Articular cartilage damaged through trauma or disease has a limited ability to repair. Untreated, focal lesions progress to generalized changes including osteoarthritis. Musculoskeletal disorders ...including osteoarthritis are the most significant contributor to disability globally. There is increasing interest in the use of mesenchymal stem cells (MSCs) for the treatment of focal chondral lesions. There is some evidence to suggest that the tissue type from which MSCs are harvested play a role in determining their ability to regenerate cartilage
in vitro
and
in vivo
. In humans, MSCs derived from synovial tissue may have superior chondrogenic potential. We carried out a systematic literature review on the effectiveness of synovium-derived MSCs (sMSCs) in cartilage regeneration in
in vivo
studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Twenty studies were included in our review; four examined the use of human sMSCs and 16 were conducted using sMSCs harvested from animals. Most studies reported successful cartilage repair with sMSC transplantation despite the variability of animals, cell harvesting techniques, methods of delivery, and outcome measures. We conclude that sMSC transplantation holds promise as a treatment option for focal cartilage defects. We believe that defining the cell population being used, establishing standardized methods for MSC delivery, and the use of objective outcome measures should enable future high quality studies such as randomized controlled clinical trials to provide the evidence needed to manage chondral lesions optimally.
Damage to joints through injury or disease can result in cartilage loss, which if left untreated can lead to inflammation and ultimately osteoarthritis. There is currently no cure for osteoarthritis ...and management focusses on symptom control. End-stage osteoarthritis can be debilitating and ultimately requires joint replacement in order to maintain function. Therefore, there is growing interest in innovative therapies for cartilage repair. In this systematic literature review, we sought to explore the
in vivo
evidence for the use of human Mesenchymal Stem Cell-derived Extracellular Vesicles (MSC-EVs) for treating cartilage damage. We conducted a systematic literature review in accordance with the PRISMA protocol on the evidence for the treatment of cartilage damage using human MSC-EVs. Studies examining
in vivo
models of cartilage damage were included. A risk of bias analysis of the studies was conducted using the SYRCLE tool. Ten case-control studies were identified in our review, including a total of 159 murine subjects. MSC-EVs were harvested from a variety of human tissues. Five studies induced osteoarthritis, including cartilage loss through surgical joint destabilization, two studies directly created osteochondral lesions and three studies used collagenase to cause cartilage loss. All studies in this review reported reduced cartilage loss following treatment with MSC-EVs, and without significant complications. We conclude that transplantation of MSC-derived EVs into damaged cartilage can effectively reduce cartilage loss in murine models of cartilage injury. Additional randomized studies in animal models that recapitulates human osteoarthritis will be necessary in order to establish findings that inform clinical safety in humans.
The most common pattern seen in bilateral knee osteoarthritis involves only the medial compartment in both knees. In such cases, bilateral Unicompartmental Knee Arthroplasty (UKA) would be a suitable ...surgery, this can be done simultaneously in one surgery or in stages with a period of time between each UKA. Simultaneous bilateral UKA in appropriately selected patients have the potential advantages of a lower cost, a shorter hospital stay, and a shorter overall recovery process. Despite this, there are concerns that operating on both knees in one surgery may increase the risk of complications, revisions and mortality.
A PRISMA systematic review and meta-analysis was conducted using three databases (MEDLINE, EMBASE, and Scopus) to identify all studies which investigated either clinical or radiological outcomes in simultaneous bilateral UKA.
All sixteen studies included found that simultaneous bilateral UKA improved clinical and radiological outcomes. Eight studies compared clinical or radiological outcomes between simultaneous and staged bilateral UKA. Simultaneous bilateral UKA was found to have a significantly shorter length of operation, length of hospital stay, and a lower treatment cost (P < 0.001). Our meta-analysis found no statistically significant difference in the all-cause complication rate between simultaneous and staged bilateral UKA (P = 0.36). Only one study compared radiological outcomes between simultaneous and staged bilateral UKA which found no significant difference.
Our review suggests that simultaneous bilateral UKA is comparable to staged bilateral UKA in terms of clinical and radiological outcomes and has the potential to be increasingly adopted in clinical practice due to its superior cost-effectiveness.
Circumstellar disks are an essential ingredient of the formation of low-mass stars. It is unclear, however, whether the accretion-disk paradigm can also account for the formation of stars more ...massive than about 10 solar masses, in which strong radiation pressure might halt mass infall. Massive stars may form by stellar merging, although more recent theoretical investigations suggest that the radiative-pressure limit may be overcome by considering more complex, non-spherical infall geometries. Clear observational evidence, such as the detection of compact dusty disks around massive young stellar objects, is needed to identify unambiguously the formation mode of the most massive stars. Here we report near-infrared interferometric observations that spatially resolve the astronomical-unit-scale distribution of hot material around a high-mass (∼20 solar masses) young stellar object. The image shows an elongated structure with a size of ∼13 × 19 astronomical units, consistent with a disk seen at an inclination angle of ∼45°. Using geometric and detailed physical models, we found a radial temperature gradient in the disk, with a dust-free region less than 9.5 astronomical units from the star, qualitatively and quantitatively similar to the disks observed in low-mass star formation. Perpendicular to the disk plane we observed a molecular outflow and two bow shocks, indicating that a bipolar outflow emanates from the inner regions of the system.
Advances in phenology (the annual timing of species' life-cycles) in response to climate change are generally viewed as bioindicators of climate change, but have not been considered as predictors of ...range expansions. Here, we show that phenology advances combine with the number of reproductive cycles per year (voltinism) to shape abundance and distribution trends in 130 species of British Lepidoptera, in response to ~0.5 °C spring-temperature warming between 1995 and 2014. Early adult emergence in warm years resulted in increased within- and between-year population growth for species with multiple reproductive cycles per year (n = 39 multivoltine species). By contrast, early emergence had neutral or negative consequences for species with a single annual reproductive cycle (n = 91 univoltine species), depending on habitat specialisation. We conclude that phenology advances facilitate polewards range expansions in species exhibiting plasticity for both phenology and voltinism, but may inhibit expansion by less flexible species.
Neural signatures of sleep in zebrafish Leung, Louis C; Wang, Gordon X; Madelaine, Romain ...
Nature (London),
07/2019, Letnik:
571, Številka:
7764
Journal Article
Recenzirano
Odprti dostop
Slow-wave sleep and rapid eye movement (or paradoxical) sleep have been found in mammals, birds and lizards, but it is unclear whether these neuronal signatures are found in non-amniotic vertebrates. ...Here we develop non-invasive fluorescence-based polysomnography for zebrafish, and show-using unbiased, brain-wide activity recording coupled with assessment of eye movement, muscle dynamics and heart rate-that there are at least two major sleep signatures in zebrafish. These signatures, which we term slow bursting sleep and propagating wave sleep, share commonalities with those of slow-wave sleep and paradoxical or rapid eye movement sleep, respectively. Further, we find that melanin-concentrating hormone signalling (which is involved in mammalian sleep) also regulates propagating wave sleep signatures and the overall amount of sleep in zebrafish, probably via activation of ependymal cells. These observations suggest that common neural signatures of sleep may have emerged in the vertebrate brain over 450 million years ago.
Bathymetry (seafloor depth), is a critical parameter providing the geospatial context for a multitude of marine scientific studies. Since 1997, the International Bathymetric Chart of the Arctic Ocean ...(IBCAO) has been the authoritative source of bathymetry for the Arctic Ocean. IBCAO has merged its efforts with the Nippon Foundation-GEBCO-Seabed 2030 Project, with the goal of mapping all of the oceans by 2030. Here we present the latest version (IBCAO Ver. 4.0), with more than twice the resolution (200 × 200 m versus 500 × 500 m) and with individual depth soundings constraining three times more area of the Arctic Ocean (∼19.8% versus 6.7%), than the previous IBCAO Ver. 3.0 released in 2012. Modern multibeam bathymetry comprises ∼14.3% in Ver. 4.0 compared to ∼5.4% in Ver. 3.0. Thus, the new IBCAO Ver. 4.0 has substantially more seafloor morphological information that offers new insights into a range of submarine features and processes; for example, the improved portrayal of Greenland fjords better serves predictive modelling of the fate of the Greenland Ice Sheet.
Despite the resounding clinical success in cancer treatment of antibodies that block the interaction of PD1 with its ligand PDL1
, the mechanisms involved remain unknown. A major limitation to ...understanding the origin and fate of T cells in tumour immunity is the lack of quantitative information on the distribution of individual clonotypes of T cells in patients with cancer. Here, by performing deep single-cell sequencing of RNA and T cell receptors in patients with different types of cancer, we survey the profiles of various populations of T cells and T cell receptors in tumours, normal adjacent tissue, and peripheral blood. We find clear evidence of clonotypic expansion of effector-like T cells not only within the tumour but also in normal adjacent tissue. Patients with gene signatures of such clonotypic expansion respond best to anti-PDL1 therapy. Notably, expanded clonotypes found in the tumour and normal adjacent tissue can also typically be detected in peripheral blood, which suggests a convenient approach to patient identification. Analyses of our data together with several external datasets suggest that intratumoural T cells, especially in responsive patients, are replenished with fresh, non-exhausted replacement cells from sites outside the tumour, suggesting continued activity of the cancer immunity cycle in these patients, the acceleration of which may be associated with clinical response.
In order to assess the therapeutic potential of cell-based strategies, it is of paramount importance to elaborate and validate tools for monitoring the behavior of injected cells in terms of tissue ...dissemination and engraftment properties. Here, we apply bismuth ferrite harmonic nanoparticles (BFO HNPs) to in vitro expanded human skeletal muscle-derived stem cells (hMuStem cells), an attractive therapeutic avenue for patients suffering from Duchenne muscular dystrophy (DMD). We demonstrate the possibility of stem cell labeling with HNPs. We also show that the simultaneous acquisition of second- and third-harmonic generation (SHG and THG) from BFO HNPs helps separate their response from tissue background, with a net increase in imaging selectivity, which could be particularly important in pathologic context that is defined by a highly remodelling tissue. We demonstrate the possibility of identifying <100 nm HNPs in depth of muscle tissue at more than 1 mm from the surface, taking full advantage of the extended imaging penetration depth allowed by multiphoton microscopy in the second near-infrared window (NIR-II). Based on this successful assessment, we monitor over 14 days any modification on proliferation and morphology features of hMuStem cells upon exposure to PEG-coated BFO HNPs at different concentrations, revealing their high biocompatibility. Successively, we succeed in detecting individual HNP-labeled hMuStem cells in skeletal muscle tissue after their intramuscular injection.
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