Glycoprotein D actively induces rapid internalization of two nectin-1 isoforms during herpes simplex virus entry.
AuthorsStiles KM, Krummenacher C,
JournalVirology
PubMed ID20089288
'Entry of herpes simplex virus (HSV) occurs either by fusion at the plasma membrane or by endocytosis and fusion with an endosome. Binding of glycoprotein D (gD) to a receptor such as nectin-1 is essential in both cases. We show that virion gD triggered the rapid down-regulation of nectin-1 with ... More
Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy.
AuthorsZaghi J, Goldenson B, Inayathullah M, Lossinsky AS, Masoumi A, Avagyan H, Mahanian M, Bernas M, Weinand M, Rosenthal MJ, Espinosa-Jeffrey A, de Vellis J, Teplow DB, Fiala M,
JournalActa Neuropathol
PubMed ID19139910
'Neuronal accumulation of oligomeric amyloid-beta (Alphabeta) is considered the proximal cause of neuronal demise in Alzheimer disease (AD) patients. Blood-borne macrophages might reduce Abeta stress to neurons by immigration into the brain and phagocytosis of Alphabeta. We tested migration and export across a blood-brain barrier model, and phagocytosis and clearance ... More
Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response.
AuthorsTang HL, Tang HM, Mak KH, Hu S, Wang SS, Wong KM, Wong CS, Wu HY, Law HT, Liu K, Talbot CC, Lau WK, Montell DJ, Fung MC,
JournalMol Biol Cell
PubMed ID22535522
'Apoptosis serves as a protective mechanism by eliminating damaged cells through programmed cell death. After apoptotic cells pass critical checkpoints, including mitochondrial fragmentation, executioner caspase activation, and DNA damage, it is assumed that cell death inevitably follows. However, this assumption has not been tested directly. Here we report an unexpected ... More
'ABSTRACT: BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells with the potential to differentiate into bone, cartilage, fat and muscle cells and are being investigated for their utility in cell-based transplantation therapy. Yet, adequate methods to track transplanted MSCs in vivo are limited, precluding functional studies. Quantum Dots (QDs) offer ... More
Engineering the brain tumor microenvironment enhances the efficacy of dendritic cell vaccination: implications for clinical trial design.
AuthorsMineharu Y, King GD, Muhammad AK, Bannykh S, Kroeger KM, Liu C, Lowenstein PR, Castro MG,
JournalClin Cancer Res
PubMed ID21632862
'Glioblastoma multiforme (GBM) is a deadly primary brain tumor. Clinical trials for GBM using dendritic cell (DC) vaccination resulted in antitumor immune responses. Herein, we tested the hypothesis that combining in situ (intratumoral) Ad-Flt3L/Ad-TK-mediated gene therapy with DC vaccination would increase therapeutic efficacy and antitumor immunity. We first assessed the ... More
Tyrosine 23 phosphorylation-dependent cell-surface localization of annexin A2 is required for invasion and metastases of pancreatic cancer.
AuthorsZheng L, Foley K, Huang L, Leubner A, Mo G, Olino K, Edil BH, Mizuma M, Sharma R, Le DT, Anders RA, Illei PB, Van Eyk JE, Maitra A, Laheru D, Jaffee EM,
JournalPLoS One
PubMed ID21572519
'The aggressiveness of pancreatic ductal adenocarcinoma (PDA) is characterized by its high metastatic potential and lack of effective therapies, which is the result of a lack of understanding of the mechanisms involved in promoting PDA metastases. We identified Annexin A2 (ANXA2), a member of the Annexin family of calcium-dependent phospholipid ... More
Quantum dots for human mesenchymal stem cells labeling. A size-dependent autophagy activation.
AuthorsSeleverstov O, Zabirnyk O, Zscharnack M, Bulavina L, Nowicki M, Heinrich JM, Yezhelyev M, Emmrich F, O'Regan R, Bader A,
JournalNano Lett
PubMed ID17163713
Lately certain cytotoxicity of quantum dots (QDs) and some deleterious effects of labeling procedure on stem cells differentiation abilities were shown. In the present study we compared cytotoxicity and intracellular processing of two different-sized protein-conjugated QDs after labeling of the human mesenchymal stem cells (hMSC). An asymmetrical intracellular uptake of ... More
Semiconductor nanocrystals in autophagy research: methodology improvement at nanosized scale.
AuthorsSeleverstov O, Phang JM, Zabirnyk O,
JournalMethods Enzymol
PubMed ID19200889
Our recent findings establish a functional link between foreign nanosized bodies and autophagy. We find that nanoparticles (NP) within a certain size range act as potent autophagy activators, and that autophagic flux is an underlying physiological process of the cellular clearance of the NP. Therefore, NP may be used to ... More
In vivo study of the effects of peptide-conjugated near-infrared fluorescent quantum dots on the tumorigenic and lymphatic metastatic capacities of squamous cell carcinoma cell line Tca8113 and U14.
AuthorsLi ZG, Yang K, Cao YA, Zheng G, Sun DP, Zhao C, Yang J,
JournalInt J Mol Sci
PubMed ID20480027
Quantum dots (QDs) have great potential in non-invasive monitoring and imaging of tumor cells in vivo, but it is unknown if QDs affect their tumorigenesis and metastasis. Here, we applied peptide-conjugated near-infrared fluorescent QDs (NIRF-QDs) to label the squamous cell carcinoma cells Tca8113 and U14. We tested the proliferation and ... More
Diabetes impairs the interactions between long-term hematopoietic stem cells and osteopontin-positive cells in the endosteal niche of mouse bone marrow.
AuthorsChiba H, Ataka K, Iba K, Nagaishi K, Yamashita T, Fujimiya M,
Journal
PubMed ID23885062
Hematopoietic stem cells (HSCs) are maintained, and their division/proliferation and quiescence are regulated in the microenvironments, niches, in the bone marrow. Although diabetes is known to induce abnormalities in HSC mobilization and proliferation through chemokine and chemokine receptors, little is known about the interaction between long-term HSCs (LT-HSCs) and osteopontin-positive ... More
Segmental versican expression in the trabecular meshwork and involvement in outflow facility.
Versican is a large proteoglycan with numerous chondroitin sulfate (CS) glycosaminoglycan (GAG) side chains attached. To assess versican's potential contributions to aqueous humor outflow resistance, its segmental distribution in the trabecular meshwork (TM) and the effect on outflow facility of silencing the versican gene were evaluated. Fluorescent quantum dots (Qdots) ... More
MEF2C enhances dopaminergic neuron differentiation of human embryonic stem cells in a parkinsonian rat model.
AuthorsCho EG, Zaremba JD, McKercher SR, Talantova M, Tu S, Masliah E, Chan SF, Nakanishi N, Terskikh A, Lipton SA,
JournalPLoS One
PubMed ID21901155
Human embryonic stem cells (hESCs) can potentially differentiate into any cell type, including dopaminergic neurons to treat Parkinson's disease (PD), but hyperproliferation and tumor formation must be avoided. Accordingly, we use myocyte enhancer factor 2C (MEF2C) as a neurogenic and anti-apoptotic transcription factor to generate neurons from hESC-derived neural stem/progenitor ... More
Identification and characterization of a novel multipotent sub-population of Sca-1? cardiac progenitor cells for myocardial regeneration.
AuthorsTakamiya M, Haider KH, Ashraf M,
JournalPLoS One
PubMed ID21980409
METHODS AND RESULTS: The cardiac stem/progenitor cells from adult mice were seeded at low density in serum-free medium. The colonies thus obtained were expanded separately and assessed for expression of stem cell antigen-1 (Sca-1). Two colonies each with high Sca-1 (CSH1; 95.9%; CSH2; 90.6%) and low Sca-1 (CSL1; 37.1%; CSL2; ... More
Generation and labeling of murine bone marrow-derived dendritic cells with Qdot nanocrystals for tracking studies.
AuthorsMuccioli M, Pate M, Omosebi O, Benencia F,
JournalJ Vis Exp
PubMed ID21673641
Dendritic cells (DCs) are professional antigen presenting cells (APCs) found in peripheral tissues and in immunological organs such as thymus, bone marrow, spleen, lymph nodes and Peyer's patches. DCs present in peripheral tissues sample the organism for the presence of antigens, which they take up, process and present in their ... More
Arousal of cancer-associated stroma: overexpression of palladin activates fibroblasts to promote tumor invasion.
AuthorsBrentnall TA, Lai LA, Coleman J, Bronner MP, Pan S, Chen R,
JournalPLoS One
PubMed ID22291919
Cancer-associated fibroblasts, comprised of activated fibroblasts or myofibroblasts, are found in the stroma surrounding solid tumors. These myofibroblasts promote invasion and metastasis of cancer cells. Mechanisms regulating the activation of the fibroblasts and the initiation of invasive tumorigenesis are of great interest. Upregulation of the cytoskeletal protein, palladin, has been ... More
Conversion of vascular endothelial cells into multipotent stem-like cells.
Mesenchymal stem cells can give rise to several cell types, but varying results depending on isolation methods and tissue source have led to controversies about their usefulness in clinical medicine. Here we show that vascular endothelial cells can transform into multipotent stem-like cells by an activin-like kinase-2 (ALK2) receptor-dependent mechanism. ... More
Herpes simplex virus glycoprotein D interferes with binding of herpesvirus entry mediator to its ligands through downregulation and direct competition.
To initiate membrane fusion and virus entry, herpes simplex virus (HSV) gD binds to a cellular receptor such as herpesvirus entry mediator (HVEM). HVEM is a tumor necrosis factor (TNF) receptor family member with four natural ligands that either stimulate (LIGHT and LTa) or inhibit (BTLA and CD160) T cell ... More
Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect.
Intravenous (IV) stem cell delivery for regenerative tissue therapy has been increasingly used in both experimental and clinical trials. However, recent data suggest that the majority of administered stem cells are initially trapped in the lungs. We sought to investigate variables that may affect this pulmonary first-pass effect. In anesthetized ... More
Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein.
AuthorsDesplats P, Lee HJ, Bae EJ, Patrick C, Rockenstein E, Crews L, Spencer B, Masliah E, Lee SJ,
JournalProc Natl Acad Sci U S A
PubMed ID19651612
Neuronal accumulation of alpha-synuclein and Lewy body formation are characteristic to many neurodegenerative diseases, including Parkinson's disease (PD). This Lewy pathology appears to spread throughout the brain as the disease progresses. Furthermore, recent studies showed the occurrence of Lewy pathology in neurons grafted into the brains of PD patients, suggesting ... More
Intravenous mesenchymal stem cell therapy for traumatic brain injury.
Cell therapy has shown preclinical promise in the treatment of many diseases, and its application is being translated to the clinical arena. Intravenous mesenchymal stem cell (MSC) therapy has been shown to improve functional recovery after traumatic brain injury (TBI). Herein, the authors report on their attempts to reproduce such ... More
Compartment-specific transcription factors orchestrate angiogenesis gradients in the embryonic brain.
AuthorsVasudevan A, Long JE, Crandall JE, Rubenstein JL, Bhide PG,
JournalNat Neurosci
PubMed ID18344991
Prevailing notions of cerebral vascularization imply that blood vessels sprout passively into the brain parenchyma from pial vascular plexuses to meet metabolic needs of growing neuronal populations. Endothelial cells, building blocks of blood vessels, are thought to be homogeneous in the brain with respect to their origins, gene expression patterns ... More
Quantum dot imaging for embryonic stem cells.
AuthorsLin S, Xie X, Patel MR, Yang YH, Li Z, Cao F, Gheysens O, Zhang Y, Gambhir SS, Rao JH, Wu JC
JournalBMC Biotechnol
PubMed ID17925032
ABSTRACT: BACKGROUND: Semiconductor quantum dots (QDs) hold growing potential for cellular imaging both in vitro and in vivo. In this report, we aimed to evaluate the in vivo multiplex and long-term imaging of mouse embryonic stem (ES) cells labeled with Qtracker delivered quantum dots (QDs). RESULTS: Murine ES cells were ... More
Pulmonary artery adventitial fibroblasts cooperate with vasa vasorum endothelial cells to regulate vasa vasorum neovascularization: a process mediated by hypoxia and endothelin-1.
AuthorsDavie NJ, Gerasimovskaya EV, Hofmeister SE, Richman AP, Jones PL, Reeves JT, Stenmark KR
JournalAm J Pathol
PubMed ID16723696
The precise cellular and molecular mechanisms regulating adventitial vasa vasorum neovascularization, which occurs in the pulmonary arterial circulation in response to hypoxia, remain unknown. Here, using a technique to isolate and culture adventitial fibroblasts (AdvFBs) and vasa vasorum endothelial cells (VVECs) from the adventitia of pulmonary arteries, we report that ... More
Niche-dependent translineage commitment of endothelial progenitor cells, not cell fusion in general, into myocardial lineage cells.
AuthorsMurasawa S, Kawamoto A, Horii M, Nakamori S, Asahara T
JournalArterioscler Thromb Vasc Biol
PubMed ID15860746
OBJECTIVE: Previous studies from our laboratory have shown therapeutic potential of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial ischemia. Our purpose was to investigate the mechanisms regulating EPC contribution to myocardial regeneration. METHODS AND RESULTS: To evaluate niche-dependent expression profiles of EPCs in vitro, we performed coculture using ... More
Genetically Engineered Multilineage-Differentiating Stress-Enduring Cells as Cellular Vehicles against Malignant Gliomas.
AuthorsYamasaki T, Wakao S, Kawaji H, Koizumi S, Sameshima T, Dezawa M, Namba H
JournalMol Ther Oncolytics
PubMed ID28748212
'Malignant glioma, the most common malignant brain tumor in adults, is difficult to treat due to its aggressive invasive nature. Enzyme/prodrug suicide gene therapy based on the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) system is an efficient strategy for treating malignant gliomas. In the present study, we evaluated treatment ... More
Pre-aggregation of scalp progenitor dermal and epidermal stem cells activates the WNT pathway and promotes hair follicle formation in in vitro and in vivo systems.
Authors
JournalStem Cell Res Ther
PubMed ID31856904
Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis.
Authors
JournalCell
PubMed ID33417861
Nanoparticle vesicle encoding for imaging and tracking cell populations.
Authors
JournalNat Methods
PubMed ID25218182
Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia.
AuthorsBan Y, Mai J, Li X, Mitchell-Flack M, Zhang T, Zhang L, Chouchane L, Ferrari M, Shen H, Ma X
JournalCancer Res
PubMed ID28416485
The tumor-promoting potential of CCL5 has been proposed but remains poorly understood. We demonstrate here that an autocrine CCL5-CCR5 axis is a major regulator of immunosuppressive myeloid cells (IMC) of both monocytic and granulocytic lineages. The absence of the autocrine CCL5 abrogated the generation of granulocytic myeloid-derived suppressor cells and ... More
Adhesion forces and cortical tension couple cell proliferation and differentiation to drive epidermal stratification.
AuthorsMiroshnikova YA, Le HQ, Schneider D, Thalheim T, Rübsam M, Bremicker N, Polleux J, Kamprad N, Tarantola M, Wang I, Balland M, Niessen CM, Galle J, Wickström SA
JournalNat Cell Biol
PubMed ID29230016
To establish and maintain organ structure and function, tissues need to balance stem cell proliferation and differentiation rates and coordinate cell fate with position. By quantifying and modelling tissue stress and deformation in the mammalian epidermis, we find that this balance is coordinated through local mechanical forces generated by cell ... More
Novel Small Molecules Targeting the Intrinsically Disordered Structural Ensemble of a-Synuclein Protect Against Diverse a-Synuclein Mediated Dysfunctions.
AuthorsTóth G, Neumann T, Berthet A, Masliah E, Spencer B, Tao J, Jobling MF, Gardai SJ, Bertoncini CW, Cremades N, Bova M, Ballaron S, Chen XH, Mao W, Nguyen P, Tabios MC, Tambe MA, Rochet JC, Junker HD, Schwizer D, Sekul R, Ott I, Anderson JP, Szoke B, Hoffman W, Christodoulou J, Yednock T, Agard DA, Schenk D, McConlogue L
JournalSci Rep
PubMed ID31740740
The over-expression and aggregation of a-synuclein (aSyn) are linked to the onset and pathology of Parkinson's disease. Native monomeric aSyn exists in an intrinsically disordered ensemble of interconverting conformations, which has made its therapeutic targeting by small molecules highly challenging. Nonetheless, here we successfully target the monomeric structural ensemble of ... More
Fluorescence-based tracing of transplanted intestinal epithelial cells using confocal laser endomicroscopy.
Intestinal stem cell transplantation has been shown to promote mucosal healing and to engender fully functional epithelium in experimental colitis. Hence, stem cell therapies may provide an innovative approach to accomplish mucosal healing in patients with debilitating conditions such as inflammatory bowel disease. However, an approach to label and trace ... More
A surgical orthotopic approach for studying the invasive progression of human bladder cancer.
AuthorsLorenzatti Hiles G, Cates AL, El-Sawy L, Day KC, Broses LJ, Han AL, Briggs HL, Emamdjomeh A, Chou A, Abel EV, Liebert M, Palmbos PL, Udager AM, Keller ET, Day ML
JournalNat Protoc
PubMed ID30683938
The invasion of bladder cancer into the sub-urothelial muscle and vasculature are key determinants leading to lethal metastatic progression. However, the molecular basis is poorly understood, partly because of the lack of uncomplicated and reliable models that recapitulate the biology of locally invasive disease. We developed a surgical grafting technique, ... More