Allogeneic cardiospheres increase viable myocardium, decrease scar, improve function, and attenuate adverse remodeling in the infarcted rat heart, without deleterious immunological sequelae. These observations lay the groundwork for developing cardiospheres as a novel off-the-shelf microtissue product for myocardial regeneration.

The pluripotency of human embryonic stem cells (hESC) could have great potential for the development of cell replacement therapies. Previous studies have converged on the finding that OCT4, SOX2, and NANOG serve as key regulators in the maintenance of hESC. However, other signals that regulate hESC maintenance remain poorly studied. Here we describe a novel role of an RNA polymerase III (Pol III) subunit, POLR3G, in the maintenance of pluripotency in hESC. We demonstrate the presence of POLR3G in undifferentiated hESC, human induced pluripotent stem cells (hiPSC), and early mouse blastocysts. Downregulation of POLR3G is observed on differentiation of hESC and hiPSC, suggesting that POLR3G can be used as a molecular marker to readily identify undifferentiated pluripotent stem cells from their differentiated derivatives. Using an inducible shRNA lentiviral system, we found evidence that decreased levels of POLR3G result in loss of pluripotency and promote differentiation of hESC to all three germ layers but have no effect on cell apoptosis. On the other hand, overexpression of POLR3G has no effect on pluripotency and apoptosis in undifferentiated hESC. Interestingly, hESC expressing elevated levels of POLR3G are more resistant to differentiation. Furthermore, our experimental results show that POLR3G is a downstream target of OCT4 and NANOG, and our pharmacological study indicated that POLR3G expression can be readily regulated by the Erk1/2 signaling pathway. This study is the first to show an important role of POLR3G in the maintenance of hESC, suggesting a potential role of Pol III transcription in regulating hESC pluripotency. STEM CELLS

Taxanes are widely employed chemotherapies for patients with metastatic prostate and breast cancer. Here, we show that loss of Diaphanous-related formin-3 (DIAPH3), frequently associated with metastatic breast and prostate cancers, correlates with increased sensitivity to taxanes. DIAPH3 interacted with microtubules (MT), and its loss altered several parameters of MT dynamics as well as decreased polarized force generation, contractility, and response to substrate stiffness. Silencing of DIAPH3 increased the cytotoxic response to taxanes in prostate and breast cancer cell lines. Analysis of drug activity for tubulin-targeted agents in the NCI-60 cell line panel revealed a uniform positive correlation between reduced DIAPH3 expression and drug sensitivity. Low DIAPH3 expression correlated with improved relapse-free survival in breast cancer patients treated with chemotherapeutic regimens containing taxanes. Our results suggest that inhibition of MT stability arising from DIAPH3 downregulation enhances susceptibility to MT poisons, and that the DIAPH3 network potentially reports taxane sensitivity in human tumors.

The limited clinical success of anti‐HGF/MET drugs can be attributed to the lack of predictive biomarkers that adequately select patients for treatment. We demonstrate here that quantitative digital imaging of formalin fixed paraffin embedded tissues stained by immunohistochemistry can be used to measure signals from weakly staining antibodies and provides new opportunities to develop assays for detection of MET receptor activity. To establish a biomarker panel of MET activation, we employed seven antibodies measuring protein expression in the HGF/MET pathway in 20 cases and up to 80 cores from 18 human cancer types. The antibodies bind to epitopes in the extra (EC)‐ and intracellular (IC) domains of MET (MET4EC, SP44_METIC, D1C2_METIC), to MET‐pY1234/pY1235, a marker of MET kinase activation, as well as to HGF, pSFK or pMAPK. Expression of HGF was determined in tumour cells (T_HGF) as well as in stroma surrounding cancer (St_HGF). Remarkably, MET4EC correlated more strongly with pMET (r = 0.47) than SP44_METIC (r = 0.21) or D1C2_METIC (r = 0.08) across 18 cancer types. In addition, correlation coefficients of pMET and T_HGF (r = 0.38) and pMET and pSFK (r = 0.56) were high. Prediction models of MET activation reveal cancer‐type specific differences in performance of MET4EC, SP44_METIC and anti‐HGF antibodies. Thus, we conclude that assays to predict the response to HGF/MET inhibitors require a cancer‐type specific antibody selection and should be developed in those cancer types in which they are employed clinically.