The vascular stem cell niche

Stem cells in adult organs reside in specialized niches that regulate their proliferation and differentiation. Investigations during the last few years have unveiled a regulatory role for blood vessels in these microenvironments. Mesenchymal stem cells (MSCs) are located surrounding capillaries in a variety of tissues and have the capacity to differentiate into different mesodermal lineages. Angiogenic progenitor cells have also been found in the adventitial layer of large vessels. In the bone marrow, endothelial cells control hematopoietic stem cell (HSC) release, and in the brain, blood vessels regulate neural stem cell (NSC) self-renewal and neurogenesis. Similarly, perivascular progenitor cells have also been found in the heart. This intimate connection between stem cells and the vasculature contributes to tissue homeostasis and repair. In this review, we focus on the regulation of stem and progenitor cells in different adult niches by blood vessels and the few mechanisms that are known to mediate this interaction.S

Optimized CUBIC protocol for three-dimensional imaging of chicken embryos at single-cell resolution

The CUBIC tissue-clearing protocol has been optimized to produce translucent immunostained whole chicken embryos and embryo brains. When combined with multispectral light-sheet microscopy, the validated protocol presented here provides a rapid, inexpensive and reliable method for acquiring accurate histological images that preserve three-dimensional structural relationships with single-cell resolution in whole early-stage chicken embryos and in the whole brains of late-stage embryos.The study was supported by the Human Frontier Science Program (RGP0004/2013), the European Commission Seventh Framework Programme (FP7, EU CIG Grant), the Ministerio de Economı́a y Competitividad (FIS2013-41802-R) and Consejerı́a de Educación, Juventud y Deporte, Comunidad de Madrid (P2013/ICE 2958)

Assessment of myocardial viscoelasticity with Brillouin spectroscopy in myocardial infarction and aortic stenosis models.

Heart diseases are associated with changes in the biomechanical properties of the myocardial wall. However, there is no modality available to assess myocardial stiffness directly. Brillouin microspectroscopy (mBS) is a consolidated mechanical characterization technique, applied to the study of the viscoelastic and elastic behavior of biological samples and may be a valuable tool for assessing the viscoelastic properties of the cardiac tissue. In this work, viscosity and elasticity were assessed using mBS in heart samples obtained from healthy and unhealthy mice (n = 6 per group). Speckle-tracking echocardiography (STE) was performed to evaluate heart deformation. We found that mBS was able to detect changes in stiffness in the ventricles in healthy myocardium. The right ventricle showed reduced stiffness, in agreement with its increased compliance. mBS measurements correlated strongly with STE data, highlighting the association between displacement and stiffness in myocardial regions. This correlation was lost in pathological conditions studied. The scar region in the infarcted heart presented changes in stiffness when compared to the rest of the heart, and the hypertrophied left ventricle showed increased stiffness following aortic stenosis, compared to the right ventricle. We demonstrate that mBS can be applied to determine myocardial stiffness, that measurements correlate with functional parameters and that they change with disease.post-print6652 K

Visualization 2: Looking inside the heart: a see-through view of the vascular tree

Visualization 2. 3D imaging of the vasculature obtained with SPIM following perfusion with FITC-labelled lectin Originally published in Biomedical Optics Express on 01 June 2017 (boe-8-6-3110

Visualization 1: Looking inside the heart: a see-through view of the vascular tree

Visualization 1. 3D imaging of the vasculature obtained with SPIM following anti-CD31 labelling Originally published in Biomedical Optics Express on 01 June 2017 (boe-8-6-3110

The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression

Hepatocellular carcinoma is strongly associated with chronic infection by the hepatitis B virus (HBV) and has poor prognosis due to intrahepatic metastasis. HBx is often the only HBV protein detected in hepatic tumor cells; however, its contribution to tumor invasion and metastasis has not been established so far. In this work, we show that HBx enhances tumor cell invasion, both in vivo and in vitro. The increased invasive capacity induced by HBx is mediated by an upregulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) expression, which in turn activates matrix metalloproteinase-2. Induction of both MT1-MMP expression and cell invasion by HBx is dependent on cyclooxygenase-2 (COX-2) activity. In addition, HBx upregulates the expression of COX-2, which is mediated by the transcriptional activation of the COX-2 gene promoter in a nuclear factor of activated T cell–dependent (NF-AT–dependent) manner. These results demonstrate the ability of HBx to promote tumor cell invasion by a mechanism involving the upregulation of MT1-MMP and COX-2 and provide new insights into the mechanism of action of this viral protein and its involvement in tumor metastasis and recurrence of hepatocellular carcinoma

New Frontiers in Colorectal Cancer Treatment Combining Nanotechnology with Photo- and Radiotherapy

Colorectal cancer is the third most common cancer worldwide. Despite recent advances in the treatment of this pathology, which include a personalized approach using radio- and chemotherapies in combination with advanced surgical techniques, it is imperative to enhance the performance of these treatments and decrease their detrimental side effects on patients’ health. Nanomedicine is likely the pathway towards solving this challenge by enhancing both the therapeutic and diagnostic capabilities. In particular, plasmonic nanoparticles show remarkable potential due to their dual therapeutic functionalities as photothermal therapy agents and as radiosensitizers in radiotherapy. Their dual functionality, high biocompatibility, easy functionalization, and targeting capabilities make them potential agents for inducing efficient cancer cell death with minimal side effects. This review aims to identify the main challenges in the diagnosis and treatment of colorectal cancer. The heterogeneous nature of this cancer is also discussed from a single-cell point of view. The most relevant works in photo- and radiotherapy using nanotechnology-based therapies for colorectal cancer are addressed, ranging from in vitro studies (2D and 3D cell cultures) to in vivo studies and clinical trials. Although the results using nanoparticles as a photo- and radiosensitizers in photo- and radiotherapy are promising, preliminary studies showed that the possibility of combining both therapies must be explored to improve the treatment efficiency