BackgroundArticular cartilage displays a poor repair capacity. The aim of cell-based therapies for cartilage defects is to repair damaged joint surfaces with a functional replacement tissue. Currently, chondrocytes removed from a healthy region of the cartilage are used but they are unable to retain their phenotype in expanded culture. The resulting repair tissue is fibrocartilaginous rather than hyaline, potentially compromising long-term repair. Mesenchymal stem cells, particularly bone marrow stromal cells (BMSC), are of interest for cartilage repair due to their inherent replicative potential. However, chondrocyte differentiated BMSCs display an endochondral phenotype, that is, can terminally differentiate and form a calcified matrix, leading to failure in long-term defect repair. Here, we investigate the isolation and characterisation of a human cartilage progenitor population that is resident within permanent adult articular cartilage.Methods and FindingsHuman articular cartilage samples were digested and clonal populations isolated using a differential adhesion assay to fibronectin. Clonal cell lines were expanded in growth media to high population doublings and karyotype analysis performed. We present data to show that this cell population demonstrates a restricted differential potential during chondrogenic induction in a 3D pellet culture system. Furthermore, evidence of high telomerase activity and maintenance of telomere length, characteristic of a mesenchymal stem cell population, were observed in this clonal cell population. Lastly, as proof of principle, we carried out a pilot repair study in a goat in vivo model demonstrating the ability of goat cartilage progenitors to form a cartilage-like repair tissue in a chondral defect.ConclusionsIn conclusion, we propose that we have identified and characterised a novel cartilage progenitor population resident in human articular cartilage which will greatly benefit future cell-based cartilage repair therapies due to its ability to maintain chondrogenicity upon extensive expansion unlike full-depth chondrocytes that lose this ability at only seven population doublings.

Seismic reflections from gas sands exhibit a wide range of amplitude-versus-offset (AVa) characteristics. The two factors that most strongly determine the Ava behavior of a gas-sand reflection are the normal incidence reflection coefficient R o and the contrast in Poisson's ratio at the reflector. Of these two factors, R o is the least constrained. Based on their Ava characteristics, gas-sand reflectors can be grouped into three classes defined in terms of R o at the top of the gas sand.Class I gas sands have higher impedance than the encasing shale with relatively large positive values for R o . Class 2 gas sands have nearly the same impedance as the encasing shale and are characterized by values of R o near zero. Class 3 sands have lower impedance than the encasing shale with negative, large magnitude values for R o ' Each of these sand classes has a distinct Ava characteristic

In recent years it has become increasingly clear that articular cartilage harbours a viable pool of progenitor cells and interest has focussed on their role during development and disease. Analysis of progenitor numbers using fluorescence-activated sorting techniques has resulted in wide-ranging estimates, which may be the result of context-dependent expression of cell surface markers. We have used a colony-forming assay to reliably determine chondroprogenitor numbers in normal and osteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P  < 0.0001). Intriguingly, cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilage revealed the presence of a divergent progenitor subpopulation characterised by an early senescent phenotype. Divergent sub-populations displayed increased senescence-associated β–galactosidase activity, lower average telomere lengths but retained the capacity to undergo multi-lineage differentiation. Osteoarthritis is an age-related disease and cellular senescence is predicted to be a significant component of the pathological process. This study shows that although early senescence is an inherent property of a subset of activated progenitors, there is also a pool of progenitors with extended viability and regenerative potential residing within osteoarthritic cartilage.

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ObjectivesOsteoarthritis (OA) is a debilitating disease affecting more than 4 million people in the United Kingdom. Despite its prevalence, there is no successful cell-based therapy currently used to treat patients whose cartilage is deemed irrecoverable. The present study aimed to isolate stem cells from tibial plateaux cartilage obtained from patients who underwent total knee replacements for OA and investigate their stem cell characteristics.DesignClonally derived cell lines were selected using a differential adhesion assay to fibronectin and expanded in monolayer culture. Colony forming efficiencies and growth kinetics were investigated. The potential for tri-lineage differentiation into chondrogenic, osteogenic, and adipogenic phenotypes were analyzed using histological stains, immunocytochemistry, and reverse transcriptase polymerase chain reaction.ResultsColony forming cells were successfully isolated from osteoarthritic cartilage and extensively expanded in monolayer culture. Colony forming efficiencies were consistently below 0.1%. Clonal cell lines were expanded beyond 40 population doublings but disparities were observed in the number of population doublings per day. Clonally derived cell lines also demonstrated in vitro multilineage potential via successful differentiation into chondrogenic, osteogenic, and adipogenic lineages. However, variation in the degree of differentiation was observed between these clonal cell lines.ConclusionsA viable pool of cells with stem cell characteristics have been identified within human osteoarthritic cartilage. Variation in the degree of differentiation suggests the possibility of further subpopulations of cells. The identification of this stem cell population highlights the reparative potential of these cells in osteoarthritic cartilage, which could be further exploited to aid the field of regenerative medicine.

Deletion of distal 6p is associated with a distinctive clinical phenotype including Axenfeld-Rieger malformation, hearing loss, congenital heart disease, dental anomalies, developmental delay, and a characteristic facial appearance. We report the case of a child where recognition of the specific ocular and facial phenotype, led to identification of a 6p microdeletion arising from a de novo 6:18 translocation. Detailed analysis confirmed deletion of the FOXC1 forkhead gene cluster at 6p25. CNS anomalies included hydrocephalus and hypoplasia of the cerebellum, brainstem, and corpus callosum with mild to moderate developmental delay. Unlike previous reports, hearing was normal.

Low Schottky barrier height contacts to nCdTe using rareearth metals On the relationship between the surface composition of the substrate and the Schottky barrier height in Au/n CdTe contacts

The quantum-mechanical convergent kinetic equation of Gould and DeWitt is used for the calculation of static transport coefficients through first order in the plasma parameter for a fully ionized, nondengenerate, two-component plasma near thermal equilibrium. The equation is solved with the standard Chapman-Enskog procedure using a three-term Sonine polynomial expansion. Since close collisions and dynamic screening effects are treated correctly, the results contain both logarithmic (dominant) and nonlogarithmic (subdominant) terms evaluated exactly to first order in the plasma parameter. Since close collisions are treated quantum mechanically the transport coefficients obtained are valid for a wide range of temperatures. For the case where only one Sonine polynomial is used in the evaluation of the electrical conductivity, the result obtained here reduces to that of Kivelson and DuBois in the high-temperature limit (kT ≫ Ry) and to that of Gould and DeWitt in the low-temperature, classical limit (kT ≪ Ry). Using more than one Sonine polynomial in the expansion of the distribution function, we obtain for the electrical conductivity σ(χ) = c(χ)σ(1), where χ is the number of terms in the Sonine expansion and σ(1) is the result for one term. In the limit where the Coulomb logarithm is large, c(3) = 1.95 and c(∞) = 1.973, so that our results are accurate to 1 or 2% for a wide range of temperatures (including kT ∼ Ry).