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Xue Liu, Yingying Liu, Zaofeng Yang, Wen Ning
Follistatin like-1 (Fstl1) is a secreted glycoprotein and can be up-regulated by TGF-β1. To better study the function of Fstl1 in lung development, we examined Fstl1 expression in the developing lung, in a cell type specific manner, using a tamoxifen inducible Fstl1-reporter mouse strain. Our results show that Fstl1 is ubiquitously expressed at saccular stage in the developing lung. At E18.5, Fstl1 expression is robust in most type of mesenchymal cells, including airway smooth muscle cells surrounding airways, vascular smooth muscle cells, endothelial cells, and vascular pericytes from blood vessel, but not PDGFRα+ fibroblasts in the distal alveolar sacs...
June 18, 2018: Journal of Molecular Histology
Benjamin D Gastfriend, Sean P Palecek, Eric V Shusta
The blood-brain barrier (BBB) regulates the transport of ions, nutrients, and metabolites to help maintain proper brain function. This restrictive interface formed by brain microvascular endothelial cells excludes the majority of small and large molecule drugs from entering the brain, and blood-brain barrier dysfunction is a signature of many neurological diseases. Thus, in vitro models of the BBB based on brain endothelial cells have been developed to facilitate screening drugs for BBB permeability. However, while brain endothelial cells form the main interface, they work in concert with other brain-resident cells such as neural progenitor cells, pericytes, astrocytes, and neurons to form the neurovascular unit (NVU)...
March 2018: Current Opinion in Biomedical Engineering
Marisa Karow, J Gray Camp, Sven Falk, Tobias Gerber, Abhijeet Pataskar, Malgorzata Gac-Santel, Jorge Kageyama, Agnieska Brazovskaja, Angela Garding, Wenqiang Fan, Therese Riedemann, Antonella Casamassa, Andrej Smiyakin, Christian Schichor, Magdalena Götz, Vijay K Tiwari, Barbara Treutlein, Benedikt Berninger
Ectopic expression of defined transcription factors can force direct cell-fate conversion from one lineage to another in the absence of cell division. Several transcription factor cocktails have enabled successful reprogramming of various somatic cell types into induced neurons (iNs) of distinct neurotransmitter phenotype. However, the nature of the intermediate states that drive the reprogramming trajectory toward distinct iN types is largely unknown. Here we show that successful direct reprogramming of adult human brain pericytes into functional iNs by Ascl1 and Sox2 encompasses transient activation of a neural stem cell-like gene expression program that precedes bifurcation into distinct neuronal lineages...
June 18, 2018: Nature Neuroscience
Michael Munroe, Ziad S Mahmassani, Svyatoslav Dvoretskiy, Justin J Reid, Benjamin F Miller, Karyn Hamilton, Justin S Rhodes, Marni D Boppart
β-hydroxy β-methylbutyrate (HMB) is a nutritional supplement purported to enhance skeletal muscle mass and strength, as well as cognitive function in older adults. The purpose of this study was to determine the potential for long-term HMB supplementation to preserve muscle function and cognition in aged mice, as well as provide evidence of a link between vessel-associated pericyte function and outcomes. Four- (Adult/Ad) and 17 month-old (Aged/Ag) C57BL/6J mice consumed chow containing 600 mg/kg BW/day of either Ca-HMB (Ad, n=16; Ag, n=17) or Ca-Lactate (Ad, n=16; Ag, n=17) for 6 months...
June 19, 2018: Nutritional Neuroscience
Leon Felipe Ruiz-Arriaga, Ana Laura Ramirez Teran, Carlos Ortiz-Hidalgo, Veronica Fonte-Avalos, Sonia Toussaint-Caire, Ma Elisa Vega-Memije, Mariana CatalinaDe Anda-Juarez
Myopericytoma is a soft-tissue tumor of perivascular cells (pericytes). It is slow-growing, usually asymptomatic, and generally benign, although a malignant variant has been described. The etiology is unknown, but it has been associated with local trauma. The most common location is on the distal extremities. Histologically, it is characterized by a well-circumscribed, non-encapsulated proliferation of spindle shaped cells similar to myofibroblasts with oval nuclei and eosinophilic cytoplasm, arranged in perivascular concentric rings...
April 15, 2018: Dermatology Online Journal
J Vérité, T Janet, D Chassaing, B Fauconneau, H Rabeony, G Page
BACKGROUND: Alzheimer's disease is widely described since the discovery of histopathological lesions in Mrs. Auguste Deter in 1906. However to date, there is no effective treatment to deal with the many cellular and molecular alterations. The complexity is even higher with the growing evidence of involvement of the peripheral blood mononuclear cells (PBMCs). Indeed, monocytes and T cells are shown in the cerebral parenchyma of AD patients, and these cells grafted to the periphery are able to go through the blood-brain barrier (BBB) in transgenic mouse models...
June 13, 2018: Journal of Neuroinflammation
Laurène M André, C Rosanne M Ausems, Derick G Wansink, Bé Wieringa
Myotonic dystrophy type 1 (DM1) and 2 (DM2) are autosomal dominant degenerative neuromuscular disorders characterized by progressive skeletal muscle weakness, atrophy, and myotonia with progeroid features. Although both DM1 and DM2 are characterized by skeletal muscle dysfunction and also share other clinical features, the diseases differ in the muscle groups that are affected. In DM1, distal muscles are mainly affected, whereas in DM2 problems are mostly found in proximal muscles. In addition, manifestation in DM1 is generally more severe, with possible congenital or childhood-onset of disease and prominent CNS involvement...
2018: Frontiers in Neurology
Leon C D Smyth, Justin Rustenhoven, Emma L Scotter, Patrick Schweder, Richard L M Faull, Thomas I H Park, Mike Dragunow
Brain pericytes and vascular smooth muscle cells (vSMCs) are a critical component of the neurovascular unit and are important in regulating cerebral blood flow and blood-brain barrier integrity. Identification of subtypes of mural cells in tissue and in vitro is important to any study of their function, therefore we identified distinct mural cell morphologies in neurologically normal post-mortem human brain. Further, the distribution of mural cell markers platelet-derived growth factor receptor-β (PDGFRβ), α-smooth muscle actin (αSMA), CD13, neural/glial antigen-2 (NG2), CD146 and desmin was examined...
June 7, 2018: Journal of Chemical Neuroanatomy
Patricia Miranda-Azpiazu, Stavros Panagiotou, Gin Jose, Sikha Saha
Blood brain barrier (BBB) cells play key roles in the physiology and pathology of the central nervous system (CNS). BBB dysfunction is implicated in many neurodegenerative diseases, including Alzheimer's disease (AD). The BBB consists of capillary endothelial cells, pericytes encircling the endothelium and surrounding astrocytes extending their processes towards it. Although there have been many attempts to develop in vitro BBB models, the complex interaction between these cell types makes it extremely difficult to determine their individual contribution to neurotoxicity in vivo...
June 8, 2018: Scientific Reports
Trivia Frazier, Stephen Lee, Annie Bowles, Julie Semon, Bruce Bunnell, Xiying Wu, Jeffrey Gimble
Adipose tissue is now recognized as a functional organ that contains cellular heterogeneity and diversity within anatomical depots. The stromal vascular fraction (SVF) of adipose contains endothelial progenitors, fibroblasts, lymphocytes, monocyte/macrophages, pericytes, pre-adipocytes, and stromal/stem cells, among others. In recent years, there has been a growing appreciation of the influence of age and gender in the field of stem cell biology. Yet few studies have evaluated the influence of biological age or sex on either SVF cell heterogeneity or immunophenotype...
June 8, 2018: Adipocyte
Robert A Kloner, Kevin S King, Michael Harrington
The no-reflow phenomenon refers to the observation that when an organ is made ischemic by occlusion of a large artery supplying it, restoration of patency in that artery does not restore perfusion to the microvasculature supplying the parenchyma of that organ. This has been observed following prolonged arterial occlusions in the heart (30 to 90 minutes), brain, skin, and kidney. In experimental models, zones of no-reflow in the heart are characterized by ultrastructural microvascular damage, including focal endothelial swelling obstructing the lumen of small vessels...
June 8, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Sevil Köse, Nilgün Yersal, Selin Önen, Petek Korkusuz
Recent advances require a dual evaluation of germ and somatic stem cell niches with a regenerative medicine perspective. For a better point of view of the niche concept, it is needed to compare the microenvironments of those niches in respect to several components. The cellular environment of spermatogonial stem cells' niche consists of Sertoli cells, Leydig cells, vascular endothelial cells, epididymal fat cells, peritubular myoid cells while hematopoietic stem cells have mesenchymal stem cells, osteoblasts, osteoclasts, megacaryocytes, macrophages, vascular endothelial cells, pericytes and adipocytes in their microenvironment...
June 8, 2018: Advances in Experimental Medicine and Biology
Lucas Treps
Glioblastoma multiforme (GBM) is a highly vascularized and aggressive brain tumor. Despite aggressive standard care, GBM remains predominantly fatal; hence new innovative therapies are required. Recent research published in The Journal of Pathology has identified the CGKRK peptide as a promising tool to specifically target tumor vasculature from high grade glioma. This tumor vessel homing peptide was fused to the TNF superfamily member LIGHT/TNFSF14 and injected intravenously to murine orthotopic GBM models...
June 7, 2018: Journal of Pathology
Giuseppe Castellano, Rossana Franzin, Alessandra Stasi, Chiara Divella, Fabio Sallustio, Paola Pontrelli, Giuseppe Lucarelli, Michele Battaglia, Francesco Staffieri, Antonio Crovace, Giovanni Stallone, Marc Seelen, Mohamed R Daha, Giuseppe Grandaliano, Loreto Gesualdo
Pericytes are one of the principal sources of scar-forming myofibroblasts in chronic kidneys disease. However, the modulation of pericyte-to-myofibroblast transdifferentiation (PMT) in the early phases of acute kidney injury is poorly understood. Here, we investigated the role of complement in inducing PMT after transplantation. Using a swine model of renal ischemia/reperfusion (I/R) injury, we found the occurrence of PMT after 24 h of I/R injury as demonstrated by reduction of PDGFRβ+ /NG2+ cells with increase in myofibroblasts marker αSMA...
2018: Frontiers in Immunology
B J Klotz, K S Lim, Y X Chang, B J Soliman, I Pennings, F P Melchels, F P Melchels, A J Rosenberg, J Malda, D Gawlittal
In engineering of tissue analogues, upscaling to clinically-relevant sized constructs remains a significant challenge. The successful integration of a vascular network throughout the engineered tissue is anticipated to overcome the lack of nutrient and oxygen supply to residing cells. This work aimed at developing a multiscale bone-tissue-specific vascularisation strategy. Engineering pre-vascularised bone leads to biological and fabrication dilemmas. To fabricate channels endowed with an endothelium and suitable for osteogenesis, rather stiff materials are preferable, while capillarisation requires soft matrices...
May 30, 2018: European Cells & Materials
Hikaru Hashitani, Retsu Mitsui, Kyoko Miwa-Nishimura, Michelle Lam
Mural cells in microvasculature of visceral organs develop spontaneous Ca2+ transients. However, the mechanisms underlying the integration of these Ca2+ transients within a microvascular unit remain to be elucidated. Here, the origin of spontaneous Ca2+ transients and their propagation in the bladder suburothelial microvasculature were explored. Cal-520 fluorescence Ca2+ imaging and immunohistochemistry were carried out on mural cells using mice expressing DsRed under control of the NG2 promotor. NG2(+) pericytes in both pre-capillary arterioles (PCAs) and capillaries developed synchronous spontaneous Ca2+ transients...
June 6, 2018: Journal of Physiology
Szilvia Veszelka, András Tóth, Fruzsina R Walter, Andrea E Tóth, Ilona Gróf, Mária Mészáros, Alexandra Bocsik, Éva Hellinger, Monika Vastag, Gábor Rákhely, Mária A Deli
Cell culture-based blood-brain barrier (BBB) models are useful tools for screening of CNS drug candidates. Cell sources for BBB models include primary brain endothelial cells or immortalized brain endothelial cell lines. Despite their well-known differences, epithelial cell lines are also used as surrogate models for testing neuropharmaceuticals. The aim of the present study was to compare the expression of selected BBB related genes including tight junction proteins, solute carriers (SLC), ABC transporters, metabolic enzymes and to describe the paracellular properties of nine different culture models...
2018: Frontiers in Molecular Neuroscience
Zhiqiang Hou, Xiaohan Wang, Jing Cai, Jinhui Zhang, Ahmed Hassan, Manfred Auer, Xiaorui Shi
Normal blood supply to the cochlea is critical for hearing. Noise damages auditory sensory cells and has a marked effect on the microvasculature in the cochlear lateral wall. Pericytes in the stria vascularis (strial pericytes) are particularly vulnerable and sensitive to acoustic trauma. Exposure of NG2DsRedBAC transgenic mice (6-8 weeks old) to wide-band noise at a level of 120 dB for 3 h per day for 2 consecutive days produced a significant hearing threshold shift and caused pericytes to protrude and migrate from their normal endothelial attachment sites...
June 4, 2018: Journal of the Association for Research in Otolaryngology: JARO
Changsi Cai, Jonas C Fordsmann, Sofie H Jensen, Bodil Gesslein, Micael Lønstrup, Bjørn O Hald, Stefan A Zambach, Birger Brodin, Martin J Lauritzen
Functional neuroimaging, such as fMRI, is based on coupling neuronal activity and accompanying changes in cerebral blood flow (CBF) and metabolism. However, the relationship between CBF and events at the level of the penetrating arterioles and capillaries is not well established. Recent findings suggest an active role of capillaries in CBF control, and pericytes on capillaries may be major regulators of CBF and initiators of functional imaging signals. Here, using two-photon microscopy of brains in living mice, we demonstrate that stimulation-evoked increases in synaptic activity in the mouse somatosensory cortex evokes capillary dilation starting mostly at the first- or second-order capillary, propagating upstream and downstream at 5-20 µm/s...
June 4, 2018: Proceedings of the National Academy of Sciences of the United States of America
Nina Schultz, Elin Byman, Malin Wennström
Islet amyloid polypeptide (IAPP) forms toxic aggregates in the brain of patients with Alzheimer's disease (AD). Whether IAPP also affects the retina in these patients is still unknown. Levels of IAPP in soluble and insoluble homogenate fractions of retina and hippocampus from AD patients and nondemented controls were analyzed using ELISA. Number of pericytes and vessel length were determined by analysis of immunostained retina and hippocampus. Insoluble retinal fractions of AD patients contained lower levels of unmodified IAPP, whereas soluble retinal fractions contained increased levels of the same...
June 1, 2018: Neurobiology of Aging
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