Role of mesenchymal stem cells in osteosarcoma and metabolic reprogramming of tumor cells

The tumor microenvironment plays an important role in cancer progression. Here, we focused on the role of reactive mesenchymal stem cells (MSC) in osteosarcoma (OS), and used human adipose MSC and a panel of OS cell lines (Saos-2, HOS, and 143B) to investigate the mutual effect of normal-cancer cell metabolic programming. Our results showed that MSC are driven by oxidative stress induced by OS cells to undergo Warburg metabolism, with increased lactate production. Therefore, we analyzed the expression of lactate monocarboxylate transporters. By real time PCR and immunofluorescence, in MSC we detected the expression of MCT-4, the transporter for lactate efflux, whereas MCT-1, responsible for lactate uptake, was expressed in OS cells. In agreement, silencing of MCT-1 by siRNA significantly affected the ATP production in OS cancer cells. Thus, cancer cells directly increase their mitochondrial biogenesis using this energy-rich metabolite that is abundantly provided by MSC as an effect of the altered microenvironmental conditions induced by OS cells. We also showed that lactate produced by MSC promotes the migratory ability of OS cells. These data provide novel information to be exploited for cancer therapies targeting the mutual metabolic reprogramming of cancer cells and their stroma.The tumor microenvironment plays an important role in cancer progression. Here, we focused on the role of reactive mesenchymal stem cells (MSC) in osteosarcoma (OS), and used human adipose MSC and a panel of OS cell lines (Saos-2, HOS, and 143B) to investigate the mutual effect of normal-cancer cell metabolic programming. Our results showed that MSC are driven by oxidative stress induced by OS cells to undergo Warburg metabolism, with increased lactate production. Therefore, we analyzed the expression of lactate monocarboxylate transporters. By real time PCR and immunofluorescence, in MSC we detected the expression of MCT-4, the transporter for lactate efflux, whereas MCT-1, responsible for lactate uptake, was expressed in OS cells. In agreement, silencing of MCT-1 by siRNA significantly affected the ATP production in OS cancer cells. Thus, cancer cells directly increase their mitochondrial biogenesis using this energy-rich metabolite that is abundantly provided by MSC as an effect of the altered microenvironmental conditions induced by OS cells. We also showed that lactate produced by MSC promotes the migratory ability of OS cells. These data provide novel information to be exploited for cancer therapies targeting the mutual metabolic reprogramming of cancer cells and their stroma

Quantifying the Effects of Ethanol and Temperature on the Fitness Advantage of Predominant Saccharomyces cerevisiae Strains Occurring in Spontaneous Wine Fermentations

Different Saccharomyces cerevisiae strains are simultaneously or in succession involved in spontaneous wine fermentations. In general, few strains occur at percentages higher than 50% of the total yeast isolates (predominant strains), while a variable number of other strains are present at percentages much lower (secondary strains). Since S. cerevisiae strains participating in alcoholic fermentations may differently affect the chemical and sensory qualities of resulting wines, it is of great importance to assess whether the predominant strains possess a “dominant character.” Therefore, the aim of this study was to investigate whether the predominance of some S. cerevisiae strains results from a better adaptation capability (fitness advantage) to the main stress factors of oenological interest: ethanol and temperature. Predominant and secondary S. cerevisiae strains from different wineries were used to evaluate the individual effect of increasing ethanol concentrations (0-3-5 and 7% v/v) as well as the combined effects of different ethanol concentrations (0-3-5 and 7% v/v) at different temperature (25–30 and 35°C) on yeast growth. For all the assays, the lag phase period, the maximum specific growth rate (μmax) and the maximum cell densities were estimated. In addition, the fitness advantage between the predominant and secondary strains was calculated. The findings pointed out that all the predominant strains showed significantly higher μmax and/or lower lag phase values at all tested conditions. Hence, S. cerevisiae strains that occur at higher percentages in spontaneous alcoholic fermentations are more competitive, possibly because of their higher capability to fit the progressively changing environmental conditions in terms of ethanol concentrations and temperature

Preparation method and growth factor content of platelet concentrate influence the osteogenic differentiation of bone marrow stromal cells

n/

Enhancing Osteoconduction of PLLA-Based Nanocomposite Scaffolds for Bone Regeneration Using Different Biomimetic Signals to MSCs

In bone engineering, the adhesion, proliferation and differentiation of mesenchymal stromal cells rely on signaling from chemico-physical structure of the substrate, therefore prompting the design of mimetic “extracellular matrix”-like scaffolds. In this study, three-dimensional porous poly-L-lactic acid (PLLA)-based scaffolds have been mixed with different components, including single walled carbon nanotubes (CNT), micro-hydroxyapatite particles (HA), and BMP2, and treated with plasma (PT), to obtain four different nanocomposites: PLLA + CNT, PLLA + CNTHA, PLLA + CNT + HA + BMP2 and PLLA + CNT + HA + PT. Adult bone marrow mesenchymal stromal cells (MSCs) were derived from the femur of orthopaedic patients, seeded on the scaffolds and cultured under osteogenic induction up to differentiation and mineralization. The release of specific metabolites and temporal gene expression profiles of marrow-derived osteoprogenitors were analyzed at definite time points, relevant to in vitro culture as well as in vivo differentiation. As a result, the role of the different biomimetic components added to the PLLA matrix was deciphered, with BMP2-added scaffolds showing the highest biomimetic activity on cells differentiating to mature osteoblasts. The modification of a polymeric scaffold with reinforcing components which also work as biomimetic cues for cells can effectively direct osteoprogenitor cells differentiation, so as to shorten the time required for mineralization

Epineurotomy of the median nerve in carpal tunnel release: a systematic review and an attempt of metanalysis

The role of epineurolysis in carpal tunnel release is not clear, and its inclusion or not in the standard practice is a subjective choice of the hand surgeon based on their training and experience rather than being based on evidence. A systematic review with metanalysis of randomized controlled trials comparing median nerve decompression at the carpal tunnel with or without the adjunct of epineurolysis was attempted, in order to define whether or not this is an effective procedure. From the metanalysis of the general postoperative outcome, no advantage seems to derive from epineurolysis. On the contrary, if the Tinel's sign is used for the equivalent analysis, an impression favoring epineurolysis is obtained. However, a definitive answer to the utility or not of this procedure can only be achieved through large and accurate randomized prospective controlled studies, possibly including a subdivision of patients into groups based on comorbidities

Negative pressure treatment for improvement of surgical wounds after circumferential thigh lift

The circumferential thigh lift (CTL) with vertical scar is a more extensive and effective procedure compared to the traditional lift, but the scar is not aequally concealed. Negative pressure treatment (NPT) is considered to have a beneficial effect on the physiological process of wound healing and early scar formation. A comparison study was therefore carried out in order to evaluate the effect of NPT on scar quality

Biological effects of metal degradation in hip arthroplasties

Metals and metal alloys are the most used materials in orthopedic implants. The focus is on total hip arthroplasty (THA) that, though well tolerated, may be associated with local and remote adverse effects in the medium-long term. This review aims to summarize data on the biological consequences of the metal implant degradation that have been attributed predominantly to metal-on-metal (MoM) THA. Local responses to metals consist of a broad clinical spectrum ranging from small asymptomatic tissue lesions to severe destruction of bone and soft tissues, which are designated as metallosis, adverse reactions to metal debris (ARMD), aseptic lymphocytic vasculitis associated lesion (ALVAL), and pseudotumors. In addition, the dissemination of metal particles and ions throughout the body has been associated with systemic adverse effects, including organ toxicity, cancerogenesis, teratogenicity, and immunotoxicity. As proved by the multitude of studies in this field, metal degradation may increase safety issues associated with THA, especially with MoM hip systems. Data collection regarding local, systemic and long-term effects plays an essential role to better define any safety risks and to generate scientifically based recommendations

Role of Citrate in Pathophysiology and Medical Management of Bone Diseases

Citrate is an intermediate in the “Tricarboxylic Acid Cycle” and is used by all aerobic organisms to produce usable chemical energy. It is a derivative of citric acid, a weak organic acid which can be introduced with diet since it naturally exists in a variety of fruits and vegetables, and can be consumed as a dietary supplement. The close association between this compound and bone was pointed out for the first time by Dickens in 1941, who showed that approximately 90% of the citrate bulk of the human body resides in mineralised tissues. Since then, the number of published articles has increased exponentially, and considerable progress in understanding how citrate is involved in bone metabolism has been made. This review summarises current knowledge regarding the role of citrate in the pathophysiology and medical management of bone disorders