Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called "organ-on-a-chip" technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field.

• MeSH
• Models, Biological * MeSH
• Biomedical Research MeSH
• Tissue Array Analysis * MeSH
• Humans MeSH
• Micro-Electrical-Mechanical Systems MeSH
• Microfluidic Analytical Techniques * MeSH
• Mice MeSH
• Tissue Engineering * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Interactions between a micro-magnet array and living cells may guide the establishment of cell networks due to the cellular response to a magnetic field. To manipulate mesenchymal stem cells free of magnetic nanoparticles by a high magnetic field gradient, we used high quality micro-patterned NdFeB films around which the stray field's value and direction drastically change across the cell body. Such micro-magnet arrays coated with parylene produce high magnetic field gradients that affect the cells in two main ways: i) causing cell migration and adherence to a covered magnetic surface and ii) elongating the cells in the directions parallel to the edges of the micro-magnet. To explain these effects, three putative mechanisms that incorporate both physical and biological factors influencing the cells are suggested. It is shown that the static high magnetic field gradient generated by the micro-magnet arrays are capable of assisting cell migration to those areas with the strongest magnetic field gradient, thereby allowing the build up of tunable interconnected stem cell networks, which is an elegant route for tissue engineering and regenerative medicine.

• MeSH
• Cell Adhesion MeSH
• Time Factors MeSH
• Tissue Array Analysis methods   MeSH
• Rats MeSH
• Culture Media chemistry   MeSH
• Magnetic Fields MeSH
• Magnets * MeSH
• Mesenchymal Stem Cells cytology   MeSH
• Nanoparticles MeSH
• Cell Movement MeSH
• Rats, Wistar MeSH
• Cell Survival MeSH
• Ferric Compounds chemistry   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

MicroRNAs (miRNAs), important regulators of cellular processes, show specific expression signatures in different blood cell lineages and stages of hematopoietic stem cell (HSC) differentiation, indicating their role in the control of hematopoiesis. Because neonatal blood displays various features of immaturity, we might expect differential miRNA regulation. Herein, we determined miRNA expression profiles of umbilical cord blood (UCB) cell lineages and compared them to those of bone marrow (BM) and peripheral blood (PB) cell counterparts. Further, we determined mRNA expression profiles using whole-genome microarrays. An approach combining bioinformatic prediction of miRNA targets with mRNA expression profiling was used to search for putative targets of miRNAs with potential functions in UCB. We pointed out several differentially expressed miRNAs and associated their expression with the target transcript levels. miR-148a expression was suppressed in HSCs and its level inversely correlated with the previously verified target, DNA methyltransferase 3B, suggesting dependence of de novo DNA methylation in HSCs on miR-148a. Prolonged cell survival of UCB HSCs may be associated with low expression of miR-143 and miR-145 and up-regulation of their downstream targets (high expression of c-MYC and miR-17-92 and following repression of TGFBR2). In HSCs, we monitored significant up-regulation of eight miRNAs, which were previously verified as regulators of HOX genes. Further, miR-146b may be associated with immaturity of neonatal immune system because it is strongly up-regulated in UCB granulocytes and T lymphocytes compared to PB cell counterparts. Comparative analysis revealed 13 miRNAs significantly altered between UCB and BM CD34(+) cells. In UCB CD34(+) cells, we monitored up-regulation of miR-520h, promoting differentiation of HSCs into progenitor cells, and reduction of miR-214, whose expression might support HSC survival. In conclusion, UCB cells show specific miRNA expression patterns, indicating different regulation in these cells.

• MeSH
• Antigens, CD34 metabolism   MeSH
• Cell Lineage genetics   MeSH
• Adult MeSH
• Fetal Blood cytology   metabolism   MeSH
• Hematopoietic Stem Cells metabolism   MeSH
• Blood Cells metabolism   physiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• MicroRNAs genetics   metabolism   MeSH
• Infant, Newborn MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Aged MeSH
• Cluster Analysis MeSH
• Gene Expression Profiling MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Validation Study MeSH

Post-transcriptional control of mRNA by micro-RNAs (miRNAs) represents an important mechanism of gene regulation. miRNAs act by binding to the 3' untranslated region (3'UTR) of an mRNA, affecting the stability and translation of the target mRNA. Here, we present a numerical model of miRNA-mediated mRNA downregulation and its application to analysis of temporal microarray data of HepG2 cells transfected with miRNA-124a. Using the model our analysis revealed a novel mechanism of mRNA accumulation control by miRNA, predicting that specific mRNAs are controlled in a digital, switch-like manner. Specifically, the contribution of miRNAs to mRNA degradation is switched from maximum to zero in a very short period of time. Such behaviour suggests a model of control in which mRNA is at a certain moment protected from binding of miRNA and further accumulates with a basal rate. Genes associated with this process were identified and parameters of the model for all miRNA-124a affected mRNAs were computed.

• MeSH
• Cell Line MeSH
• Down-Regulation MeSH
• Humans MeSH
• RNA, Messenger metabolism   MeSH
• MicroRNAs metabolism   MeSH
• Models, Genetic MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• RNA Stability MeSH
• Gene Silencing MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Early Diagnosis MeSH
• Molecular Diagnostic Techniques MeSH
• Gene Expression MeSH
• Genome, Human MeSH
• Humans MeSH
• RNA, Messenger analysis   MeSH
• MicroRNAs analysis   MeSH
• Polymerase Chain Reaction MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Gene Expression Profiling MeSH
• Check Tag
• Humans MeSH
• Publication type
• Book Review MeSH

OBJECTIVES: MicroRNAs (miRNAs) play key roles in a wide variety of normal and pathological cellular processes. A number of studies identified hematopoietic-specific miRNAs that are necessary for correct function of blood cells. Out of our microarray data, we chose 13 miRNAs that showed differential expression in peripheral blood cells (miR-15b, miR-16, miR-24, miR-30c, miR-106b, miR-142-3p, miR-142-5p, miR-150, miR-155, miR-181, miR-223, miR-342, and miR-451) and examined their expression in separated hematopoietic cell lineages. METHODS: Using quantitative real-time polymerase chain reaction, we measured relative expression of the miRNAs in fractions of reticulocytes, platelets, granulocytes, monocytes, B- and T-lymphocytes as well as in several hematopoietic cell lines. RESULTS: We observed that miR-16 and miR-142-3p were highly expressed in all native cell lineages, miR-451 reached the maximal expression in reticulocytes, miR-223 in platelets, granulocytes and monocytes, and miR-150 in B- and T-lymphocytes. Hierarchical clustering analysis grouped the lineage samples according to their origin based on the expression of these miRNAs. To validate discrimination power of the miRNAs, we quantified expression of the 13 miRNAs in several immortalized cell lines. Although the cell lines showed miRNA expression patterns considerably different from those of native cell lineages, clustering analysis distinguished between myeloid, lymphoid and non-hematopoietic cells. CONCLUSIONS: In conclusion, the study reports the expression levels of 13 miRNAs in particular blood cell lineages as well as immortalized cell lines. We demonstrate that the expression profiles of these miRNAs may be used for discrimination of the hematopoietic cell lineages.

• MeSH
• Cell Differentiation physiology   MeSH
• K562 Cells MeSH
• Financing, Organized MeSH
• HeLa Cells MeSH
• Leukocytes cytology   metabolism   MeSH
• Humans MeSH
• Lymphoid Progenitor Cells cytology   metabolism   MeSH
• MicroRNAs biosynthesis   MeSH
• Granulocyte Precursor Cells cytology   metabolism   MeSH
• Gene Expression Regulation physiology   MeSH
• Reticulocytes cytology   metabolism   MeSH
• Oligonucleotide Array Sequence Analysis methods   MeSH
• Gene Expression Profiling methods   MeSH
• Blood Platelets cytology   metabolism   MeSH
• Check Tag
• Humans MeSH

Serrated adenocarcinoma (SAC) and colorectal carcinomas showing histological and molecular features of high-level of microsatellite instability (hmMSI-H) are both end points of the serrated pathway of colorectal carcinogenesis. Despite common features (right-sided location, CpG island methylation phenotype and BRAF mutation) there are no studies comparing the microRNA (miRNA) expression profiles in SACs and hmMSI-H. The microtranscriptome from 12 SACs and 8 hmMSI-H were analysed using Affymetrix GeneChip miRNA 3.0 arrays and differentially enriched functions involving immune response were observed from this comparison. miR-181a-2* was found significantly more expressed in hmMSI-H than in SAC and higher expression of this miRNA in microsatellite unstable colorectal cancer were corroborated by Real-Time PCR in an extended series (61 SAC, 21 hmMSI-H). An analysis of genes possibly regulated by miR-181a-2* was carried out and, amongst these, an inverse correlation of NAMPT with miR-181a-2* expression was observed, whereas, for TRAF1 and SALL1, additional regulation mechanisms involving CpG island methylation were observed. miR-181a-2* is associated with particular histological and molecular features of colorectal carcinomas within the serrated pathological pathway and might play a role in the immune responses of microsatellite instability carcinomas.

• MeSH
• CpG Islands MeSH
• Cytokines genetics   metabolism   MeSH
• TNF Receptor-Associated Factor 1 genetics   metabolism   MeSH
• Gene Ontology MeSH
• Carcinoma genetics   metabolism   physiopathology   MeSH
• Colorectal Neoplasms genetics   metabolism   physiopathology   MeSH
• Humans MeSH
• DNA Methylation MeSH
• MicroRNAs genetics   metabolism   MeSH
• Microsatellite Instability * MeSH
• Cell Line, Tumor MeSH
• Nicotinamide Phosphoribosyltransferase genetics   metabolism   MeSH
• Gene Expression Regulation, Neoplastic genetics   MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Aged MeSH
• Transcription Factors genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Our aim was to identify miRNAs that can predict risk of relapse in pediatric patients with acute lymphoblastic leukemia (ALL). Following high-throughput miRNA expression analysis (48 samples), five miRs were selected for further confirmation performed by real time quantitative PCR on a cohort of precursor B-cell ALL patients (n = 138). The results were correlated with clinical parameters and outcome. Low expression of miR-151-5p, and miR-451, and high expression of miR-1290 or a combination of all three predicted inferior relapse free survival (P = 0.007, 0.042, 0.025, and <0.0001, respectively). Cox regression analysis identified aberrant expression of the three miRs as an independent prognostic marker with a 10.5-fold increased risk of relapse (P = 0.041) in PCR-MRD non-high risk patients. Furthermore, following exclusion of patients harboring IKZF1 deletion, the aberrant expression of all three miRs could identify patients with a 24.5-fold increased risk to relapse (P < 0.0001). The prognostic relevance of the three miRNAs was evaluated in a non-BFM treated precursor B-cell ALL cohort (n = 33). A significant correlation between an aberrant expression of at least one of the three miRs and poor outcome was maintained (P < 0.0001). Our results identify an expression profile of miR-151-5p, miR-451, and miR-1290 as a novel biomarker for outcome in pediatric precursor B-cell ALL patients, regardless of treatment protocol. The use of these markers may lead to improved risk stratification at diagnosis and allow early therapeutic interventions in an attempt to improve survival of high risk patients.

• MeSH
• Child MeSH
• Cohort Studies MeSH
• Infant MeSH
• Humans MeSH
• MicroRNAs biosynthesis   genetics   MeSH
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis   genetics   physiopathology   MeSH
• Child, Preschool MeSH
• Prognosis MeSH
• Recurrence MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Gene Expression Profiling MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH