The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

New Genetic Loci Associated with Preharvest Sprouting and Its Evaluation Based on the Model Equation in Rice

Preharvest sprouting (PHS) in rice panicles is an important quantitative trait that causes both yield losses and the deterioration of grain quality under unpredictable moisture conditions at the ripening stage. However, the molecular mechanism underlying PHS has not yet been elucidated. Here, we explored the genetic loci associated with PHS in rice and formulated a model regression equation for rapid screening for use in breeding programs. After re-sequencing 21 representative accessions for PHS and performing enrichment analysis, we found that approximately 20,000 SNPs revealed distinct allelic distributions between PHS resistant and susceptible accessions. Of these, 39 candidate SNP loci were selected, including previously reported QTLs. We analyzed the genotypes of 144 rice accessions to determine the association between PHS and the 39 candidate SNP loci, 10 of which were identified as significantly affecting PHS based on allele type. Based on the allele types of the SNP loci, we constructed a regression equation for evaluating PHS, accounting for an R2 value of 0.401 in japonica rice. We validated this equation using additional accessions, which exhibited a significant R2 value of 0.430 between the predicted values and actual measurements. The newly detected SNP loci and the model equation could facilitate marker-assisted selection to predict PHS in rice germplasm and breeding lines

A practical method for the detection of freezing of gait in patients with Parkinson’s disease

Yuri Kwon,1 Sang Hoon Park,1 Ji-Won Kim,1 Yeji Ho,1 Hyeong-Min Jeon,1 Min-Jung Bang,1 Gu-In Jung,1 Seon-Min Lee,3 Gwang-Moon Eom,1,2 Seong-Beom Koh,3 Jeong-Whan Lee,1,2 Heung Seok Jeon41Biomedical Engineering, 2Research Institute of Biomedical Engineering, Konkuk University, Chungju, Korea; 3Department of Neurology, Korea University College of Medicine, Seoul, Korea; 4Department of Computer Engineering, Konkuk University, Chungju, KoreaPurpose: Freezing of gait (FOG), increasing the fall risk and limiting the quality of life, is common at the advanced stage of Parkinson’s disease, typically in old ages. A simple and unobtrusive FOG detection system with a small calculation load would make a fast presentation of on-demand cueing possible. The purpose of this study was to find a practical FOG detection system.Patients and methods: A sole-mounted sensor system was developed for an unobtrusive measurement of acceleration during gait. Twenty patients with Parkinson’s disease participated in this study. A simple and fast time-domain method for the FOG detection was suggested and compared with the conventional frequency-domain method. The parameters used in the FOG detection were optimized for each patient.Results: The calculation load was 1,154 times less in the time-domain method than the conventional method, and the FOG detection performance was comparable between the two domains (P=0.79) and depended on the window length (P<0.01) and dimension of sensor information (P=0.03). Conclusion: A minimally constraining sole-mounted sensor system was developed, and the suggested time-domain method showed comparable FOG detection performance to that of the conventional frequency-domain method. Three-dimensional sensor information and 3–4-second window length were desirable. The suggested system is expected to have more practical clinical applications.Keywords: Parkinson’s disease, freezing of gait, acceleration, detection system, time-domain, frequency-domai

Effect of Ketorolac on the Prevention of Postoperative Catheter-Related Bladder Discomfort in Patients Undergoing Robot-Assisted Laparoscopic Radical Prostatectomy: A Randomized, Double-Blinded, Placebo-Controlled Study

Urinary catheterization can cause catheter-related bladder discomfort (CRBD). Ketorolac is widely used for pain control. Therefore, we evaluated the effect of ketorolac on the prevention of CRBD in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALP). All patients were randomly allocated to the ketorolac group or the control group. The primary outcome was CRBD above a moderate grade at 0 h postoperatively. CRBD above a moderate grade at 1, 2, and 6 h was also assessed. Postoperative pain, opioid requirement, ketorolac-related complications, patient satisfaction, and hospitalization duration were also assessed. The incidence of CRBD above a moderate grade at 0 h postoperatively was significantly lower in the ketorolac group (21.5% vs. 50.8%, p = 0.001) as were those at 1, 2, and 6 h. Pain scores at 0 and 1 h and opioid requirement over 24 h were significantly lower in the ketorolac group, while patient satisfaction scores were significantly higher in the ketorolac group. Ketorolac-related complications and hospitalization duration were not significantly different between the two groups. This study shows ketorolac can reduce postoperative CRBD above a moderate grade and increase patient satisfaction in patients undergoing RALP, suggesting it is a useful option to prevent postoperative CRBD

Comparison of hepatic fat fraction (%) in dual- and triple-echo MRI.

<p>The dual-echo fat fraction (mean 2.3 ± 2.0%) was not different from the triple-echo fat fraction (mean 2.9 ± 1.4%) in healthy children (<i>p</i> = 0.010).</p

Bland-Altman plots for measurement of hepatic fat fraction using dual and triple-echo MRI.

<p>Bland-Altman plots demonstrated good agreement between dual and triple-echo fat fractions.</p

Correlation between clinical and laboratory findings and hepatic fat fraction in dual- and triple-echo fat quantification MRI.

<p>*from Spearman’s correlation test</p><p>Correlation between clinical and laboratory findings and hepatic fat fraction in dual- and triple-echo fat quantification MRI.</p

LIGHT (TNFSF14) Increases the Survival and Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells

<div><p>LIGHT (HVEM-L, TNFSF14, or CD258), an entity homologous to <u>l</u>ymphotoxins, with <u>i</u>nducible nature and the ability to compete with herpes simplex virus <u>g</u>lycoprotein D for <u>h</u>erpes virus entry mediator (HVEM)/<u>t</u>umor necrosis factor (TNF)-related 2, is a member of the TNF superfamily. It is expressed as a homotrimer on activated T cells and dendritic cells (DCs), and has three receptors: HVEM, LT-β receptor (LTβR), and decoy receptor 3 (DcR3). So far, three receptors with distinct cellular expression patterns are known to interact with LIGHT. Follicular DCs and stromal cells bind LIGHT through LTβR. We monitored the effects of LIGHT on human bone marrow-derived mesenchymal stem cells (BM-MSCs). At first, we checked the negative and positive differentiation markers of BM-MSCs. And we confirmed the quality of MSCs by staining cells undergoing adipogenesis (Oil Red O staining), chondrogenesis (Alcian blue staining), and osteogenesis (Alizarin red staining). After rhLIGHT treatment, we monitored the count, viability, and proliferation of cells and cell cycle distribution. PDGF and TGFβ production by rhLIGHT was examined by ELISA, and the underlying biological mechanisms were studied by immunoblotting by rhLIGHT treatment. LTβR was constitutively expressed on the surface of human BM-MSCs. Cell number and viability increased after rhLIGHT treatment. BM-MSC proliferation was induced by an increase in the S/G₂/M phase. The expression of not only diverse cyclins such as cyclin B1, D1, D3, and E, but also CDK1 and CDK2, increased, while that of p27 decreased, after rhLIGHT treatment. RhLIGHT-induced PDGF and TGFβ production mediated by STAT3 and Smad3 activation accelerated BM-MSC proliferation. Thus, LIGHT and LTβR interaction increases the survival and proliferation of human BM-MSCs, and therefore, LIGHT might play an important role in stem cell therapy.</p></div