Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs’ self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/β-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process.

Bone marrow-derived mesenchymal stem cells (MSCs) have successfully progressed to phase III clinical trials successive to an intensive in vitro and pre-clinical assessment in experimental animal models of ischemic myocardial injury. With scanty evidence regarding their cardiogenic differentiation in the recipient patients’ hearts post-engraftment, paracrine secretion of bioactive molecules is being accepted as the most probable underlying mechanism to interpret the beneficial effects of cell therapy. Secretion of small non-coding microRNA (miR) constitutes an integral part of the paracrine activity of stem cells, and there is emerging interest in miRs’ delivery to the heart as part of cell-free therapy to exploit their integral role in various cellular processes. MSCs also release membrane vesicles of diverse sizes loaded with a wide array of miRs as part of their paracrine secretions primarily for intercellular communication and to shuttle genetic material. Exosomes can also be loaded with miRs of interest for delivery to the organs of interest including the heart, and hence, exosome-based cell-free therapy is being assessed for cell-free therapy as an alternative to cell-based therapy. This review of literature provides an update on cell-free therapy with primary focus on exosomes derived from BM-derived MSCs for myocardial repair.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) of unknown aetiology, with a median survival of 2–4 years from the time of diagnosis. Although IPF has unknown aetiology by definition, there have been identified several risks factors increasing the probability of the onset and progression of the disease in IPF patients such as cigarette smoking and environmental risk factors associated with domestic and occupational exposure. Among them, cigarette smoking together with concomitant emphysema might predispose IPF patients to lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer development. To this purpose, IPF and LC share several cellular and molecular processes driving the progression of both pathologies such as fibroblast transition proliferation and activation, endoplasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose IPF patients to LC development. Nintedanib, a tyrosine–kinase inhibitor, was firstly developed as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target molecular pathway. In this review our aim is to describe the updated studies on common cellular and molecular mechanisms between IPF and lung cancer, knowledge of which might help to find novel therapeutic targets for this disease combination.

Primary spontaneous pneumothorax (PSP) is one of the most common thoracic diseases affecting adolescents and young adults. Despite the high incidence of PSP and the availability of several international guidelines for its diagnosis and treatment, a significant behavioural heterogeneity can be found among those management recommendations. A working group of the Italian Society of Thoracic Surgery summarized the best evidence available on PSP management with the methodological tool of a systematic review assessing the quality of previously published guidelines with the Appraisal of Guidelines for Research and Evaluation (AGREE) II. Concerning PSP physiopathology, the literature seems to be equally divided between those who support the hypothesis of a direct correlation between changes in atmospheric pressure and temperature and the incidence of PSP, so it is not currently possible to confirm or reject this theory with reasonable certainty. Regarding the choice between conservative treatment and chest drainage in the first episode, there is no evidence on whether one option is superior to the other. Video-assisted thoracic surgery represents the most common and preferred surgical approach. A primary surgical approach to patients with their first PSP seems to guarantee a lower recurrence rate than that of a primary approach consisting of a chest drainage positioning; conversely, the percentage of futile surgical interventions that would entail this aggressive attitude must be carefully evaluated. Surgical pleurodesis is recommended and frequently performed to limit recurrences; talc poudrage offers efficient pleurodesis, but a considerable number of surgeons are concerned about administering this inert material to young patients. Clinical trial registration number: International Prospective Register of Systematic Reviews (PROSPERO): CRD42018084247.

Tumors develop within complex cell-to-cell interactions, with accessory cells playing a relevant role starting in the early phases of cancer progression. This event occurs in a three-dimensional (3D) environment, which to date, has been difficult to reproduce in vitro due to its complexity. While bi-dimensional cultures have generated substantial data, there is a progressive awareness that 3D culture strategies may rapidly increase the understanding of tumor development and be used in anti-cancer compound screening and for predicting response to new drugs utilizing personalized approaches. However, simple systems capable of rapidly rebuilding cancer tissues ex-vivo in 3D are needed and could be used for a variety of applications. Therefore, we developed a flat, handheld and versatile 3D cell culture bioreactor that can be loaded with tumor and/or normal cells in combination which can be monitored using a variety of read-outs. This biocompatible device sustained 3D growth of tumor cell lines representative of various cancers, such as pancreatic and breast adenocarcinoma, sarcoma, and glioblastoma. The cells repopulated the thin matrix which was completely separated from the outer space by two gas-permeable membranes and was monitored in real-time using both microscopy and luminometry, even after transportation. The device was tested in 3D cytotoxicity assays to investigate the anti-cancer potential of chemotherapy, biologic agents, and cell-based therapy in co-cultures. The addition of luciferase in target cancer cells is suitable for comparative studies that may also involve parallel in vivo investigations. Notably, the system was challenged using primary tumor cells harvested from lung cancer patients as an innovative predictive functional assay for cancer responsiveness to checkpoint inhibitors, such as nivolumab. This bioreactor has several novel features in the 3D-culture field of research, representing a valid tool useful for cancer investigations, drug screenings, and other toxicology approaches.