Yi Huang, Jie Gao, Yiduo Zhou, Shuo Wu, Yunpeng Shao, Haoliang Xue, Baixin Shen, Liucheng Ding, Zhongqing Wei
BACKGROUND: Diabetic cystopathy (DCP) is a chronic complication of diabetes mainly within the submucosal and muscular layers of the bladder due to the hyperglycemia-induced ischemia. As no effective therapies are currently available, the administration of optimized mesenchymal stem cells (MSCs) provides a potential treatment of DCP. Thus far, new strategy, such as genetic modification of MSCs, has been developed and has shown promising outcomes of various disorders. METHODS: This study was conducted using integrin-linked kinase (ILK) gene-modified bone marrow-derived stem cells (BMSCs) for streptozotocin (STZ)-induced diabetic cystopathy in a rat model...
July 10, 2020: Stem Cell Research & Therapy
Hanjin Cui, Ali Yang, Huajun Zhou, Yang Wang, Jiekun Luo, Jun Zhou, Tao Liu, Pengfei Li, Jing Zhou, En Hu, Zehui He, Wang Hu, Tao Tang
OBJECTIVE: Thrombin is a unique factor that triggers post-intracerebral hemorrhage (ICH) angiogenesis by increasing hypoxia-inducible factor-1α (HIF-1α) at the protein level. However, HIF-1α mRNA remains unchanged. MicroRNAs (miRNAs) mediate posttranscriptional regulation by suppressing protein translation from mRNAs. This study aimed to determine if miRNAs might be involved in thrombin-induced angiogenesis after ICH by targeting HIF-1α or its upstream prolyl hydroxylase domains (PHDs)...
May 15, 2020: Journal of Neurosurgery
Outi Huttala, Synnöve Staff, Tuula Heinonen, Johanna Mäenpää, Minna Tanner, Timo Ylikomi
Drug treatments have been designed to inhibit tumor angiogenesis in hope of stopping tumor growth. However, not all tumor types respond to this type of treatment. A screening method which identifies angiogenesis inducing cancer types would help predict the efficacy of angiogenesis-inhibiting drugs for the patients. Our goal is to develop (1) a cell assay to assess the angiogenic induction potential of patient-derived tumor cells, and (2) a protocol for culturing cancer cells on a vascular platform. We optimized the media composition and seeding density of cells (hASC, HUVEC, and cancer cells) to 48-, 96-, and even 384-well plate sizes to allow vascular formation and cancer cell proliferation and subsequent analysis with high throughput...
March 6, 2020: International Journal of Molecular Sciences
Veronica H Flood, Jessica Garcia, Sandra L Haberichter
PURPOSE OF REVIEW: Von Willebrand disease (VWD) is a common bleeding disorder, but diagnosis of VWD is challenging, particularly with type 1 VWD. Although most clinicians use specific tests of von Willebrand factor (VWF) activity to classify patients with VWD, genetic testing for VWF defects is another potential method of diagnosis. RECENT FINDINGS: Studies of patients with type 1 VWD report consistently that many, but not all, study participants have VWF gene defects...
June 28, 2019: Current Opinion in Hematology
Eric Manderstedt, Rosanna Nilsson, Christina Lind-Halldén, Rolf Ljung, Jan Astermark, Christer Halldén
Mutations are not identified in ~5% of hemophilia A and 10-35% of type 1 VWD patients. The bleeding tendency also varies among patients carrying the same causative mutation, potentially indicating variants in additional genes modifying the phenotype that cannot be identified by routine single-gene analysis. The F8, F9 and VWF genes were analyzed in parallel using an AmpliSeq strategy and Ion Torrent sequencing. Targeting all exonic positions showed an average read depth of >2000X and coverage close to 100% in 24 male patients with known disease-causing mutations...
2019: PloS One
Qian Zhang, Meiling Zhou, Xiangfeng Wu, Zhu Li, Bing Liu, Wenbin Gao, Jin Yue, Tao Liu
BACKGROUND: A stroke caused by angiostenosis always has a poor prognosis. Bone marrow stromal cells (BMSC) are widely applied in vascular regeneration. Recently, thrombospondin-4 (TSP4) was reported to promote the regeneration of blood vessels and enhance the function of endothelial cells in angiogenesis. In this work, we observed the therapeutic effect of TSP4-overexpressing BMSCs on angiogenesis post-stroke. METHODS: We subcloned the tsp4 gene into a lentivirus expression vector system and harvested the tsp4 lentivirus using 293FT cells...
April 4, 2019: Journal of Translational Medicine
Min-Hua Tseng, Jeng-Daw Tsai, I-Jung Tsai, Shih-Ming Huang, Jing-Long Huang, Wen-Lang Fan, Hwei-Jen Lee, Tai-Wei Wu, Shih-Hua Lin
Although atypical hemolytic uremic syndrome (aHUS) is a genetic disorder, molecular defects are detected in only 60% of patients. We aim to dissect the genetic background by whole exome sequence and the clinical characteristics of pediatric patients with aHUS. Ten patients (6 male and 4 female) with mean age 5.2 ± 5.0 years were enrolled. The age at onset ranged from 2 days to 11 years. Eighteen different mutations (17 missense, 2 nonsense, and 11 novel) on 7 complement and 3 coagulation genes were detected in all patients...
March 21, 2019: Clinica Chimica Acta; International Journal of Clinical Chemistry
Maryam Nakhaei-Nejad, Maikel Farhan, Anahita Mojiri, Hosna Jabbari, Allan G Murray, Nadia Jahroudi
Endothelial cells play a central role in physiological function and pathophysiology of blood vessels in health and disease. However, the molecular mechanism that establishes the endothelial phenotype, and contributes to its signature cell type-specific gene expression, is not yet understood. We studied the regulation of a highly endothelial-specific gene, von Willebrand factor (VWF), in induced pluripotent stem cells generated from primary endothelial cells (human umbilical vein endothelial cells [HUVEC] into a pluripotent state [HiPS]) and subsequently differentiated back into endothelial cells...
January 25, 2019: Stem Cells
L L Swystun, D Lillicrap
Plasma levels of the multimeric glycoprotein von Willebrand factor (VWF) constitute a complex quantitative trait with a continuous distribution and wide range in the normal population (50-200%). Quantitative deficiencies of VWF (< 50%) are associated with an increased risk of bleeding, whereas high plasma levels of VWF (> 150%) influence the risk of arterial and venous thromboembolism. Although environmental factors can strongly influence plasma VWF levels, it is estimated that approximately 65% of this variability is heritable...
September 23, 2018: Journal of Thrombosis and Haemostasis: JTH
Meisam Naeimi Kararoudi, Seyyed S Hejazi, Ezgi Elmas, Mats Hellström, Maryam Naeimi Kararoudi, Arvind M Padma, Dean Lee, Hamid Dolatshad
Genetically modified pigs have been considered favorable resources in xenotransplantation. Microinjection of randomly integrating transgenes into zygotes, somatic cell nuclear transfer, homologous recombination, zinc finger nucleases, transcription activator-like effector nucleases, and most recently, clustered regularly interspaced short palindromic repeats-cas9 (CRISPR/Cas9) are the techniques that have been used to generate these animals. Here, we provide an overview of the CRISPR approaches that have been used to modify genes which are vital in improving xenograft survival rate, including cytidine monophosphate- N -acetylneuraminic acid hydroxylase, B1,4N-acetylgalactosaminyltransferase, isoglobotrihexosylceramide synthase, class I MHC, von Willebrand factor, C3, and porcine endogenous retroviruses...
2018: Frontiers in Immunology
Richard T Waldron, Aurelia Lugea, Aiste Gulla, Stephen J Pandol
Acute pancreatitis (AP) is a painful and potentially life-threatening disorder with the potential for therapeutic interventions. Biomarkers that characterize cases by severity and pathogenic mechanisms involved are not yet available but needed for the implementation of rational therapies. Here, we used shotgun proteomics to obtain information from plasma samples about local and systemic pathologies taking place during cases of alcoholic AP. Plasma was obtained at Kaunas University of Medicine Hospital (Lithuania) from 12 AP patients of alcohol related etiology (median age of 40) within 24 h of presentation, and 12 age-matched, healthy controls...
2018: Frontiers in Physiology
Isabella Garagiola, Roberta Palla, Flora Peyvandi
Although significant advances in hemophilia treatment have improved patient outcomes and quality of life, one of the greatest complications in severe hemophilia A is the development of anti-Factor VIII (FVIII) antibodies that inhibit FVIII activity in almost 30% of previously untreated patients (PUPs). Inhibitors make very difficult the management of patients and increase their morbidity and mortality reducing drastically their quality of life. Numerous studies have investigated the mechanisms leading to the development of FVIII inhibitors...
August 2018: Thrombosis Research
Johana Hrdinová, Silvia D'Angelo, Nuno A G Graça, Bogac Ercig, Karen Vanhoorelbeke, Agnès Veyradier, Jan Voorberg, Paul Coppo
Although outstanding progress has been made in understanding the pathophysiology of thrombotic thrombocytopenic purpura (TTP), knowledge of the immunopathogenesis of the disease is only at an early stage. Anti-ADAMTS13 auto-antibodies were shown to block proteolysis of von Willebrand factor and/or induce ADAMTS13 clearance from the circulation. However, it still remains to identify which immune cells are involved in the production of anti-ADAMTS13 autoantibodies, and therefore account for the remarkable efficacy of the B-cell depleting agents in this disease...
July 2018: Haematologica
Rui Zhang, Mengting Qin, Jie Shi, Lu Tan, Jiamin Xu, Zhenyan Tian, Yuhui Wu, Yuxuan Li, Yitian Li, Ning Wang
In the present study, the Pif gene of the freshwater pearl aquaculture mussel, Hyriopsis cumingii (HcPif) was successfully cloned and functionally characterized. The full sequence of HcPif gene consists of 3415 base pairs, which putatively encode two proteins, HcPif90 and HcPif80. A sequence analysis revealed that HcPif contained a von Willebrand factor type A domain and a chitin-binding domain, and shared many functional residues with other Pif homologues. A highly conserved sequence, FKGLDEIELML, at the C-terminus of Pif80s was identified as the key functional site...
April 2018: 3 Biotech
Simon Limbrecht Mogensen, Martin Krøyer Rasmussen, Niels Oksbjerg, Jette Feveile Young, Jens Rolighed Larsen
OBJECTIVES: Heart failure is a significant cause of mortality worldwide, and most current therapies treat only its symptoms. The results of cardiac stem cell research suggest a promising treatment option for heart failure, but there is currently an unmet demand for better research models. We have therefore, for the first time, isolated, expanded and differentiated progenitor cells obtained from juvenile pig hearts to use as a platform for cardiac stem cell research. DESIGN: Progenitor cells were isolated from the left ventricles of porcine hearts using collagenase enzymatic digestion and Percoll® -gradient centrifugation...
February 2018: Scandinavian Cardiovascular Journal: SCJ
P Boisseau, C Debord, M Eveillard, A Quéméner, M Sigaud, M Giraud, P Talarmain, C Thomas, G Landeau, S Bezieau, B Pan Petesch, M C Béné, M Fouassier
Bernard-Soulier syndrome (BSS) is an autosomal recessive major thrombocytopathy, the symptoms of which are mainly marked by mucocutaneous bleeding. This rare disease, initially described in the 1970s, is the result of an abnormal formation of the glycoprotein complex Ib-IX-V (GP Ib-IX-V), a platelet receptor of von Willebrand factor. A large number of mutations, sometimes involving the GP9 gene, have been described as possibly responsible for the disease. We report here the case of a BSS patient who presented with persistent thrombocytopenia (31x109 /L) and decreased surface expression of GPIb-IX-V on large platelets with anisocytosis...
May 2018: Platelets
Jian Li, Holger Jahr, Wei Zheng, Pei-Gen Ren
The reconstruction of critically sized bone defects remains a serious clinical problem because of poor angiogenesis within tissue-engineered scaffolds during repair, which gives rise to a lack of sufficient blood supply and causes necrosis of the new tissues. Rapid vascularization is a vital prerequisite for new tissue survival and integration with existing host tissue. The de novo generation of vasculature in scaffolds is one of the most important steps in making bone regeneration more efficient, allowing repairing tissue to grow into a scaffold...
September 7, 2017: Journal of Visualized Experiments: JoVE
Hisashi Sahara, Hironosuke Watanabe, Thomas Pomposelli, Kazuhiko Yamada
PURPOSE OF REVIEW: This review describes the most recent progress in xeno lung transplantation (XLTx) to date. It describes the potential mechanisms of early xeno lung graft loss, as well as the latest therapeutic strategies to overcome them. RECENT FINDINGS: Using ex-vivo perfusion models of porcine lungs with human blood, the use of genetically modified pig lungs along with novel pharmaceutical approaches has recently been studied. Strategies that have demonstrated improved lung survival include the knockout of known xenoantigens (GalTKO and N-glycolylneuraminic acid-KO), genes that regulate complement activation (hCD46 and hCD55), as well as the inflammation/coagulation cascade (human leukocyte antigen-E, human thrombomodulin, human endothelial protein C receptor, hCD47, hCD39, hCD73 and heme oxygenase-1)...
December 2017: Current Opinion in Organ Transplantation
Xin-Peng Han, Fang-Qi Zhang, Xiang-Shu Tan, Liang Liu, Wen-Xian Ma, Hai-Feng Ou-Yang, Chang-Gui Wu
There was no effective measures can be obtained at present to reverse or prevent airway remodeling. We investigated the therapeutic effect of Erythropoietin (EPO) gene modified mesenchymal stem cells (MSCs) on asthmatic airway remodeling and the possible underlied molecular mechanisms. EPO gene was transfected into MSCs via lentivirus vector. The transfected cells (EPO-MSCs) were identified by flow cytometry and the EPO secreting function was detected by PCR and Western blot. MSCs or EPO-MSCs were administrated to albumin (OVA)-induced chronic asthmatic mouse model via tail veins...
January 2018: Journal of Cellular Biochemistry
Maria Isabel Castellanos, Jordi Guillem-Marti, Carlos Mas-Moruno, Maribel Díaz-Ricart, Ginés Escolar, Maria Pau Ginebra, Francisco Javier Gil, Marta Pegueroles, Jose María Manero
Immobilization of bioactive peptide sequences on CoCr surfaces is an effective route to improve endothelialization, which is of great interest for cardiovascular stents. In this work, we explored the effect of physical and covalent immoblization of RGDS, YIGSR and their equimolar combination peptides on endothelial cells (EC) and smooth muscle cell (SMC) adhesion and on thrombogenicity. We extensively investigated using RT-qPCR, the expression by ECs cultured on functionalised CoCr surfaces of different genes...
April 2017: Journal of Biomedical Materials Research. Part A
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