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  1 / 39339 MEDLINE  
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[PMID]:29335532
[Au] Autor:Brasko C; Smith K; Molnar C; Farago N; Hegedus L; Balind A; Balassa T; Szkalisity A; Sukosd F; Kocsis K; Balint B; Paavolainen L; Enyedi MZ; Nagy I; Puskas LG; Haracska L; Tamas G; Horvath P
[Ad] Endereço:University of Szeged, Szeged, Hungary Közép fasor 52, 6726, Szeged, Hungary.
[Ti] Título:Intelligent image-based in situ single-cell isolation.
[So] Source:Nat Commun;9(1):226, 2018 01 15.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Quantifying heterogeneities within cell populations is important for many fields including cancer research and neurobiology; however, techniques to isolate individual cells are limited. Here, we describe a high-throughput, non-disruptive, and cost-effective isolation method that is capable of capturing individually targeted cells using widely available techniques. Using high-resolution microscopy, laser microcapture microscopy, image analysis, and machine learning, our technology enables scalable molecular genetic analysis of single cells, targetable by morphology or location within the sample.
[Mh] Termos MeSH primário: Separação Celular/métodos
Processamento de Imagem Assistida por Computador/métodos
Microscopia Confocal/métodos
Análise de Célula Única/métodos
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Perfilação da Expressão Gênica
Seres Humanos
Aprendizado de Máquina
Células Piramidais/citologia
Células Piramidais/metabolismo
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[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:180117
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02628-4


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[PMID]:29360826
[Au] Autor:Moreno-Amador JL; Téllez N; Marin S; Aloy-Reverté C; Semino C; Nacher M; Montanya E
[Ad] Endereço:Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.
[Ti] Título:Epithelial to mesenchymal transition in human endocrine islet cells.
[So] Source:PLoS One;13(1):e0191104, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: ß-cells undergo an epithelial to mesenchymal transition (EMT) when expanded in monolayer culture and give rise to highly proliferative mesenchymal cells that retain the potential to re-differentiate into insulin-producing cells. OBJECTIVE: To investigate whether EMT takes place in the endocrine non-ß cells of human islets. METHODOLOGY: Human islets isolated from 12 multiorgan donors were dissociated into single cells, purified by magnetic cell sorting, and cultured in monolayer. RESULTS: Co-expression of insulin and the mesenchymal marker vimentin was identified within the first passage (p1) and increased subsequently (insulin+vimentin+ 7.2±6% at p1; 43±15% at p4). The endocrine non-ß-cells did also co-express vimentin (glucagon+vimentin+ 59±1.5% and 93±6%, somatostatin+vimentin+ 16±9.4% and 90±10% at p1 and p4 respectively; PP+vimentin+ 74±14% at p1; 88±12% at p2). The percentage of cells expressing only endocrine markers was progressively reduced (0.6±0.2% insulin+, 0.2±0.1% glucagon+, and 0.3±0.2% somatostatin+ cells at p4, and 0.7±0.3% PP+ cells at p2. Changes in gene expression were also indicated of EMT, with reduced expression of endocrine markers and the epithelial marker CDH-1 (p<0.01), and increased expression of mesenchymal markers (CDH-2, SNAI2, ZEB1, ZEB2, VIM, NT5E and ACTA2; p<0.05). Treatment with the EMT inhibitor A83-01 significantly reduced the percentage of co-expressing cells and preserved the expression of endocrine markers. CONCLUSIONS: In adult human islets, all four endocrine islet cell types undergo EMT when islet cells are expanded in monolayer conditions. The presence of EMT in all islet endocrine cells could be relevant to design of strategies aiming to re-differentiate the expanded islet cells towards a ß-cell phenotype.
[Mh] Termos MeSH primário: Transição Epitelial-Mesenquimal
Ilhotas Pancreáticas/citologia
[Mh] Termos MeSH secundário: Adulto
Biomarcadores/metabolismo
Morte Celular
Separação Celular
Células Cultivadas
Seres Humanos
Ilhotas Pancreáticas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers)
[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:180124
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191104


  3 / 39339 MEDLINE  
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[PMID]:29265876
[Au] Autor:Wu CP; Wu P; Zhao HF; Liu WL; Li WP
[Ad] Endereço:1 Department of Neurosurgery, Shenzhen Second People's Hospital, Clinical Medicine College of Anhui Medical University , Shenzhen, China .
[Ti] Título:Clinical Applications of and Challenges in Single-Cell Analysis of Circulating Tumor Cells.
[So] Source:DNA Cell Biol;37(2):78-89, 2018 Feb.
[Is] ISSN:1557-7430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Technological advancements in next-generation sequencing are continually changing the landscape of genomic, transcriptomic, and epigenetic research at the single-cell level. These technologies have been used to detect and analyze circulating tumor cells (CTCs) at the molecular level and provide a new approach for the management of cancer patients. A series of unanticipated discoveries, including the heterogeneity of cancer cell populations, new driver mutations responsible for the resistance of tumors to chemotherapy, and the mechanism of tumor metastasis, have been made using single CTC sequencing. CTC detection has been used in cancer diagnosis and monitoring and in determining the prognosis of cancer patients. Traditional treatment for cancer patients is universal and does not consider genetic variations among patients, but in the era of precision medicine, giving the right drug to the right patient at the right time is the core philosophy. In this study, we review the fundamental principles of CTC isolation and single-cell sequencing and discuss recent progress in their application in both basic research and clinical fields and describe the current challenges.
[Mh] Termos MeSH primário: Neoplasias/patologia
Células Neoplásicas Circulantes/efeitos dos fármacos
Análise de Célula Única
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Separação Celular
Resistência a Medicamentos Antineoplásicos
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Neoplasias/tratamento farmacológico
Células-Tronco Neoplásicas/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1089/dna.2017.3981


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[PMID]:29265183
[Au] Autor:Kulkeaw K; Inoue T; Ishitani T; Nakanishi Y; Zon LI; Sugiyama D
[Ad] Endereço:Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
[Ti] Título:Purification of zebrafish erythrocytes as a means of identifying a novel regulator of haematopoiesis.
[So] Source:Br J Haematol;180(3):420-431, 2018 02.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Zebrafish embryos are useful to study haematopoietic gene function in vertebrates, although lack of antibodies to zebrafish proteins has limited the purification of specific cell populations. Here, we purified primitive zebrafish erythrocytes using 1, 5-bis{[2-(di-methylamino)ethyl]amino}-4, 8-dihydroxyanthracene-9, 10-dione (DRAQ5 ), a DNA-staining fluorescent dye. At 48-h post-fertilization, we sorted small-sized cells from embryos using forward scatter and found that they consisted of DRAQ5 and DRAQ5 populations. DRAQ5 cells contained haemoglobin, lacked myeloperoxidase activity and expressed high levels of embryonic globin (hbae3 and hbbe1.1) mRNA, all characteristics of primitive erythrocytes. Following DRAQ5 analysis of gata1:dsRed transgenic embryos, we purified primitive DRAQ5 dsRed+ erythrocytes from haematopoietic progenitor cells. Using this method, we identified docking protein 2 (Dok2) as functioning in differentiation of primitive erythrocytes. We conclude that DRAQ5 -based flow cytometry enables purification of primitive zebrafish erythrocytes.
[Mh] Termos MeSH primário: Eritrócitos/citologia
Eritrócitos/metabolismo
Hematopoese
[Mh] Termos MeSH secundário: Animais
Biomarcadores
Separação Celular/métodos
Citometria de Fluxo
Regulação da Expressão Gênica
Hematopoese/genética
Imunofenotipagem
Especificidade de Órgãos/genética
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.15048


  5 / 39339 MEDLINE  
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[PMID]:29254293
[Au] Autor:Di Spigna G; Iannone M; Ladogana P; Salzano S; Ventre M; Covelli B; De Marinis E; Postiglione L
[Ad] Endereço:Department of Translational Medical Sciences, University of Naples “Federico II”, Naples, Italy.
[Ti] Título:Human cardiac multipotent adult stem cells in 3D matrix: new approach of tissue engineering in cardiac regeneration post-infarction.
[So] Source:J Biol Regul Homeost Agents;31(4):911-921, 2017 Oct-Dec.
[Is] ISSN:0393-974X
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:Myocardial infarction is the leading cause of morbidity and mortality in developed countries. It causes a left ventricular dysfunction, mainly due to the loss of functional tissue, resulting in heart failure. New therapies are being developed, using a tissue engineering approach, with the ultimate goal of restoring cardiac function by regenerating and repairing the damaged myocardium. In the present study we investigated the behaviour of a specific population of c-kit positive human cardiac stem cells, called Multipotent Adult Stem Cells (MASCs), grown within three-dimensional collagen scaffolds (3D), to establish whether they could be used in post-infarction cardiac regeneration. We also evaluated the expression levels of the Granulocyte Macrophage-Colony Stimulating Factor Receptor (GM-CSFR) and endoglin, a component of the Transforming Growth Factor beta (TGF-ß) receptor complex. Finally, we also evaluated the expression of the α2ß1integrin. MASCs cultured within 3D collagen matrices are able to proliferate and migrate even in the absence of chemotactic agents and express high levels of factors involved in cell proliferation and migration, such as GM-CSFRα chain and integrins. They therefore represent a promising approach to tissue engineering aimed to restore cardiac function. Our results also suggest a role of GM-CSF in cell proliferation, while TGF-ß does not seem to be relevant.
[Mh] Termos MeSH primário: Células-Tronco Adultas/citologia
Células-Tronco Multipotentes/citologia
Engenharia Tecidual/métodos
Tecidos Suporte
[Mh] Termos MeSH secundário: Células-Tronco Adultas/metabolismo
Técnicas de Cultura de Células
Movimento Celular
Proliferação Celular
Separação Celular
Colágeno/química
Endoglina/genética
Endoglina/metabolismo
Expressão Gênica
Seres Humanos
Integrina alfa2beta1/genética
Integrina alfa2beta1/metabolismo
Células-Tronco Multipotentes/metabolismo
Infarto do Miocárdio
Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética
Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo
Fator de Crescimento Transformador beta/genética
Fator de Crescimento Transformador beta/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ENG protein, human); 0 (Endoglin); 0 (Integrin alpha2beta1); 0 (Receptors, Granulocyte-Macrophage Colony-Stimulating Factor); 0 (Transforming Growth Factor beta); 9007-34-5 (Collagen)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE


  6 / 39339 MEDLINE  
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[PMID]:29254292
[Au] Autor:Cantore S; Ballini A; De Vito D; Martelli FS; Georgakopoulos I; Almasri M; Dibello V; Altini V; Farronato G; Dipalma G; Farronato D; Inchingolo F
[Ad] Endereço:Department of Interdisciplinary Medicine, School of Medicine, University of Bari Aldo Moro, Bari, Italy.
[Ti] Título:Characterization of human apical papilla-derived stem cells.
[So] Source:J Biol Regul Homeost Agents;31(4):901-910, 2017 Oct-Dec.
[Is] ISSN:0393-974X
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:Dental tissues represent an alternative and promising source of post-natal Mesenchymal stem cells (MSCs) for tissue engineering. Furthermore, dental stem cells from apical papilla (SCAPs) cells can be obtained from the wisdom tooth which is unnecessary for human masticatory function and frequently extracted for orthodontic reasons or dysodontiasis. More precisely, apical papilla is the immature, mostly uncalcified, precursor of the tooth root, therefore is composed of more undifferentiated cells than dental pulp. In addition, tooth extraction, especially by piezosurgery technique, can be considered less invasive in comparison to bone marrow or other tissues biopsy. Our work is aimed to investigate the safety of and predictable procedure on surgical immature third molar extraction and to provide new insight on SCAP research for future biomedical applications. The isolated cells were examined for stem cell properties by analyzing their colony-forming efficiency, differentiation characteristics and the expression of MSC markers.
[Mh] Termos MeSH primário: Polpa Dentária/citologia
Células Mesenquimais Estromais/citologia
Osteogênese/genética
Raiz Dentária/citologia
[Mh] Termos MeSH secundário: Adolescente
Biomarcadores/metabolismo
Diferenciação Celular
Proliferação Celular
Separação Celular
Criança
Ensaio de Unidades Formadoras de Colônias
Polpa Dentária/metabolismo
Feminino
Expressão Gênica
Seres Humanos
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo
Masculino
Células Mesenquimais Estromais/metabolismo
Dente Molar/cirurgia
Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética
Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo
Engenharia Tecidual
Extração Dentária
Raiz Dentária/metabolismo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Insulin-Like Growth Factor Binding Proteins); 0 (JunB protein, human); 0 (NR4A2 protein, human); 0 (Nuclear Receptor Subfamily 4, Group A, Member 2); 0 (Transcription Factors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE


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[PMID]:29342188
[Au] Autor:Deveza L; Ortinau L; Lei K; Park D
[Ad] Endereço:Department of Orthopaedic Surgery, Baylor College of Medicine, Houston, TX, United States of America.
[Ti] Título:Comparative analysis of gene expression identifies distinct molecular signatures of bone marrow- and periosteal-skeletal stem/progenitor cells.
[So] Source:PLoS One;13(1):e0190909, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Periosteum and bone marrow (BM) both contain skeletal stem/progenitor cells (SSCs) that participate in fracture repair. However, the functional difference and selective regulatory mechanisms of SSCs in different locations are unknown due to the lack of specific markers. Here, we report a comprehensive gene expression analysis of bone marrow SSCs (BM-SSCs), periosteal SSCs (P-SSCs), and more differentiated osteoprogenitors by using reporter mice expressing Interferon-inducible Mx1 and NestinGFP, previously known SSC markers. We first defined that the BM-SSCs can be enriched by the combination of Mx1 and NestinGFP expression, while endogenous P-SSCs can be isolated by positive selection of Mx1, CD105 and CD140a (known SSC markers) combined with the negative selection of CD45, CD31, and osteocalcinGFP (a mature osteoblast marker). Comparative gene expression analysis with FACS-sorted BM-SSCs, P-SSCs, Osterix+ preosteoblasts, CD51+ stroma cells and CD45+ hematopoietic cells as controls revealed that BM-SSCs and P-SSCs have high similarity with few potential differences without statistical significance. We also found that CD51+ cells are highly heterogeneous and have little overlap with SSCs. This was further supported by the microarray cluster analysis, where the two SSC populations clustered together but are separate from the CD51+ cells. However, when comparing SSC population to controls, we found several genes that are uniquely upregulated in endogenous SSCs. Amongst these genes, we found KDR (aka Flk1 or VEGFR2) to be most interesting and discovered that it is highly and selectively expressed in P-SSCs. This finding suggests that endogenous P-SSCs are functionally very similar to BM-SSCs with undetectable significant differences in gene expression but there are distinct molecular signatures in P-SSCs, which can be useful to specify P-SSC subset in vivo.
[Mh] Termos MeSH primário: Células da Medula Óssea/metabolismo
Expressão Gênica
Periósteo/metabolismo
Células-Tronco/metabolismo
[Mh] Termos MeSH secundário: Animais
Células da Medula Óssea/citologia
Separação Celular
Citometria de Fluxo
Marcadores Genéticos
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Periósteo/citologia
Células-Tronco/citologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Genetic Markers)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190909


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[PMID]:29293622
[Au] Autor:Ma Y; Dawicki W; Zhang X; Gordon JR
[Ad] Endereço:Division of Respirology, Critical Care and Sleep Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
[Ti] Título:Contributions of direct versus indirect mechanisms for regulatory dendritic cell suppression of asthmatic allergen-specific IgG1 antibody responses.
[So] Source:PLoS One;13(1):e0190414, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:IL-10-differentiated dendritic cells (DC10) can reverse the asthma phenotype in mice, but how they suppress the asthmatic B cell response is unclear. Herein we assessed the mechanism(s) by which DC10 and DC10-induced Treg affect IgG1 production in asthma. We observed a rapid decline in lung-resident OVA-specific IgG1-secreting B cells on cessation of airway allergen challenge, and intraperitoneal DC10 therapy did not amplify that (p>0.05). It did however increase the loss of IgG1-B cells from the bone marrow (by 45+/-7.2%; p≤0.01) and spleen (by 65+/-17.8%; p≤0.05) over 2 wk. Delivery of OVA-loaded DC10 directly into the airways of asthmatic mice decreased the lung IgG1 B cell response assessed 2 dy later by 33+/-9.7% (p≤0.01), while their co-culture with asthmatic lung cell suspensions reduced the numbers of IgG1-secreting cells by 56.5+/-9.7% (p≤0.01). This effect was dependent on the DC10 carrying intact allergen on their cell surface; DC10 that had phagocytosed and fully processed their allergen were unable to suppress B cell responses, although they did suppress asthmatic Th2 cell responses. We had shown that therapeutic delivery of DC10-induced Treg can effectively suppress asthmatic T and B cell (IgE and IgG1) responses; herein CD4+ cells or Treg from the lungs of DC10-treated OVA-asthmatic mice suppressed in vitro B cell IgG1 production by 52.2+/-8.7% (p≤0.001) or 44.6+/-12.2% (p≤0.05), respectively, but delivery of DC10-induced Treg directly into the airways of asthmatic mice had no discernible impact over 2 dy on the numbers of lung IgG1-secreting cells (p≥0.05). In summary, DC10 treatment down-regulates OVA-specific B cell responses of asthmatic mice. While DC10 that carry intact allergen on their cell surface can dampen this response, DC10-induced Treg are critical for full realization of this outcome. This suggests that infectious tolerance is an essential element in regulatory DC control of the B cell response in allergic asthma.
[Mh] Termos MeSH primário: Alérgenos/imunologia
Asma/imunologia
Imunoglobulina G/imunologia
Linfócitos T Reguladores/imunologia
[Mh] Termos MeSH secundário: Animais
Separação Celular
Ensaio de Imunoadsorção Enzimática
Feminino
Citometria de Fluxo
Camundongos
Camundongos Endogâmicos BALB C
Ovalbumina/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Allergens); 0 (Immunoglobulin G); 9006-59-1 (Ovalbumin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190414


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[PMID]:29309789
[Au] Autor:Ke M; Cai S; Zou M; Zhao Y; Li B; Chen S; Chen L
[Ad] Endereço:College of Bioengineering, Chongqing University, Chongqing, 400044, China.
[Ti] Título:A microfluidic device for study of the effect of tumor vascular structures on the flow field and HepG2 cellular flow behaviors.
[So] Source:Biochem Biophys Res Commun;496(1):238-243, 2018 01 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To build a microfluidic device with various morphological features of the tumor vasculature for study of the effects of tumor vascular structures on the flow field and tumor cellular flow behaviors. The designed microfluidic device was able to approximatively simulate the in vivo structures of tumor vessels and the flow within it. In this models, the influences of the angle of bifurcation, the number of branches, and the narrow channels on the flow field and the influence of vorticity on the retention of HepG2 cells were significant. Additionally, shear stress below physiological conditions of blood circulation has considerable effect on the formation of the lumen-like structures (LLSs) of HepG2 cells. These results can provide some data and reference in the understanding of the interaction between hemorheological properties and tumor vascular structures in solid tumors.
[Mh] Termos MeSH primário: Reatores Biológicos
Técnicas de Cultura de Células/instrumentação
Separação Celular/instrumentação
Células Hep G2/fisiologia
Dispositivos Lab-On-A-Chip
Neovascularização Patológica/fisiopatologia
[Mh] Termos MeSH secundário: Desenho de Equipamento
Análise de Falha de Equipamento
Células Hep G2/patologia
Seres Humanos
Neovascularização Patológica/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


  10 / 39339 MEDLINE  
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[PMID]:28749819
[Au] Autor:Boylan JM; Francois-Vaughan H; Gruppuso PA; Sanders JA
[Ad] Endereço:1 Department of Pediatrics, Rhode Island Hospital and Brown University, Providence, RI. 2 Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI. 3 Department of Pathology and Laboratory Medicine, Brown University, Providence, RI.
[Ti] Título:Engraftment and Repopulation Potential of Late Gestation Fetal Rat Hepatocytes.
[So] Source:Transplantation;101(10):2349-2359, 2017 10.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The limited availability of donor organs has led to a search for alternatives to liver transplantation to restore liver function and bridge patients to transplantation. We have shown that the proliferation of late gestation (embryonic day 19) fetal rat hepatocytes is mitogen-independent and that mechanisms regulating mRNA translation, cell cycle progression, and gene expression differ from those of adult rat hepatocytes. In the present study, we investigated whether E19 fetal hepatocytes can engraft and repopulate an injured adult liver. METHODS: Fetal hepatocytes were isolated using a monoclonal antibody against a hepatic surface protein, leucine amino peptidase (LAP). LAP+ and LAP- fractions were analyzed by immunofluorescence and microarray. Immunopurified E19 liver cells from DPPIV+ rats were transplanted via splenic injection into partial hepatectomized DPPIV- rats that had been pretreated with mitomycin C. RESULTS: More than a third of LAP+ fetal hepatocytes expressed ductal markers. Transcriptomic analysis revealed that these dual-expressing cells represent a population of less well-differentiated hepatocytes. Upon transplantation, LAP+ late gestation fetal hepatocytes formed hepatic, endothelial, and ductal colonies within 1 month. By 10 months, colonies derived from LAP+ cells increased so that up to 35% of the liver was repopulated by donor-derived cells. CONCLUSIONS: Late gestation fetal hepatocytes, despite being far along in the differentiation process, possess the capacity for extensive liver repopulation. This is likely related to the unexpected presence of a significant proportion of hepatocyte marker-positive cells maintaining a less well-differentiated phenotype.
[Mh] Termos MeSH primário: Proliferação Celular
Hepatócitos/transplante
Regeneração Hepática
Transplante de Fígado/métodos
Fígado/embriologia
[Mh] Termos MeSH secundário: Animais
Biomarcadores/metabolismo
Diferenciação Celular
Linhagem da Célula
Separação Celular/métodos
Sobrevivência Celular
Células Cultivadas
Feminino
Regulação da Expressão Gênica no Desenvolvimento
Idade Gestacional
Sobrevivência de Enxerto
Hepatectomia
Hepatócitos/metabolismo
Fenótipo
Gravidez
Ratos Endogâmicos F344
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Biomarkers)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001882



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