Identification of subpopulations with characteristics of mesenchymal progenitor cells from human osteoarthritic cartilage using triple staining for cell surface markers

We first identified and isolated cellular subpopulations with characteristics of mesenchymal progenitor cells (MPCs) in osteoarthritic cartilage using fluorescence-activated cell sorting (FACS). Cells from osteoarthritic cartilage were enzymatically isolated and analyzed directly or after culture expansion over several passages by FACS using various combinations of surface markers that have been identified on human MPCs (CD9, CD44, CD54, CD90, CD166). Culture expanded cells combined and the subpopulation derived from initially sorted CD9(+), CD90(+), CD166(+ )cells were tested for their osteogenic, adipogenic and chondrogenic potential using established differentiation protocols. The differentiation was analyzed by immunohistochemistry and by RT-PCR for the expression of lineage related marker genes. Using FACS analysis we found that various triple combinations of CD9, CD44, CD54, CD90 and CD166 positive cells within osteoarthritic cartilage account for 2–12% of the total population. After adhesion and cultivation their relative amount was markedly higher, with levels between 24% and 48%. Culture expanded cells combined and the initially sorted CD9/CD90/CD166 triple positive subpopulation had multipotency for chondrogenic, osteogenic and adipogenic differentiation. In conclusion, human osteoarthritic cartilage contains cells with characteristics of MPCs. Their relative enrichment during in vitro cultivation and the ability of cell sorting to obtain more homogeneous populations offer interesting perspectives for future studies on the activation of regenerative processes within osteoarthritic joints

Parameters affecting baseline hip function in patients with cam-derived femoroacetabular impingement syndrome: data analysis from the German Cartilage Registry

Background Using the database of the German Cartilage Registry (KnorpelRegister DGOU), this study aims to present patient- and joint-related baseline data in a large cohort of patients with cam-derived femoroacetabular impingement syndrome (FAI) and to detect symptom-determining factors. Materials and methods Requiring cam morphology as the primary pathology, 362 patients were found to be eligible for inclusion in the study. The assessment of preoperative baseline data was performed using the patient-reported outcome measure—International Hip Outcome Tool (iHOT-33). Descriptive statistics were performed to present baseline data. Univariate and multiple regression with post hoc testing were used to identify patient- and joint-related factors that might affect the preoperative iHOT-33 and its subscores, respectively. Results The study collective’s mean age was 36.71 ± 10.89 years, with 246 (68%) of them being male. The preoperative mean iHOT-33 total was 46.31 ± 20.33 with the subsection “sports and recreational activities” presenting the strongest decline (26.49 ± 20.68). The parameters “age,” “sex,” “body mass index” (BMI), and the confirmation of “previous surgery on the affected hip” were identified to statistically affect the preoperative iHOT-33. In fact, a significantly lower mean baseline score was found in patients aged > 40 years (p < 0.001), female sex (p < 0.001), BMI ≥ 25 kg/m2 (p = 0.002) and in patients with previous surgery on the affected hip (p = 0.022). In contrast, the parameters defect grade and size, labral tears, and symptom duration delivered no significant results. Conclusions A distinct reduction in the baseline iHOT-33, with mean total scores being more than halved, was revealed. The parameters “age > 40 years,” “female sex,” “BMI ≥ 25,” and confirmation of “previous surgery on the affected hip” were detected as significantly associated with decreased preoperative iHOT-33 scores. These results help to identify symptom-defining baseline characteristics of cam-derived FAI syndrome. Trial registration: The German Cartilage Registry is conducted in accordance with the Declaration of Helsinki and registered at germanctr.de (DRKS00005617). Registered 3 January 2014—retrospectively registered. The registration of data was approved by the local ethics committees of every participating institution. Primary approval was given by the ethics committee at the University of Freiburg (No. 105/13). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS0000561

Outcome-Affecting Parameters of Hip Arthroscopy for Femoroacetabular Impingement with Concomitant Cartilage Damage—Data Analysis from the German Cartilage Registry

This study aims to report on a prospectively collected, multicenter database of patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAI) and concomitant cartilage damage (according to the International Cartilage Repair Society) and to assess the outcomeaffecting parameters. In the study, 353 hips with up to 24 months’ follow-up were assessed by iHOT-33 scoring and achievement of the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) levels. Multiple and binary regression analyses were performed to identify factors related to (un-) favorable outcomes and to assess their clinical relevance with regard to achieving the MCID and PASS. Multiple regression yielded the parameters of male sex (p = 0.022) and lower body mass index (BMI) (p = 0.019) at 6 months, lower BMI (p = 0.022) and younger age (p = 0.022) at 12 months, and younger age at 24 months (p = 0.039) to be significantly associated with higher iHOT scoring. Male sex (p = 0.019) and lower BMI (p = 0.018) were significantly correlated with achievement of the PASS in binary regression at 6 months, whereas at 12 (p = 0.010) and at 24 (p = 0.003) only younger age was shown to be significantly correlated. None of the parameters was statistically associated with achievement of the MCID. As the parameters of younger age, male sex, and lower BMI were identified as temporarily correlated with a preferable outcome in general and with achievement of the PASS in particular, these findings help to preoperatively identify factors associated with (un-) favorable therapy results

Patients with Small Acetabular Cartilage Defects Caused by Femoroacetabular Impingement Do Not Benefit from Microfracture

Objective: According to current recommendations, large cartilage defects of the hip over 2 cm2 are suggested to undergo autologous chondrocyte transplantation (ACT), while small defects should be treated with microfracture. We investigated if patients with small chondral defects of the hip joint (≤100 mm2 ) actually benefit from microfracture. Design: In this retrospective multicenter cohort study 40 patients with focal acetabular cartilage defects smaller than 100 mm2 and of ICRS grade ≥2 caused by femoroacetabular impingement were included. Twenty-six unrandomized patients underwent microfracture besides treatment of the underlying pathology; in 14 patients cartilage lesions were left untreated during arthroscopy. Over a mean follow-up of 28.8 months patient-reported outcome was determined using the iHOT33 (international hip outcome tool) and the VAS (visual analog scale) for pain. Results: The untreated group showed a statistically significant improvement of the iHOT33 after 12 (p = 0.005), 24 (p = 0.019), and 36 months (p = 0.002) compared to the preoperative score, whereas iHOT33 in the microfracture group did not reveal statistically significant changes over time. There was no significant difference between both groups on any time point. Regarding pain both groups did not show a significant improvement over time in the VAS. Conclusion: The subjective outcome of patients with small cartilage defects of the hip (≤100 mm2 ) improves 12 months after arthroscopic FAIS surgery without any cartilage treatment. However, no improvement could be seen after microfracture. Therefore, a reserved surgical treatment for small cartilage defects of the hip under preservation of the subchondral bone is recommended especially if a simultaneous impingement correction is performed

Interface amorphization of two‐dimensional black phosphorus upon treatment with diazonium salts

Two-dimensional (2D) black phosphorus (BP) represents one of the most appealing 2D materials due to its electronic, optical, and chemical properties. Many strategies have been pursued to face its environmental instability, covalent functionalization being one of the most promising. However, the extremely low functionalization degrees and the limitations in proving the nature of the covalent functionalization still represent challenges in many of these sheet architectures reported to date. Here we shine light on the structural evolution of 2D-BP upon the addition of electrophilic diazonium salts. We demonstrated the absence of covalent functionalization in both the neutral and the reductive routes, observing in the latter case an unexpected interface conversion of BP to red phosphorus (RP), as characterized by Raman, 31P-MAS NMR, and X-ray photoelectron spectroscopies (XPS). Furthermore, thermogravimetric analysis coupled to gas chromatography and mass spectrometry (TG-GC-MS), as well as electron paramagnetic resonance (EPR) gave insights into the potential underlying radical mechanism, suggesting a Sandmeyer-like reaction

Strategic School Improvement Fund: updated 12 September 2017

<p><b>Comparison of MRI (A and B) with histological findings (C).</b> The lateral tibia plateau region of the sham knee joint of animal #8958 showed no salience neither in the sagittal MRI-scan (A) through the lateral compartment of the knee nor in the coronal MRI-scan (B) and was therefore rated as unchanged. The scale bars for A and B were determined with the program RadiAnt DICOM viewer (see caption <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0165897#pone.0165897.g001" target="_blank">Fig 1</a>). In contrast to the MRI results, the histological safranin-o staining (C) showed a moderate degeneration (Little-score: 10.5 points) with a fissure (1) in the cartilage and detachment of the topmost layer of the cartilage tissue. The histological finding and the MRI result did not concur.</p

Unveiling the oxidation behavior of liquid-phase exfoliated antimony nanosheets

Antimonene, a monolayer of β-antimony, is increasingly attracting considerable attention, more than that of other monoelemental two-dimensional materials, due to its intriguing physical and chemical properties. Under ambient conditions, antimonene exhibits a high thermodynamic stability and good structural integrity. Some theoretical calculations predicted that antimonene would have a high oxidation tendency. However, it remains poorly investigated from the experimental point of view. In this work, we study the oxidation behavior of antimonene nanosheets (ANS) prepared by ultrasonication-assisted liquid-phase exfoliation. Using a set of forefront analytical techniques, a clear effect of sonication time on the surface chemistry of prepared ANS is found. A dynamic oxidation behavior has been observed, which upon annealing at moderate temperature (210 °C) resulted in a semiconducting behavior with a bandgap of approximately 1 eV measured by ultraviolet photoelectron spectroscopy. This study yields valuable information for future applications of antimonene and paves the way towards novel modification approaches in order to tailor its properties and complement its limitations

Patients with Small Acetabular Cartilage Defects Caused by Femoroacetabular Impingement Do Not Benefit from Microfracture

Objective: According to current recommendations, large cartilage defects of the hip over 2 cm2 are suggested to undergo autologous chondrocyte transplantation (ACT), while small defects should be treated with microfracture. We investigated if patients with small chondral defects of the hip joint (≤100 mm2) actually benefit from microfracture. Design: In this retrospective multicenter cohort study 40 patients with focal acetabular cartilage defects smaller than 100 mm2 and of ICRS grade ≥2 caused by femoroacetabular impingement were included. Twenty-six unrandomized patients underwent microfracture besides treatment of the underlying pathology; in 14 patients cartilage lesions were left untreated during arthroscopy. Over a mean follow-up of 28.8 months patient-reported outcome was determined using the iHOT33 (international hip outcome tool) and the VAS (visual analog scale) for pain. Results: The untreated group showed a statistically significant improvement of the iHOT33 after 12 (p = 0.005), 24 (p = 0.019), and 36 months (p = 0.002) compared to the preoperative score, whereas iHOT33 in the microfracture group did not reveal statistically significant changes over time. There was no significant difference between both groups on any time point. Regarding pain both groups did not show a significant improvement over time in the VAS. Conclusion: The subjective outcome of patients with small cartilage defects of the hip (≤100 mm2) improves 12 months after arthroscopic FAIS surgery without any cartilage treatment. However, no improvement could be seen after microfracture. Therefore, a reserved surgical treatment for small cartilage defects of the hip under preservation of the subchondral bone is recommended especially if a simultaneous impingement correction is performed

A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer

Aim Chemoresistance is a major cause of treatment failure in colorectal cancer (CRC) therapy. In this study, the impact of the IGF2BP family of RNA-binding proteins on CRC chemoresistance was investigated using in silico, in vitro, and in vivo approaches. Methods Gene expression data from a well-characterized cohort and publicly available cross-linking immunoprecipi‑ tation sequencing (CLIP-Seq) data were collected. Resistance to chemotherapeutics was assessed in patient-derived xenografts (PDXs) and patient-derived organoids (PDOs). Functional studies were performed in 2D and 3D cell culture models, including proliferation, spheroid growth, and mitochondrial respiration analyses. Results We identifed IGF2BP2 as the most abundant IGF2BP in primary and metastastatic CRC, correlating with tumor stage in patient samples and tumor growth in PDXs. IGF2BP2 expression in primary tumor tissue was signif‑ cantly associated with resistance to selumetinib, geftinib, and regorafenib in PDOs and to 5-fuorouracil and oxalipl‑ atin in PDX in vivo. IGF2BP2 knockout (KO) HCT116 cells were more susceptible to regorafenib in 2D and to oxaliplatin, selumitinib, and nintedanib in 3D cell culture. Further, a bioinformatic analysis using CLIP data suggested stabiliza‑ tion of target transcripts in primary and metastatic tumors. Measurement of oxygen consumption rate (OCR) and extracellular acidifcation rate (ECAR) revealed a decreased basal OCR and an increase in glycolytic ATP production rate in IGF2BP2 KO. In addition, real-time reverse transcriptase polymerase chain reaction (qPCR) analysis confrmed decreased expression of genes of the respiratory chain complex I, complex IV, and the outer mitochondrial membrane in IGF2BP2 KO cells. Conclusions IGF2BP2 correlates with CRC tumor growth in vivo and promotes chemoresistance by altering mito‑ chondrial respiratory chain metabolism. As a druggable target, IGF2BP2 could be used in future CRC therapy to overcome CRC chemoresistance