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[PMID]:28747142
[Au] Autor:Zhao Y; Stepto H; Schneider CK
[Ad] Endereço:1 Division of Advanced Therapies, National Institute for Biological Standards and Control (NIBSC) , Medicines and Health Products Regulatory Agency (MHRA), South Mimms, United Kingdom .
[Ti] Título:Development of the First World Health Organization Lentiviral Vector Standard: Toward the Production Control and Standardization of Lentivirus-Based Gene Therapy Products.
[So] Source:Hum Gene Ther Methods;28(4):205-214, 2017 08.
[Is] ISSN:1946-6544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gene therapy is a rapidly evolving field. So far, there have been >2,400 gene therapy products in clinical trials and four products on the market. A prerequisite for producing gene therapy products is ensuring their quality and safety. This requires appropriately controlled and standardized production and testing procedures that result in consistent safety and efficacy. Assuring the quality and safety of lentivirus-based gene therapy products in particular presents a great challenge because they are cell-based multigene products that include viral and therapeutic proteins as well as modified cells. In addition to the continuous refinement of a product, changes in production sites and manufacturing processes have become more and more common, posing challenges to developers regarding reproducibility and comparability of results. This paper discusses the concept of developing a first World Health Organization International Standard, suitable for the standardization of assays and enabling comparison of cross-trial and cross-manufacturing results for this important vector platform. The standard will be expected to optimize the development of gene therapy medicinal products, which is especially important, given the usually orphan nature of the diseases to be treated, naturally hampering reproducibility and comparability of results.
[Mh] Termos MeSH primário: Terapia Genética/normas
Vetores Genéticos/normas
Lentivirus/genética
Organização Mundial da Saúde
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Terapia Genética/métodos
Vetores Genéticos/genética
Células HEK293
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180310
[Lr] Data última revisão:
180310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1089/hgtb.2017.078


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[PMID]:29178837
[Au] Autor:Spinozzi G; Calabria A; Brasca S; Beretta S; Merelli I; Milanesi L; Montini E
[Ad] Endereço:San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy.
[Ti] Título:VISPA2: a scalable pipeline for high-throughput identification and annotation of vector integration sites.
[So] Source:BMC Bioinformatics;18(1):520, 2017 Nov 25.
[Is] ISSN:1471-2105
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Bioinformatics tools designed to identify lentiviral or retroviral vector insertion sites in the genome of host cells are used to address the safety and long-term efficacy of hematopoietic stem cell gene therapy applications and to study the clonal dynamics of hematopoietic reconstitution. The increasing number of gene therapy clinical trials combined with the increasing amount of Next Generation Sequencing data, aimed at identifying integration sites, require both highly accurate and efficient computational software able to correctly process "big data" in a reasonable computational time. RESULTS: Here we present VISPA2 (Vector Integration Site Parallel Analysis, version 2), the latest optimized computational pipeline for integration site identification and analysis with the following features: (1) the sequence analysis for the integration site processing is fully compliant with paired-end reads and includes a sequence quality filter before and after the alignment on the target genome; (2) an heuristic algorithm to reduce false positive integration sites at nucleotide level to reduce the impact of Polymerase Chain Reaction or trimming/alignment artifacts; (3) a classification and annotation module for integration sites; (4) a user friendly web interface as researcher front-end to perform integration site analyses without computational skills; (5) the time speedup of all steps through parallelization (Hadoop free). CONCLUSIONS: We tested VISPA2 performances using simulated and real datasets of lentiviral vector integration sites, previously obtained from patients enrolled in a hematopoietic stem cell gene therapy clinical trial and compared the results with other preexisting tools for integration site analysis. On the computational side, VISPA2 showed a > 6-fold speedup and improved precision and recall metrics (1 and 0.97 respectively) compared to previously developed computational pipelines. These performances indicate that VISPA2 is a fast, reliable and user-friendly tool for integration site analysis, which allows gene therapy integration data to be handled in a cost and time effective fashion. Moreover, the web access of VISPA2 ( http://openserver.itb.cnr.it/vispa/ ) ensures accessibility and ease of usage to researches of a complex analytical tool. We released the source code of VISPA2 in a public repository ( https://bitbucket.org/andreacalabria/vispa2 ).
[Mh] Termos MeSH primário: Interface Usuário-Computador
[Mh] Termos MeSH secundário: Algoritmos
Terapia Genética
Vetores Genéticos/genética
Vetores Genéticos/metabolismo
Transplante de Células-Tronco Hematopoéticas
Células-Tronco Hematopoéticas/citologia
Células-Tronco Hematopoéticas/metabolismo
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Lentivirus/genética
Lentivirus/fisiologia
Alinhamento de Sequência
Internalização do Vírus
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1186/s12859-017-1937-9


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[PMID]:28741230
[Au] Autor:Velayudhan L; Ffytche D; Ballard C; Aarsland D
[Ad] Endereço:Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neurosciences, Kings College London, Box PO 70, De Crespigny Park, London, SE5 8AF, UK.
[Ti] Título:New Therapeutic Strategies for Lewy Body Dementias.
[So] Source:Curr Neurol Neurosci Rep;17(9):68, 2017 Sep.
[Is] ISSN:1534-6293
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This article reviews current treatment strategies and recent advances for the Lewy body dementias (LBDs). Current available symptom treatment strategies are based on monoaminergic, cholinergic and glutaminergic neurotransmitter systems. Relatively robust evidence exists for cholinesterase inhibitors for cognitive impairment in LBD and in Parkinson's disease for antidepressants, clozapine and recently pimavanserin for psychosis. interpidine (RVT 101) and nelotanserin are currently under investigation. Non-pharmacological interventions, such as cognitive stimulation, physical exercises and neuromodulation strategies, may be useful in Parkinson's disease but have not yet been tested in dementias. Disease-modifying approaches are aimed at preventing, slowing or ameliorating the production, aggregation and deposition of pathological proteins, including immunotherapy targeting α-synuclein and an ongoing trial using ambroxol which increases glucocerebrosidase activity to lower the levels of the protein alpha-synuclein. Other disease-modifying clinical trials are using agents to augment insulin signalling, stem cell therapy, reducing amyloid pathology and gene therapy.
[Mh] Termos MeSH primário: Gerenciamento Clínico
Doença por Corpos de Lewy/diagnóstico
Doença por Corpos de Lewy/terapia
[Mh] Termos MeSH secundário: Inibidores da Colinesterase/uso terapêutico
Terapia Genética/tendências
Seres Humanos
Doença por Corpos de Lewy/imunologia
Doença de Parkinson/diagnóstico
Doença de Parkinson/imunologia
Doença de Parkinson/terapia
Piperidinas/uso terapêutico
Transplante de Células-Tronco/tendências
Ureia/análogos & derivados
Ureia/uso terapêutico
alfa-Sinucleína/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cholinesterase Inhibitors); 0 (Piperidines); 0 (alpha-Synuclein); 8W8T17847W (Urea); JZ963P0DIK (pimavanserin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1007/s11910-017-0778-2


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[PMID]:29363539
[Au] Autor:Pirmohamed M
[Ad] Endereço:Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
[Ti] Título:Nucleic acid based therapies: developing frontier for precision medicine.
[So] Source:BMJ;360:k223, 2018 01 23.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Terapia Genética/utilização
Terapia de Alvo Molecular/utilização
Ácidos Nucleicos/uso terapêutico
Medicina de Precisão/métodos
[Mh] Termos MeSH secundário: Adenoviridae/genética
Aminofenóis/uso terapêutico
Agonistas dos Canais de Cloreto/uso terapêutico
Fibrose Cística/tratamento farmacológico
Fibrose Cística/genética
Regulador de Condutância Transmembrana em Fibrose Cística/efeitos dos fármacos
Regulador de Condutância Transmembrana em Fibrose Cística/genética
Terapia Genética/economia
Genômica
Hemofilia A/classificação
Hemofilia A/tratamento farmacológico
Hemofilia A/genética
Seres Humanos
Doença dos Neurônios Motores/tratamento farmacológico
Doença dos Neurônios Motores/genética
Mutação
Oligonucleotídeos Antissenso/economia
Oligonucleotídeos Antissenso/uso terapêutico
Quinolonas/uso terapêutico
Reino Unido/epidemiologia
[Pt] Tipo de publicação:EDITORIAL
[Nm] Nome de substância:
0 (Aminophenols); 0 (CFTR protein, human); 0 (Chloride Channel Agonists); 0 (Nucleic Acids); 0 (Oligonucleotides, Antisense); 0 (Quinolones); 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator); 1Y740ILL1Z (ivacaftor)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.k223


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[PMID]:28460470
[Au] Autor:Cheng T; Song Y; Zhang Y; Zhang C; Yin J; Chi Y; Zhou D
[Ad] Endereço:Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Science, Shanghai 200031, China.
[Ti] Título:A novel oncolytic adenovirus based on simian adenovirus serotype 24.
[So] Source:Oncotarget;8(16):26871-26885, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Among the oncolytic virotherapy, an emerging treatment for tumor, adenoviruses are widely used at present in preclinical and clinical trials. Traditionally, oncolytic adenoviruses were developed based on the human adenovirus serotype 5 (AdHu5). However, AdHu5 has the drawbacks of preexisting anti-AdHu5 immunity in most populations, and extensive sequestration of Adhu5 by the liver through hexon, blood coagulation factor X (FX), and FX receptor interactions. To tackle these problems, we explored a novel oncolytic adenovirus AdC7-SP/E1A-ΔE3 for cancer treatment. AdC7-SP/E1A-ΔE3 was constructed by replacing the E1A promoter with tumor specific promoter survivin promoter and deleting E3 region using direct cloning methods based on simian adenovirus serotype 24 (namely AdC7). We showed that AdC7-SP/E1A-ΔE3 significantly killed tumor cell lines NCI-H508 and Huh7, and inhibited tumor growth in both NCI-H508 and Huh7 xenograft tumor models. Importantly, AdC7-SP/E1A-ΔE3 exhibited the antitumor efficacy via systemic administration. Mechanistically, infected cells were killed by AdC7-SP/E1A-ΔE3 via the p53-independent mitochondrial apoptosis pathway in which phosphorylation of BAD markedly declined and the expresses of Bik significantly went up. Therefore, AdC7-SP/E1A-ΔE3 is a promising candidate for liver and colon tumor treatment.
[Mh] Termos MeSH primário: Adenovirus dos Símios/classificação
Adenovirus dos Símios/genética
Vetores Genéticos/genética
Vírus Oncolíticos/genética
[Mh] Termos MeSH secundário: Proteínas E1A de Adenovirus/genética
Animais
Apoptose/genética
Linhagem Celular Tumoral
Efeito Citopatogênico Viral
Modelos Animais de Doenças
Deleção de Genes
Expressão Gênica
Engenharia Genética
Terapia Genética
Vetores Genéticos/administração & dosagem
Vetores Genéticos/efeitos adversos
Seres Humanos
Proteínas Inibidoras de Apoptose/genética
Camundongos
Mitocôndrias/genética
Terapia Viral Oncolítica
Especificidade de Órgãos/genética
Regiões Promotoras Genéticas
Sorogrupo
Transdução de Sinais
Carga Tumoral
Proteína Supressora de Tumor p53/genética
Proteína Supressora de Tumor p53/metabolismo
Replicação Viral
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adenovirus E1A Proteins); 0 (BIRC5 protein, human); 0 (Inhibitor of Apoptosis Proteins); 0 (Tumor Suppressor Protein p53)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15845


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[PMID]:29450507
[Au] Autor:Abbasi J
[Ti] Título:Hemophilia Gene Therapies Show Promise.
[So] Source:JAMA;319(6):539, 2018 Feb 13.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Terapia Genética
Hemofilia A/terapia
Hemofilia B/terapia
[Mh] Termos MeSH secundário: Vetores Genéticos
Seres Humanos
[Pt] Tipo de publicação:NEWS
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180217
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2018.0524


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[PMID]:28458031
[Au] Autor:Yin L; Yuvienco C; Montclare JK
[Ad] Endereço:Department of Chemical and Biomolecular Engineering, NYU Tandon School of Engineering, Brooklyn, NY 11201, United States.
[Ti] Título:Protein based therapeutic delivery agents: Contemporary developments and challenges.
[So] Source:Biomaterials;134:91-116, 2017 Jul.
[Is] ISSN:1878-5905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:As unique biopolymers, proteins can be employed for therapeutic delivery. They bear important features such as bioavailability, biocompatibility, and biodegradability with low toxicity serving as a platform for delivery of various small molecule therapeutics, gene therapies, protein biologics and cells. Depending on size and characteristic of the therapeutic, a variety of natural and engineered proteins or peptides have been developed. This, coupled to recent advances in synthetic and chemical biology, has led to the creation of tailor-made protein materials for delivery. This review highlights strategies employing proteins to facilitate the delivery of therapeutic matter, addressing the challenges for small molecule, gene, protein and cell transport.
[Mh] Termos MeSH primário: Materiais Biocompatíveis/química
Biopolímeros/química
Proteínas/química
[Mh] Termos MeSH secundário: Sistemas de Liberação de Medicamentos/métodos
Terapia Genética/métodos
Nanotecnologia/métodos
Engenharia de Proteínas/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biocompatible Materials); 0 (Biopolymers); 0 (Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:29384620
[Au] Autor:Zhu Y; Li D; Zhang K; Jiang L; Shi C; Fangteng J; Zheng C; Yang B; Sun H
[Ti] Título:Novel Synthesized Nanofibrous Scaffold Efficiently Delivered hBMP-2 Encoded in Adenoviral Vector to Promote Bone Regeneration.
[So] Source:J Biomed Nanotechnol;13(4):437-46, 2017 Apr.
[Is] ISSN:1550-7033
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Treatment of bone defect, especially large bone defect, is still a challenge for physicians clinically. Bone morphogenetic protein 2 (BMP-2) can induce osteoblast differentiation and promote new bone formation. Recently, nanomaterials have been widely used as a carrier to hold and deliver biomolecules, like human bone morphogenetic protein 2 gene (hBMP-2) in target cells/tissues. Most nanomethods, however, need further modification in order to work more reliably in clinical applications. Therefore, in this study, we created a novel poly(lactic-co-glycolic acid [PLGA]) nanofibrous scaffold using an electrospinning technique; then, using a lyophilization process to allow nanofibrous scaffold to adsorb hBMP-2 adenoviral vector, AdCMV-hBMP2. Results indicate that the lyophilized poly(lactic-co-glycolic acid) nanofibrous scaffold/AdCMVhBMP2 can efficiently release and transduce cells in vitro and in vivo, and secrete functional hBMP-2 to promote osteogenic differentiation in vitro, and new bone generation in vivo. Importantly, the amount of newly formed bone covered >80% of the bone defect area 8 weeks post-implantation in vivo, in which the defect could not be repaired without any treatment in general. Our data demonstrate that the lyophilized PLGA nanofibrous scaffold/AdCMV-hBMP2 created herein stably and efficiently release functional viral vector to transduce local cells, resulting in secretion of hBMP-2 and promote new bone formation in vivo. Our new nanodelivery method has potential clinical application for the repair of large bone defects.
[Mh] Termos MeSH primário: Adenoviridae/genética
Proteína Morfogenética Óssea 2/genética
Proteína Morfogenética Óssea 2/uso terapêutico
Implantes de Medicamento/administração & dosagem
Terapia Genética/métodos
Nanofibras/química
Fraturas Cranianas/terapia
[Mh] Termos MeSH secundário: Animais
Implantes de Medicamento/química
Vetores Genéticos/genética
Nanocápsulas/administração & dosagem
Nanocápsulas/química
Nanofibras/administração & dosagem
Ratos
Fraturas Cranianas/patologia
Tecidos Suporte
Transfecção/métodos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (BMP2 protein, human); 0 (Bone Morphogenetic Protein 2); 0 (Drug Implants); 0 (Nanocapsules)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE


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[PMID]:29304082
[Au] Autor:Gadek KE; Wang H; Hall MN; Sungello M; Libby A; MacLaskey D; Eckel RH; Olwin BB
[Ad] Endereço:Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado United States of America.
[Ti] Título:Striated muscle gene therapy for the treatment of lipoprotein lipase deficiency.
[So] Source:PLoS One;13(1):e0190963, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Excessive circulating triglycerides due to reduction or loss of lipoprotein lipase activity contribute to hypertriglyceridemia and increased risk for pancreatitis. The only gene therapy treatment for lipoprotein lipase deficiency decreases pancreatitis but minimally reduces hypertriglyceridemia. Synthesized in multiple tissues including striated muscle and adipose tissue, lipoprotein lipase is trafficked to blood vessel endothelial cells where it is anchored at the plasma membrane and hydrolyzes triglycerides into free fatty acids. We conditionally knocked out lipoprotein lipase in differentiated striated muscle tissue lowering striated muscle lipoprotein lipase activity causing hypertriglyceridemia. We then crossed lipoprotein lipase striated muscle knockout mice with mice possessing a conditional avian retroviral receptor gene and injected mice with either a human lipoprotein lipase retrovirus or an mCherry control retrovirus. Post-heparin plasma lipoprotein lipase activity increased for three weeks following human lipoprotein lipase retroviral infection compared to mCherry infected mice. Human lipoprotein lipase infected mice had significantly lower blood triglycerides compared to mCherry controls and were comparable to wild-type blood triglyceride levels. Thus, targeted delivery of human lipoprotein lipase into striated muscle tissue identifies a potential therapeutic target for lipoprotein lipase deficiency.
[Mh] Termos MeSH primário: Terapia Genética
Lipase Lipoproteica/genética
Músculo Estriado/patologia
[Mh] Termos MeSH secundário: Animais
Vetores Genéticos
Seres Humanos
Hipertrigliceridemia/etiologia
Camundongos
Camundongos Knockout
Músculo Estriado/enzimologia
Retroviridae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 3.1.1.34 (Lipoprotein Lipase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190963


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[PMID]:29177255
[Au] Autor:Qin C; Xia X; Pei Z; Zhang Y; Lan X
[Ad] Endereço:Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. LXL730724@hotmail.com.
[Ti] Título:Cell and gene therapy with reporter gene imaging in myocardial ischemia.
[So] Source:Hell J Nucl Med;20(3):198-203, 2017 Sep-Dec.
[Is] ISSN:1790-5427
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Reporter gene/probe systems have proved to be reliable for monitoring gene/cell therapy. We sought to evaluate whether a reporter gene/probe system, namely the human estrogen receptor ligand binding domain (hERL)/16α- F fluoro-17ß-estradiol ( F-FES), could be used for monitoring vascular endothelial growth factor (VEGF) gene expression and response to bone marrow mesenchymal stem cell (MSCs) therapy in ischemic heart disease. ANIMALS AND METHODS: Reporter gene hERL and therapeutic gene VEGF165 were linked through internal ribosome entry site (IRES), and then the recombinant adenovirus vector Adenovirus 5-hERL-IRES-VEGF (Ad5-EIV) was constructed and transfected into MSCs, and named Ad5-EIV-MSCs. Rat myocardial infarction was induced by coronary arterial branch ligature, and Ad5-EIV-MSCs were transplanted by injection into the peripheral myocardium, while non-transfected MSCs transplantation used as controls. Fluorine-18-FDG micro-PET imaging was performed to confirm myocardial infarction 1 day after surgery. Fluorine-18-FES micro-PET/CT images were acquired 2 days after Ad5-EIV-MSCs transplantation. Myocardial specimens were obtained and stained with hematoxylin-eosin (H&E) staining to verify the myocardial infarction. The expression of estrogen receptor (ER) and VEGF was detected using immunohistochemistry (IHC). RESULTS: Rat myocardial infarction models were successfully produced and confirmed by H&E staining. Images of F-FDG PET showed obvious reduced or absent uptake of F-FDG on the infarct myocardium, while uniform and well-distribution on the normal myocardium. F-FES micro-PET/CT showed the tracer notable accumulated in the apical region where Ad5-EIV-MSCs were injected with an uptake value of 0.38±0.09%ID/g, which was much higher than that of surrounding normal myocardium with nearly no uptake of F-FES (0.10±0.03%ID/g, n=5, P<0.05). In the group of non-transfected MSCs, the apical uptake was similar to that of normal myocardium. Immunohistochemistry studies demonstrated positive expression of both ER and VEGF in the involved region accompanied by active angiogenesis. CONCLUSION: This study confirmed that hERL/ F-FES could be used as a reporter gene/probe system for monitoring gene and cell therapy in the ischemic heart disease.
[Mh] Termos MeSH primário: Fluordesoxiglucose F18
Genes Reporter/genética
Terapia Genética/métodos
Transplante de Células-Tronco Mesenquimais/métodos
Isquemia Miocárdica/diagnóstico por imagem
Isquemia Miocárdica/terapia
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos
[Mh] Termos MeSH secundário: Animais
Terapia Combinada/métodos
Masculino
Compostos Radiofarmacêuticos
Ratos
Ratos Sprague-Dawley
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Radiopharmaceuticals); 0Z5B2CJX4D (Fluorodeoxyglucose F18)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1967/s002449910601



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