Identifying a molecular phenotype for bone marrow stromal cells with in vivo bone-forming capacity

The ability of bone marrow stromal cells (BMSCs) to differentiate into osteoblasts is being exploited in cell-based therapy for repair of bone defects. However, the phenotype of ex vivo cultured BMSCs predicting their bone-forming capacity is not known. Thus we employed DNA microarrays comparing two human bone marrow stromal cell (hBMSC) populations: One is capable of in vivo heterotopic bone formation (hBMSC-TERT(+Bone)), and the other is not (hBMSC-TERT(-Bone)). Compared with hBMSC-TERT(-Bone), the hBMSC-TERT(+Bone) cells had an increased overrepresentation of extracellular matrix genes (17% versus 5%) and a larger percentage of genes with predicted SP3 transcription factor-binding sites in their promoter region (21% versus 8%). On the other hand, hBMSC-TERT(-Bone) cells expressed a larger number of immune-response-related genes (26% versus 8%). In order to test for the predictive value of these markers, we studied the correlation between their expression levels in six different hBMSC-derived clones and the ability to form bone in vivo. We found a significant correlation for decorin, lysyl oxidase-like 4, natriuretic peptide receptor C, and tetranectin. No significant positive correlation was found for canonical osteoblastic markers Runx2, alkaline phosphatase, collagen type I, osteopontin, and bone sialoprotein. Prospective isolation of four additional hBMSC clones based on their expression levels of the molecular markers correlated with their in vivo bone-formation ability. In conclusion, our data suggest an in vitro molecular signature predictive for hBMSCs' in vivo bone-formation ability. Identifying more of these predictive markers would be very useful in the quality control of osteoblastic cells before use in therapy

A simple and reliable protocol for long-term culture of murine bone marrow stromal (mesenchymal) stem cells that retained their in vitro and in vivo stemness in long-term culture

Table S1. List of primers used for qRT-PCR. Table S2. Full osteogenic gene expression list (total 84 genes) by BMSCs-FS (p25) versus ST2 cells during osteoblast differentiation including all significant/non-significant pathways. (DOCX 20 kb

Perception SoC based on an ultrasonic array of sensors : efficient DSP core implementation and subsequent experimental results

We are concerned with the design, implementation, and validation of a perception SoC based on an ultrasonic array of sensors. The proposed SoC is dedicated to ultrasonic echography applications. A rapid prototyping platform is used to implement and validate the new architecture of the digital signal processing (DSP) core. The proposed DSP core efficiently integrates all of the necessary ultrasonic B-mode processing modules. It includes digital beamforming, quadrature demodulation of RF signals, digital filtering, and envelope detection of the received signals. This system handles 128 scan lines and 6400 samples per scan line with a angle of view span. The design uses a minimum size lookup memory to store the initial scan information. Rapid prototyping using an ARM/FPGA combination is used to validate the operation of the described system. This system offers significant advantages of portability and a rapid time to market

Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer

Despite recent advances in cancer management, colorectal cancer (CRC) remains the third most common cancer and a major health-care problem worldwide. MicroRNAs have recently emerged as key regulators of cancer development and progression by targeting multiple cancer-related genes; however, such regulatory networks are not well characterized in CRC. Thus, the aim of this study was to perform global messenger RNA (mRNA) and microRNA expression profiling in the same CRC samples and adjacent normal tissues and to identify potential miRNA-mRNA regulatory networks. Our data revealed 1273 significantly upregulated and 1902 downregulated genes in CRC. Pathway analysis revealed significant enrichment in cell cycle, integrated cancer, Wnt (wingless-type MMTV integration site family member), matrix metalloproteinase, and TGF-β pathways in CRC. Pharmacological inhibition of Wnt (using XAV939 or IWP-2) or TGF-β (using SB-431542) pathways led to dose- and time-dependent inhibition of CRC cell growth. Similarly, our data revealed up- (42) and downregulated (61) microRNAs in the same matched samples. Using target prediction and bioinformatics, ~77% of the upregulated genes were predicted to be targeted by microRNAs found to be downregulated in CRC. We subsequently focused on EZH2 (enhancer of zeste homolog 2 ), which was found to be regulated by hsa-miR-26a-5p and several members of the let-7 (lethal-7) family in CRC. Significant inverse correlation between EZH2 and hsa-miR-26a-5p (R(2)=0.56, P=0.0001) and hsa-let-7b-5p (R(2)=0.19, P=0.02) expression was observed in the same samples, corroborating the belief of EZH2 being a bona fide target for these two miRNAs in CRC. Pharmacological inhibition of EZH2 led to significant reduction in trimethylated histone H3 on lysine 27 (H3K27) methylation, marked reduction in cell proliferation, and migration in vitro. Concordantly, small interfering RNA-mediated knockdown of EZH2 led to similar effects on CRC cell growth in vitro. Therefore, our data have revealed several hundred potential miRNA-mRNA regulatory networks in CRC and suggest targeting relevant networks as potential therapeutic strategy for CRC

Bidirectional parallel capacitive data links: Modeling and experimental results

ABSTRACT: We present, in this paper, a bidirectional capacitive data link. Enhancement of the spatial pulse position modulation used on the downlink is introduced, and a load-shift keying modulation is implemented for the uplink. Different grounds on the transmitter and the receiver are discussed, and a compatible solution is proposed. A human skin electrical model is extracted using the agilent impedance analyzer 4294A while doing in vivo measurements on cheek skin and then applying curve fitting to the data between 2 and 20 MHz. Multiple geometries for the link are analyzed, and a 5-mm × 5-mm plate size is used for the design of the transceiver. The signal-to-noise ratio along with the capacity of the channel is analyzed theoretically while computing the limits for the downlink and the valid operating frequency to highlight the core parameters that affect the crosstalk interference between channels. The tradeoff in using the uplink on the same channel as the downlink is also discussed and analyzed. The operating frequency is 10 MHz, a bit-rate of 20 Mb/s is demonstrated on the uplink, and 10 Mb/s is demonstrated on the downlink. An in vivo human skin model for a 5-mm × 5-mm plate size with 21.2-mm separation is extracted, and the capacity's equation of the channel is computed using the equations for the analysis of the system