The Effects of Mechanical Stress on the Growth, Differentiation, and Paracrine Factor Production of Cardiac Stem Cells

Stem cell therapies have been clinically employed to repair the injured heart, and cardiac stem cells are thought to be one of the most potent stem cell candidates. The beating heart is characterized by dynamic mechanical stresses, which may have a significant impact on stem cell therapy. The purpose of this study is to investigate how mechanical stress affects the growth and differentiation of cardiac stem cells and their release of paracrine factors. In this study, human cardiac stem cells were seeded in a silicon chamber and mechanical stress was then induced by cyclic stretch stimulation (60 cycles/min with 120% elongation). Cells grown in non-stretched silicon chambers were used as controls. Our result revealed that mechanical stretching significantly reduced the total number of surviving cells, decreased Ki-67-positive cells, and increased TUNEL-positive cells in the stretched group 24 hrs after stretching, as compared to the control group. Interestingly, mechanical stretching significantly increased the release of the inflammatory cytokines IL-6 and IL-1β as well as the angiogenic growth factors VEGF and bFGF from the cells in 12 hrs. Furthermore, mechanical stretching significantly reduced the percentage of c-kit-positive stem cells, but increased the expressions of cardiac troponin-I and smooth muscle actin in cells 3 days after stretching. Using a traditional stretching model, we demonstrated that mechanical stress suppressed the growth and proliferation of cardiac stem cells, enhanced their release of inflammatory cytokines and angiogenic factors, and improved their myogenic differentiation. The development of this in vitro approach may help elucidate the complex mechanisms of stem cell therapy for heart failure

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Volatile Organic Compound Sensing with WO₃‑Based Gas Sensors: Surface Chemistry Basics

The sensing properties of WO3-based gas sensors were evaluated at an operating temperature of 150 °C in the presence of different volatile organic compounds (VOCs). Simultaneously to the sensing tests, operando diffuse-reflectance infrared Fourier transform spectra were acquired. Remarkably, no CO2 generation was observed under gas exposure for any of the target VOCs. Catalytic combustion properties of the WO3 toward acetone and ethanol at temperatures from 150 to 400 °C, both in dry and humid atmospheres, were additionally performed. Such measurements confirmed that no combustion occurred for ethanol (up to at least 300 °C) while it became detectable for acetone only starting from 250 °C. The reaction products are acetaldehyde and acetate in the case of ethanol exposure and acetate and formate in the case of acetone exposure. The oxidation catalytic effect of WO3 was confirmed for both toluene, where benzaldehyde and benzoate modes were observed, and acetylene (where acetaldehyde and ethenol were detected). The systematic absence of CO2 as a product and the identification of oxidized species are the basis of the proposed reaction mechanisms

Morphological changes and cell survival.

<p><b>A</b>) The cells of both groups showed similar density and morphology at baseline. However, when compared to static culture, stretching stimulation decreased the cell density and caused the cells to be arranged parallel to the stretch direction after 24 hrs and 3 days of culture (bar = 100 µm). <b>B</b>) The number of surviving cells was significantly less at 24 hrs and 3 days when the cells were cultured under stretching stimulation compared to under static condition.</p

Expression of stem cell and differentiation markers.

<p>Immunostaining analyses were used to observe the expression of markers for stem cells (c-kit⁺, <b>A</b>), cardiomyocytes (troponin-I⁺ cells, <b>B</b>), smooth muscle cells (SMA⁺ cells, <b>C</b>), or endothelial cells (CD31⁺ cells, <b>D</b>) after 3 days of culture. Representative images of immunostaining are shown in the upper panels. Nuclei were labeled with DAPI. Scale bars represent 100 µm. Quantitative data were derived from six separate experiments using different cells.</p

Morphological observation of cells under scanning electron microscopy.

<p>Cells in the stretch group were more likely to display a spindle shape, in contrast to the flat shape typically observed in the static group.</p

Experimental designs and time schedule of assessments.

<p>The cells were seeded at a density of 1×10⁵/chamber. After 24 hrs for manipulation, the chambers were continuously stretched at a frequency of 60 cycles/min with 120% elongation (stretch group). Non-stretched chambers were used as controls (static group). Assessments were performed at the indicated time points.</p

Cell proliferation and apoptosis.

<p>The upper panels show representative images of immunostaining for proliferating cells (Ki67-positive, <b>A</b>) and apoptotic (TUNEL, <b>B</b>) cells. Nuclei were labeled with DAPI. Quantitative analysis showed a significant decrease in the number of proliferative cells (<b>A</b>, lower panel) and a significant increase in the number of apoptotic cells (<b>B</b>, lower panel) in the stretch group compared with the static group. Data represent 4 separate experiments using different cells.</p

ELISA analysis of cytokines and growth factors released from CDCs.

<p>The concentrations of the angiogenic factors, VEGF (<b>A</b>) and bFGF (<b>B</b>), in conditioned media were significantly higher in the stretch group than the static group. The concentrations of the inflammatory cytokines, IL-6 (<b>C</b>) and IL-1β (<b>D</b>), were also significantly higher in the stretch group than the static group. In contrast, the concentrations of IGF-1 (<b>E</b>), HGF (<b>F</b>), SDF-1α (<b>G</b>), and TGF-β₁ (<b>H</b>) were not significantly different between the groups. Data represent 6 separate experiments using different cells.</p