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

A multi-modal dance corpus for research into interaction between humans in virtual environments

We present a new, freely available, multimodal corpus for research into, amongst other areas, real-time realistic interaction between humans in online virtual environments. The specific corpus scenario focuses on an online dance class application scenario where students, with avatars driven by whatever 3D capture technology is locally available to them, can learn choreographies with teacher guidance in an online virtual dance studio. As the dance corpus is focused on this scenario, it consists of student/teacher dance choreographies concurrently captured at two different sites using a variety of media modalities, including synchronised audio rigs, multiple cameras, wearable inertial measurement devices and depth sensors. In the corpus, each of the several dancers performs a number of fixed choreographies, which are graded according to a number of specific evaluation criteria. In addition, ground-truth dance choreography annotations are provided. Furthermore, for unsynchronised sensor modalities, the corpus also includes distinctive events for data stream synchronisation. The total duration of the recorded content is 1 h and 40 min for each single sensor, amounting to 55 h of recordings across all sensors. Although the dance corpus is tailored specifically for an online dance class application scenario, the data is free to download and use for any research and development purposes

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

Peer reviewe

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

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

Mesenchymal stem cell-based therapy for ischemic stroke

Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field

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