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

Downregulation of VEGFA inhibits proliferation, promotes apoptosis, and suppresses migration and invasion of renal clear cell carcinoma

Fan-Chang Zeng,1,2 Ming-Qiang Zeng,1 Liang Huang,1 Yong-Lin Li,1 Ben-Min Gao,1 Jun-Jie Chen,1 Rui-Zhi Xue,1 Zheng-Yan Tang1 1Department of Urology, Xiangya Hospital, Central South University, Changsha, 2Department of Urology, Hainan General Hospital, Haikou, People’s Republic of China Objective: The aim of this study was to investigate the effects of vascular endothelial growth factor A (VEGFA) on cell proliferation, apoptosis, migration, and invasion in renal clear cell carcinoma (RCCC). Methods: Between June 2012 and June 2015, RCCC tissues were obtained for the experimental group, and RCCC adjacent tumor-free kidney parenchyma tissues were obtained for the control group. VEGFA mRNA and protein expressions and phosphoinositide 3-kinase, serine/threonine-specific protein kinase (AKT), and phosphorylated-AKT protein expressions were detected. The chemically synthesized specific siRNA using RNA interference technology was used to inhibit VEGFA gene expression in human RCCC 786-O cells. The negative control (NC) group was transfected with NC sequence, and the blank group was transfected with no sequence. Flow cytometry, scratch test, and cell-penetrating experiment were used to detect cell proliferation, apoptosis, migration, and invasion of 786-O cells. Results: Positive expression of VEGFA protein was 60.62% in RCCC tissue and 18.34% in adjacent tissue with statistically significant difference (P<0.001). VEGFA protein and mRNA expressions were higher in RCCC tissue than those in adjacent tissue (both P<0.01). VEGF expression in RCCC tissue was associated with Fuhrman grading and American Joint Committee on Cancer staging (both P<0.05). After RCCC 786-O cells transfecting the VEGFA siRNA, the VEGFA mRNA and protein expressions and phosphoinositide 3-kinase and phosphorylated-AKT protein expressions were significantly decreased, cell proliferation was remarkably inhibited, cell apoptotic ratio was obviously increased, and migration distance and invasive cell number were markedly decreased compared to those in the NC group and the blank group (all P<0.05). Conclusion: Inhibition of VEGFA inhibited proliferation, promoted apoptosis, and suppressed migration and invasion of RCCC 786-O cells. VEGF has a potential role in diagnosis and therapy of RCCC. Keywords: 786-O, siRNA, transfection, cell biological behavior, PI3K/AKT, Fuhrman grading, AJCC staging, HK-

Functionalized anodic aluminum oxide (AAO) membranes for affinity protein separation

National Nature Science Foundation of China [30500127]; Natural Science Foundation of Fujian Province [C0510005]An ideal affinity membrane should own well uniformities. However, most existing microporous membranes used as affinity matrices generally have wide pore size distribution and some thickness variation. In this paper, chitosan (CS)-anodic aluminum oxide (AAO) composite membrane with excellent uniformities, such as narrow pore size and porosity distribution, as well as uniform membrane thickness, was fabricated. for the first time. Cu(2+)-attached affinity membrane was obtained by immobilizing Cu(2+) on the CS-AAO membrane. The contents of CS and Cu(2+) of affinity membranes were similar to 49.7 and 27.15 mg/g membrane. respectively. The Cu(2+)-attached affinity membranes were used to recover a model protein, hemoglobin, from hemoglobin-phosphate solution (batch manner) and from the hemolysate (dynamic manner). The protein adsorption indicated that the adsorption capacity of hemoglobin was similar to 17.5 mg/g membrane, and the adsorption isotherm fitted the Freundlich model well. Elution of protein showed desorption ratio was up to 91.2% using 0.5 M imidazole aqueous solution as the desorption agent. The adsorption capacities of all the tested affinity membranes did not significantly change during the repeated adsorption-desorption operations. The result of dynamic experiment showed Cu(2+)-attached affinity membranes can well purify the hemoglobin from the red cell lysate. (C) 2008 Elsevier B.V. All rights reserved

Synthesis and characterization of β-diketiminate lanthanide complexes: the effect of the bulkiness of ancillary ligand on the reaction

The reactions of ytterbium dichlorides with different β-diketiminate ligand ((Ar)NC(Me)CHC(Me)N(Ar′), Ar=Ar′=C6H5 (L1); Ar=Ar′=2,6-Me2-C6H3 (L2); Ar=C6H5, ) with 1 equiv of Cp′Na were studied. It was found that the bulkiness of β-diketiminate ligand and cyclopentadienyl group both have significant effect on the above reaction. For less bulky ligands L1 and L2, the reaction affords not the expected mixed-ligand ytterbium chloride, (C5H5)YbLCl or (CH3C5H4)YbCl, but the ligand-redistributed product (C5H5)2YbL or (CH3C5H4)2YbL. For bulkier ligand L3, the desired anionic ytterbium chloride (C5H5)YbL3(μ-Cl)2Li(THF)2 is obtained. For the smallest ligand L1, the expected ytterbium monochloride can also be obtained using bulky C5Me5Na as reactant. Each of these complexes was well characterized, while several have been characterized by X-ray diffraction structure determination

Synthesis of Mn doping Ag-In-Zn-S nanoparticles and their photoluminescence properties

Mn doped Ag-In-Zn-S nanoparticles (Mn:AgInZnS) were successfully synthesized by using a practical hot-injection method. The as-prepared Mn: AgInZnS nanoparticles were triangular shape with average radius of 6(+/- 0.5) nm, and the composition of doped Mn was about 7.29 by wt.%. Moreover, the Mn:AgInZnS nanoparticles demonstrated strong and stable photoluminescence emission at about 620 nm, and the UV-vis absorption spectrum further revealed band gap absorption around 600 nm. Furthermore, the photoluminescence lifetime of Mn:AgInZnS nanoparticles was about 1.38 mu s which indicated the tremendous potential applications in cell labelings, fluorescent imaging, solar cells and LEDs. (C) 2015 Elsevier Ltd. All rights reserved