Paracrine effects of TLR4-polarised mesenchymal stromal cells are mediated by extracellular vesicles

Mesenchymal stromal cells (MSCs) are adult stem cells able to give rise to bone, cartilage and fat cells. In addition, they possess immunomodulatory and immunosuppressive properties that are mainly mediated through secretion of extracellular vesicles (EVs). In a previous issue of Journal of Translational Medicine, Ti and colleagues demonstrated that preconditioning of MSCs with bacterial lipopolysaccharides results in secretion of EVs that can polarise mac‑ rophages towards anti-inflammatory M2 phenotype. Moreover, the authors suggest that EVs of lipopolysaccharide (LPS)-treated MSCs are superior to EVs of untreated MSCs concerning their ability to support wound healing. Our commentary critically discusses parallel efforts of other laboratories to generate conditioned media from stem cells for therapeutic applications, and highlights impact and significance of the study of Ti et al. Finally, we summarise its limitations and spotlight areas that need to be addressed to better define the underlying molecular mechanisms

Integration of satellite remote sensing data in ecosystem modelling at local scales: Practices and trends

1. Spatiotemporal ecological modelling of terrestrial ecosystems relies on climatological and biophysical Earth observations. Due to their increasing availability, global coverage, frequent acquisition and high spatial resolution, satellite remote sensing (SRS) products are frequently integrated to in situ data in the development of ecosystem models (EMs) quantifying the interaction among the vegetation component and the hydrological, energy and nutrient cycles. This review highlights the main advances achieved in the last decade in combining SRS data with EMs, with particular attention to the challenges modellers face for applications at local scales (e.g. small watersheds). 2. We critically review the literature on progress made towards integration of SRS data into terrestrial EMs: (1) as input to define model drivers; (2) as reference to validate model results; and (3) as a tool to sequentially update the state variables, and to quantify and reduce model uncertainty. 3. The number of applications provided in the literature shows that EMs may profit greatly from the inclusion of spatial parameters and forcings provided by vegetation and climatic‐related SRS products. Limiting factors for the application of such models to local scales are: (1) mismatch between the resolution of SRS products and model grid; (2) unavailability of specific products in free and public online repositories; (3) temporal gaps in SRS data; and (4) quantification of model and measurement uncertainties. This review provides examples of possible solutions adopted in recent literature, with particular reference to the spatiotemporal scales of analysis and data accuracy. We propose that analysis methods such as stochastic downscaling techniques and multi‐sensor/multi‐platform fusion approaches are necessary to improve the quality of SRS data for local applications. Moreover, we suggest coupling models with data assimilation techniques to improve their forecast abilities. 4. This review encourages the use of SRS data in EMs for local applications, and underlines the necessity for a closer collaboration among EM developers and remote sensing scientists. With more upcoming satellite missions, especially the Sentinel platforms, concerted efforts to further integrate SRS into modelling are in great demand and these types of applications will certainly proliferate

Future Perspectives of Bone Tissue Engineering with Special Emphasis on Extracellular Vesicles

Peer reviewe

RNA interference approaches for treatment of HIV-1 infection

HIV/AIDS is a chronic and debilitating disease that cannot be cured with current antiretroviral drugs. While combinatorial antiretroviral therapy (cART) can potently suppress HIV-1 replication and delay the onset of AIDS, viral mutagenesis often leads to viral escape from multiple drugs. In addition to the pharmacological agents that comprise cART drug cocktails, new biological therapeutics are reaching the clinic. These include gene-based therapies that utilize RNA interference (RNAi) to silence the expression of viral or host mRNA targets that are required for HIV-1 infection and/or replication. RNAi allows sequence-specific design to compensate for viral mutants and natural variants, thereby drastically expanding the number of therapeutic targets beyond the capabilities of cART. Recent advances in clinical and preclinical studies have demonstrated the promise of RNAi therapeutics, reinforcing the concept that RNAi-based agents might offer a safe, effective, and more durable approach for the treatment of HIV/AIDS. Nevertheless, there are challenges that must be overcome in order for RNAi therapeutics to reach their clinical potential. These include the refinement of strategies for delivery and to reduce the risk of mutational escape. In this review, we provide an overview of RNAi-based therapies for HIV-1, examine a variety of combinatorial RNAi strategies, and discuss approaches for ex vivo delivery and in vivo delivery

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addresse

Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells

As populations age across the world, osteoporosis and osteoporosis-related fractures are becoming the most prevalent degenerative bone diseases. More than 75 million patients suffer from osteoporosis in the US, the EU and Japan. Furthermore, it is anticipated that the number of patients affected by osteoporosis will increase by a third by 2050. Although conventional therapies including bisphosphonates, calcitonin and oestrogen-like drugs can be used to treat degenerative diseases, they are often associated with serious side effects including the development of oesophageal cancer, ocular inflammation, severe musculoskeletal pain, and osteonecrosis of the jaw. The use of autologous mesenchymal stromal cells/mesenchymal stem cells (MSCs) is a possible alternative therapeutic approach to tackle osteoporosis while overcoming the limitations of traditional treatment options. However, osteoporosis can cause a decrease in the numbers of MSCs, induce their senescence, and lower their osteogenic differentiation potential. Three-dimensional (3D) cell culture is an emerging technology that allows a more physiological expansion and differentiation of stem cells compared to cultivation on conventional flat systems. This review will discuss current understanding of the effects of different 3D cell culture systems on proliferation, viability, osteogenic differentiation, as well as on the immunomodulatory and anti-inflammatory potential of MSCs

Automatic inundation mapping using sentinel-2 data applicable to both Camargue and Do?ana biosphere reserves.

Flooding periodicity is crucial for biomass production and ecosystem functions in wetland areas. Local monitoring networks may be enriched by spaceborne derived products with a temporal resolution of a few days. Unsupervised computer vision techniques are preferred, since human interference and the use of training data may be kept to a minimum. Recently, a novel automatic local thresholding unsupervised methodology for separating inundated areas from non-inundated ones led to successful results for the Do?ana Biosphere Reserve. This study examines the applicability of this approach to Camarque Biosphere Reserve, and proposes alternatives to the original approach to enhance accuracy and applicability for both Camargue and Do?ana wetlands in a scientific quest for methods that may serve accurately biomes at both protected areas. In particular, it examines alternative inputs for automatically estimating thresholds while applying various algorithms for estimating the splitting thresholds. Reference maps for Camargue are provided by local authorities, and generated using Sentinel-2 Band 8A (NIR) and Band 12 (SWIR-2). The alternative approaches examined led to high inundation mapping accuracy. In particular, for the Camargue study area and 39 different dates, the alternative approach with the highest overall Kappa cofficient is 0.84, while, for the Do?ana Biosphere Reserve and Do?ana marshland (a subset of Do?ana Reserve) and 7 different dates, is 0.85 and 0.94, respectively. Moreover, there are alternative approaches with high overall Kappa for all areas, i.e., at 0.79 for Camargue, over 0.91 for Do?ana marshland, and over 0.82 for Do?ana Reserve. Additionally, this study identifies the alternative approaches that perform better when the study area is extensively covered by temporary flooded and emergent vegetation areas (i.e., Camargue Reserve and Do?ana marshland) or when it contains a large percentage of dry areas (i.e., Do?ana Reserve). The development of credible automatic thresholding techniques that can be applied to different wetlands could lead to a higher degree of automation for map production, while enhancing service utilization by non-trained personnel