared, mRMR, Relief-F, and Genetic Algorithms) and classification learning algorithms (Random Forests, PLS-DA, SVM, Regularized Logistic/Multinomial Regression, and kNN) to identify those with the best predictive capacity. The performance of each combination is evaluated through an empirical study on three benchmark cancer-related microarray datasets. Our results first suggest that the quality of the data relevant to the target classes is key for the successful classification of cancer phenotypes. We also proved that, for a given classification learning algorithm and dataset, all filters have a similar performance. Interestingly, filters achieve comparable or even better results with respect to the GA-based wrappers, while also being easier and faster to implement. Taken together, our findings suggest that simple, well-established feature selectors in combination with optimized classifiers guarantee good performances, with no need for complicated and computationally demanding methodologies. [ABSTRACT FROM AUTHOR]

Abstract: Stem cells hold promise to revolutionize modern medicine by the development of new therapies, disease models and drug screening systems. Standard cell culture systems have limited biological relevance because they do not recapitulate the complex 3-dimensional interactions and biophysical cues that characterize the in vivo environment. In this review, we discuss the current advances in engineering stem cell environments using novel biomaterials and bioreactor technologies. We also reflect on the challenges the field is currently facing with regard to the translation of stem cell based therapies into the clinic. [Copyright &y& Elsevier]

The New York Stem Cell Foundation's 'Fifth Annual Translational Stem Cell Research Conference' convened on October 12-13, 2010 at the Rockefeller University in New York City. The conference attracted over 400 scientists, patient advocates, and stem cell research supporters from 16 countries. In addition to poster and platform presentations, the conference featured panels entitled 'Road to the Clinic' and 'Regulatory Roadblocks.' [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 epidemic highlights the need for effective tools capable of predicting the onset of infection outbreaks at their early stages. The tracing of confirmed cases and the prediction of the local dynamics of contagion through early indicators are crucial measures to a successful fight against emerging infectious diseases (EID). The proposed framework is model-free and applies Early Warning Detection Systems (EWDS) techniques to detect changes in the territorial spread of infections in the very early stages of onset. This study uses publicly available raw data on the spread of SARS-CoV-2 mainly sourced from the database of the Italian Civil Protection Department. Two distinct EWDS approaches, the Hub-Jones (H&J) and Strozzi-Zaldivar (S&Z), are adapted and applied to the current SARS-CoV-2 outbreak. They promptly generate warning signals and detect the onset of an epidemic at early surveillance stages even if working on the limited daily available, open-source data. Additionally, EWDS S&Z criterion is theoretically validated on the basis of the epidemiological SIR. Discussed EWDS successfully analyze self-accelerating systems, like the SARS-CoV-2 scenario, to precociously identify an epidemic spread through the calculation of onset parameters. This approach can also facilitate early clustering detection, further supporting common fight strategies against the spread of EIDs. Overall, we are presenting an effective tool based on solid scientific and methodological foundations to be used to complement medical actions to contrast the spread of infections such as COVID-19. [ABSTRACT FROM AUTHOR]

Micropatterning techniques and substrate engineeringare becominguseful tools to investigate several aspects of cell–cell interactionbiology. In this work, we rationally study how different micropatterninggeometries can affect myoblast behavior in the early stage of in vitromyogenesis. Soft hydrogels with physiological elasticmodulus (E= 15 kPa) were micropatterned in parallellanes (100, 300, and 500 μm width) resulting in different localand global myoblast densities. Proliferation and differentiation intomultinucleated myotubes were evaluated for murine and human myoblasts.Wider lanes showed a decrease in murine myoblast proliferation: (69± 8)% in 100 μm wide lanes compared to (39 ± 7)% in500 μm lanes. Conversely, fusion index increased in wider lanes:from (46 ± 7)% to (66 ± 7)% for murine myoblasts, and from(15 ± 3)% to (36 ± 2)% for human primary myoblasts, usinga patterning width of 100 and 500 μm, respectively. These resultsare consistent with both computational modeling data and conditionedmedium experiments, which demonstrated that wider lanes favor theaccumulation of endogenous secreted factors. Interestingly, humanprimary myoblast proliferation is not affected by patterning width,which may be because the high serum content of their culture mediumoverrides the effect of secreted factors. These data highlight therole of micropatterning in shaping the cellular niche through secretedfactor accumulation, and are of paramount importance in rationallyunderstanding myogenesis in vitrofor the correctdesign of in vitroskeletal muscle models. [ABSTRACT FROM AUTHOR]

[Display omitted] • Current models of cancer result in low yield and high cost of drug testing. • Cancer metastasis is of greatest interest and most difficult to model. • New models provide patient-specific studies of cancer progression and treatment. • The model complexity can be tailored to capture the specific aspects of cancer. • We propose a framework for selecting and designing an appropriate model. Major progress in the understanding and treatment of cancer have tremendously improved our knowledge of this complex disease and improved the length and quality of patients' lives. Still, major challenges remain, in particular with respect to cancer metastasis which still escapes effective treatment and remains responsible for 90% of cancer related deaths. In recent years, the advances in cancer cell biology, oncology and tissue engineering converged into the engineered human tissue models of cancer that are increasingly recapitulating many aspects of cancer progression and response to drugs, in a patient-specific context. The complexity and biological fidelity of these models, as well as the specific questions they aim to investigate, vary in a very broad range. When selecting and designing these experimental models, the fundamental question is "how simple is complex enough" to accomplish a specific goal of cancer research. Here we review the state of the art in developing and using the human tissue models in cancer research and developmental drug screening. We describe the main classes of models providing different levels of biological fidelity and complexity, discuss their advantages and limitations, and propose a framework for designing an appropriate model for a given study. We close by outlining some of the current needs, opportunities and challenges in this rapidly evolving field. [ABSTRACT FROM AUTHOR]

This work proposes a comprehensive approach to optimize the design of microfluidic concentration gradient generators (MGGs) for biomedical applications. Exposing biological systems to controlled gradients enables fast screenings of induced concentration-dependent signals and surpasses several limitations of conventional cell culture techniques. The MGG working principle is the formation of diffusion-driven concentration gradients between a source and a sink, both connected to a cell culture chamber through an array of microchannels. The devices were modeled with Comsol Multiphysics®, in a combined fluid-dynamic and mass-transport study allowing prediction of the internal fields and guiding design optimization. Ideal MGGs must ensure fast transients (< 1 h) to reach a steady gradient. To identify the key features determining the device performance, we analyzed design specifications and operating parameters including: the shape of the source and sink (width 1–2 mm), the number and length of the microchannels (17–34, and 2.5–5 mm), the flow rate (5–10 μl/min). Our results prove that the formation and shape of the gradient are strongly affected by the device geometry, and mostly by the microchannels length. In addition, higher flow rates lead to the generation of stagnation zones and increase the gradient steepness. The model optimized MGG was fabricated and proved successful in the generation of stable concentration gradients over cell monolayers inside the culture chamber. [Display omitted] • Microfluidic-driven concentration gradients are fundamental for biomedical research. • Computational modeling guides the design optimization of microfluidic devices. • The provided sizing and manufacturing guidelines aid parameters selections for the desired performance-based device. • A case-study microfluidic gradient generator was simulated, fabricated, and validated. [ABSTRACT FROM AUTHOR]

Given the increasing importance of establishing better risk assessments for mycotoxins, novel in vitro tools for the evaluation of their toxicity are mandatory. In this study, an in vitro 3D spheroid model from SH-SY5Y cells, a human neuroblastoma cell line, was developed, optimized and characterized to test the cytotoxic effects caused by the mycotoxin sterigmatocystin (STE). STE induced a concentration- and time-dependent cell viability decrease in spheroids. Spheroids displayed cell disaggregation after STE exposure, increasing in a dose-dependent manner and over time. STE also induced apoptosis as confirmed by immunofluorescence staining and Western blot. Following the decreased proliferation and increased apoptosis, STE cytostasis effects were observed by migration assays both in 2D and 3D cell culture. Increased ROS generation, as well as DNA damage were also observed. Taken together, these data highlight the cytotoxic properties of STE and suggest that cell culture models play a pivotal role in the toxicological risk assessment of mycotoxins. The evaluation of cytotoxicity in spheroids (3D) rather than monolayer cultures (2D) is expected to more accurately reflect in vivo -like cell behaviour. • Sterigmatocystin (STE) toxicity was evaluated in spheroids of neuroblastoma cells. • STE induced higher mortality in SH-SY5Y spheroids than SK-N-DZ spheroids. • STE induced oxidative stress, apoptosis and DNA damage in 3D SH-SY5Y cells. • Cytostasis effects were mainly observed in 2D and 3D SH-SY5Y cells exposed to STE. • Results obtained in spheroids provided a more realistic portrait of STE toxicity. [ABSTRACT FROM AUTHOR]

Neuroblastoma is an embryonal malignancy of early childhood arising from the embryonic sympatho-adrenal lineage of the neural crest. About half of all cases are currently classified as high-risk of disease recurrence, with an overall survival rate of less than 40% at 5 years despite intensive therapy. Recent studies on matched primary tumours and at the relapse revealed downregulation of genes transcriptionally silenced by YAP as significant association with neuroblastoma relapse. Here, we evaluated the pharmacological targeting of YAP/TAZ with the YAP/TAZ-TEAD inhibitor Verteporfin (VP) in Tumour Initiating Cells (TICs) derived from High-Risk Neuroblastoma patients. VP treatment suppresses YAP/TAZ expression, induces apoptosis and causes the re-organization of the cytoskeleton reducing cells migration and clonogenic ability. Moreover, VP reduces the percentage of side population cells and ABC transporters involved in drug resistance, and the percentage of stem cell subpopulations CD133+ and CD44+ of TICs. Finally, we demonstrated that VP sensitizes TICs to the standard drugs used for neuroblastoma therapy etoposide and cis-platin opening the way to use VP as drug repositioning candidate for recurrent neuroblastoma. • Verteporfin, a specific YAP/TAZ-TEAD complex inhibitor, inhibits NB-TIC cell growth. • Cell migration and invasion were reduced in metastatic NB-TIC cells. • Verteporfin reduces side population and cancer stem cell properties of NB-TICs. • Verteporfin sensitizes NB-TIC to the chemotherapeutic drugs etoposide and cisplatin. [ABSTRACT FROM AUTHOR]