Barkal LJ et al. ( 2017)
Nature Communications 8 1
Microbial volatile communication in human organotypic lung models
We inhale respiratory pathogens continuously,and the subsequent signaling events between host and microbe are complex,ultimately resulting in clearance of the microbe,stable colonization of the host,or active disease. Traditional in vitro methods are ill-equipped to study these critical events in the context of the lung microenvironment. Here we introduce a microscale organotypic model of the human bronchiole for studying pulmonary infection. By leveraging microscale techniques,the model is designed to approximate the structure of the human bronchiole,containing airway,vascular,and extracellular matrix compartments. To complement direct infection of the organotypic bronchiole,we present a clickable extension that facilitates volatile compound communication between microbial populations and the host model. Using Aspergillus fumigatus,a respiratory pathogen,we characterize the inflammatory response of the organotypic bronchiole to infection. Finally,we demonstrate multikingdom,volatile-mediated communication between the organotypic bronchiole and cultures of Aspergillus fumigatus and Pseudomonas aeruginosa.
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产品号#：
05001
05021
05022
产品名：
PneumaCult™-ALI 培养基
PneumaCult™-ALI 培养基含12 mm Transwell®插件
PneumaCult™-ALI 培养基含6.5 mm Transwell®插件
Zhou T et al. (JUL 2017)
Cell stem cell
High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain.
Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date,no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids. Finally,HH and AQ inhibit ZIKV infection in adult mouse brain in vivo. Strikingly,HH suppresses viral propagation when administered to adult mice with active ZIKV infection,highlighting its therapeutic potential. Our approach highlights the power of stem cell-based screens and validation in human forebrain organoids and mouse models in identifying drug candidates for treating ZIKV infection and related neurological complications in fetal and adult patients.
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产品号#：
产品名：
Shikotra A et al. ( 2017)
Journal of immunology (Baltimore,Md. : 1950) 198 8 3307--3317
A CEACAM6-High Airway Neutrophil Phenotype and CEACAM6-High Epithelial Cells Are Features of Severe Asthma.
Severe asthma represents a major unmet clinical need; understanding the pathophysiology is essential for the development of new therapies. Using microarray analysis,we previously found three immunological clusters in asthma: Th2-high,Th17-high,and Th2/17-low. Although new therapies are emerging for Th2-high disease,identifying molecular pathways in Th2-low disease remains an important goal. Further interrogation of our previously described microarray dataset revealed upregulation of gene expression for carcinoembryonic Ag cell adhesion molecule (CEACAM) family members in the bronchi of patients with severe asthma. Our aim was therefore to explore the distribution and cellular localization of CEACAM6 using immunohistochemistry on bronchial biopsy tissue obtained from patients with mild-to-severe asthma and healthy control subjects. Human bronchial epithelial cells were used to investigate cytokine and corticosteroid in vitro regulation of CEACAM6 gene expression. CEACAM6 protein expression in bronchial biopsies was increased in airway epithelial cells and lamina propria inflammatory cells in severe asthma compared with healthy control subjects. CEACAM6 in the lamina propria was localized to neutrophils predominantly. Neutrophil density in the bronchial mucosa was similar across health and the spectrum of asthma severity,but the percentage of neutrophils expressing CEACAM6 was significantly increased in severe asthma,suggesting the presence of an altered neutrophil phenotype. CEACAM6 gene expression in cultured epithelial cells was upregulated by wounding and neutrophil elastase. In summary,CEACAM6 expression is increased in severe asthma and primarily associated with airway epithelial cells and tissue neutrophils. CEACAM6 may contribute to the pathology of treatment-resistant asthma via neutrophil and airway epithelial cell-dependent pathways.
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Efficient Derivation of Functional Human Airway Epithelium from Pluripotent Stem Cells via Temporal Regulation of Wnt Signaling.
Effective derivation of functional airway organoids from induced pluripotent stem cells (iPSCs) would provide valuable models of lung disease and facilitate precision therapies for airway disorders such as cystic fibrosis. However,limited understanding of human airway patterning has made this goal challenging. Here,we show that cyclical modulation of the canonical Wnt signaling pathway enables rapid directed differentiation of human iPSCs via an NKX2-1+progenitor intermediate into functional proximal airway organoids. We find that human NKX2-1+progenitors have high levels of Wnt activation but respond intrinsically to decreases in Wnt signaling by rapidly patterning into proximal airway lineages at the expense of distal fates. Using this directed approach,we were able to generate cystic fibrosis patient-specific iPSC-derived airway organoids with a defect in forskolin-induced swelling that is rescued by gene editing to correct the disease mutation. Our approach has many potential applications in modeling and drug screening for airway diseases.
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产品号#：
05001
05021
05022
产品名：
PneumaCult™-ALI 培养基
PneumaCult™-ALI 培养基含12 mm Transwell®插件
PneumaCult™-ALI 培养基含6.5 mm Transwell®插件
Ishikawa S et al. ( 2017)
Respiratory Research 18 1 1--11
A 3D epithelial-mesenchymal co-culture model of human bronchial tissue recapitulates multiple features of airway tissue remodeling by TGF-β1 treatment
BACKGROUND: The collagen gel contraction assay measures gel size to assess the contraction of cells embedded in collagen gel matrices. Using the assay with lung fibroblasts is useful in studying the lung tissue remodeling process in wound healing and disease development. However,the involvement of bronchial epithelial cells in this process should also be investigated. METHODS: We applied a layer of mucociliary differentiated bronchial epithelial cells onto collagen gel matrices with lung fibroblasts. This co-culture model enables direct contact between epithelial and mesenchymal cells. We stimulated the culture with transforming growth factor (TGF) beta1 as an inducer of tissue remodeling for 21 days,and measured gel size,histological changes,and expression of factors related to extracellular matrix homeostasis. RESULTS: TGF-beta1 exerted a concentration-dependent effect on collagen gel contraction and on contractile myofibroblasts in the mesenchymal collagen layer. TGF-beta1 also induced expression of the mesenchymal marker vimentin in the basal layer of the epithelium,suggesting the induction of epithelial-mesenchymal transition. In addition,the expression of various genes encoding extracellular matrix proteins was upregulated. Fibrotic tenascin-C accumulated in the sub-epithelial region of the co-culture model. CONCLUSION: Our findings indicate that TGF-beta1 can affect both epithelial and mesenchymal cells,and induce gel contraction and structural changes. Our novel in vitro co-culture model will be a useful tool for investigating the roles of epithelial cells,fibroblasts,and their interactions in the airway remodeling process.
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产品号#：
05001
05021
05022
产品名：
PneumaCult™-ALI 培养基
PneumaCult™-ALI 培养基含12 mm Transwell®插件
PneumaCult™-ALI 培养基含6.5 mm Transwell®插件
Karki R et al. (DEC 2016)
Nature
NLRC3 is an inhibitory sensor of PI3K-mTOR pathways in cancer.
NLRs (nucleotide-binding domain and leucine-rich repeats) belong to a large family of cytoplasmic sensors that regulate an extraordinarily diverse range of biological functions. One of these functions is to contribute to immunity against infectious diseases,but dysregulation of their functional activity leads to the development of inflammatory and autoimmune diseases. Cytoplasmic innate immune sensors,including NLRs,are central regulators of intestinal homeostasis. NLRC3 (also known as CLR16.2 or NOD3) is a poorly characterized member of the NLR family and was identified in a genomic screen for genes encoding proteins bearing leucine-rich repeats (LRRs) and nucleotide-binding domains. Expression of NLRC3 is drastically reduced in the tumour tissue of patients with colorectal cancer compared to healthy tissues,highlighting an undefined potential function for this sensor in the development of cancer. Here we show that mice lacking NLRC3 are hyper-susceptible to colitis and colorectal tumorigenesis. The effect of NLRC3 is most dominant in enterocytes,in which it suppresses activation of the mTOR signalling pathways and inhibits cellular proliferation and stem-cell-derived organoid formation. NLRC3 associates with PI3Ks and blocks activation of the PI3K-dependent kinase AKT following binding of growth factor receptors or Toll-like receptor 4. These findings reveal a key role for NLRC3 as an inhibitor of the mTOR pathways,mediating protection against colorectal cancer.
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产品号#：
06005
产品名：
IntestiCult™ 类器官生长培养基 (小鼠)
Bunaciu RP and Yen A (MAR 2011)
Cancer research 71 6 2371--80
Activation of the aryl hydrocarbon receptor AhR Promotes retinoic acid-induced differentiation of myeloblastic leukemia cells by restricting expression of the stem cell transcription factor Oct4.
Retinoic acid (RA) is used to treat leukemia and other cancers through its ability to promote cancer cell differentiation. Strategies to enhance the anticancer effects of RA could deepen and broaden its beneficial therapeutic applications. In this study,we describe a receptor cross-talk system that addresses this issue. RA effects are mediated by RAR/RXR receptors that we show are modified by interactions with the aryl hydrocarbon receptor (AhR),a protein functioning both as a transcription factor and a ligand-dependent adaptor in an ubiquitin ligase complex. RAR/RXR and AhR pathways cross-talk at the levels of ligand-receptor and also receptor-promoter interactions. Here,we assessed the role of AhR during RA-induced differentiation and a hypothesized convergence at Oct4,a transcription factor believed to maintain stem cell characteristics. RA upregulated AhR and downregulated Oct4 during differentiation of HL-60 promyelocytic leukemia cells. AhR overexpression in stable transfectants downregulated Oct4 and also decreased ALDH1 activity,another stem cell-associated factor,enhancing RA-induced differentiation as indicated by cell differentiation markers associated with early (CD38 and CD11b) and late (neutrophilic respiratory burst) responses. AhR overexpression also increased levels of activated Raf1,which is known to help propel RA-induced differentiation. RNA interference-mediated knockdown of Oct4 enhanced RA-induced differentiation and G(0) cell-cycle arrest relative to parental cells. Consistent with the hypothesized importance of Oct4 downregulation for differentiation,parental cells rendered resistant to RA by biweekly high RA exposure displayed elevated Oct4 levels that failed to be downregulated. Together,our results suggested that therapeutic effects of RA-induced leukemia differentiation depend on AhR and its ability to downregulate the stem cell factor Oct4.
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产品号#：
01700
01705
01701
01702
07912
产品名：
ALDEFLUOR™ 试剂盒
ALDEFLUOR™ DEAB试剂, 1.5 mM, 1 mL
ALDEFLUOR™检测缓冲液
胶原酶/透明质酸酶
Pond AC et al. ( 2013)
Stem cells (Dayton,Ohio) 31 1 10.1002/stem.1266
Fibroblast Growth Factor Receptor Signaling Is Essential for Normal Mammary Gland Development and Stem Cell Function
Fibroblast growth factor (FGF) signaling plays an important role in embryonic stem cells and adult tissue homeostasis,but the function of FGFs in mammary gland stem cells is less well defined. Both FGFR1 and FGFR2 are expressed in basal and luminal mammary epithelial cells (MECs),suggesting that together they might play a role in mammary gland development and stem cell dynamics. Previous studies have demonstrated that the deletion of FGFR2 resulted only in transient developmental defects in branching morphogenesis. Using a conditional deletion strategy,we investigated the consequences of FGFR1 deletion alone and then the simultaneous deletion of both FGFR1 and FGFR2 in the mammary epithelium. FGFR1 deletion using a keratin 14 promoter-driven Cre-recombinase resulted in an early,yet transient delay in development. However,no reduction in functional outgrowth potential was observed following limiting dilution transplantation analysis. In contrast,a significant reduction in outgrowth potential was observed upon the deletion of both FGFR1 and FGFR2 in MECs using adenovirus-Cre. Additionally,using a fluorescent reporter mouse model to monitor Cre-mediated recombination,we observed a competitive disadvantage following transplantation of both FGFR1/R2-null MECs,most prominently in the basal epithelial cells. This correlated with the complete loss of the mammary stem cell repopulating population in the FGFR1/R2-attenuated epithelium. FGFR1/R2-null MECs were partially rescued in chimeric outgrowths containing wild-type MECs,suggesting the potential importance of paracrine mechanisms involved in the maintenance of the basal epithelial stem cells. These studies document the requirement for functional FGFR signaling in mammary stem cells during development.
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产品号#：
19758
60099
60099.1
60099AD
60099AD.1
60099AZ
60099AZ.1
60099BT
60099BT.1
60099FI
60099FI.1
60099PE
60099PE.1
60099PS
60099PS.1
60037
60037AD
60037AD.1
60037AZ
60037AZ.1
60037BT
60037BT.1
60037FI
60037FI.1
60037PE
60037PE.1
60037PB
60037PB.1
产品名：
抗小鼠CD24抗体，clone M1/69
抗小鼠CD24抗体，clone M1/69
抗小鼠CD24抗体，clone M1/69，Alexa Fluor® 488
抗小鼠CD24抗体，clone M1/69，Alexa Fluor® 488
抗小鼠CD24抗体，clone M1/69，APC
抗小鼠CD24抗体，clone M1/69，Biotin
抗小鼠CD24抗体，clone M1/69，Biotin
抗小鼠CD24抗体，clone M1/69，PE
抗小鼠CD24抗体，clone M1/69，PE
抗小鼠CD24抗体，clone M1/69，PerCP-Cy5.5
抗小鼠CD24抗体，clone M1/69，PerCP-Cy5.5
抗小鼠CD49f抗体，clone GoH3
抗小鼠CD49f抗体，clone GoH3，Alexa Fluor® 488
抗小鼠CD49f抗体，clone GoH3，Alexa Fluor® 488
抗小鼠CD49f抗体，clone GoH3，APC
抗小鼠CD49f抗体，clone GoH3，Biotin
抗小鼠CD49f抗体，clone GoH3，FITC
抗小鼠CD49f抗体，clone GoH3，PE
抗小鼠CD49f抗体，clone GoH3，PE
抗小鼠CD49f抗体，clone GoH3，Pacific Blue™
抗小鼠CD49f抗体，clone GoH3，Pacific Blue™
Pino CJ et al. (FEB 2013)
Nephrology,dialysis,transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 28 2 296--302
Cell-based approaches for the treatment of systemic inflammation.
Acute and chronic solid organ failures are costly disease processes with high mortality rates. Inflammation plays a central role in both acute and chronic organ failure,including heart,lung and kidney. In this regard,new therapies for these disorders have focused on inhibiting the mediators of inflammation,including cytokines and free radicals,with little or no success in clinical studies. Recent novel treatment strategies have been directed to cell-based rather than mediator-based approaches,designed to immunomodulate the deleterious effects of inflammation on organ function. One approach,cell therapy,replaces cells that were damaged in the acute or chronic disease process with stem/progenitor technology,to rebalance excessive inflammatory states. As an example of this approach,the use of an immunomodulatory role of renal epithelial progenitor cells to treat acute renal failure (ARF) and multiorgan failure arising from acute kidney injury is reviewed. A second therapeutic pathway,cell processing,does not incorporate stem/progenitor cells in the device,but rather biomimetic materials that remove and modulate the primary cellular components,which promote the worsening organ tissue injury associated with inflammation. The use of an immunomodulating leukocyte selective cytopheretic inhibitory device is also reviewed as an example of this cell processing approach. Both of these unconventional strategies have shown early clinical efficacy in pilot clinical trials and may transform the therapeutic approach to organ failure disorders.
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产品号#：
07930
07931
07940
07955
07956
07959
07954
100-1061
07952
产品名：
CryoStor® CS10
CryoStor® CS10
CryoStor® CS10
CryoStor® CS10
CryoStor® CS10
CryoStor® CS10
CryoStor® CS10
Ketola K et al. (DEC 2010)
Molecular cancer therapeutics 9 12 3175--85
Monensin is a potent inducer of oxidative stress and inhibitor of androgen signaling leading to apoptosis in prostate cancer cells.
Current treatment options for advanced and hormone refractory prostate cancer are limited and responses to commonly used androgen pathway inhibitors are often unsatisfactory. Our recent results indicated that sodium ionophore monensin is one of the most potent and cancer-specific inhibitors in a systematic sensitivity testing of most known drugs and drug-like molecules in a panel of prostate cancer cell models. Because monensin has been extensively used in veterinary applications to build muscle mass in cattle,the link to prostate cancer and androgen signaling was particularly interesting. Here,we showed that monensin effects at nanomolar concentrations are linked to induction of apoptosis and potent reduction of androgen receptor mRNA and protein in prostate cancer cells. Monensin also elevated intracellular oxidative stress in prostate cancer cells as evidenced by increased generation of intracellular reactive oxygen species and by induction of a transcriptional profile characteristic of an oxidative stress response. Importantly,the antiproliferative effects of monensin were potentiated by combinatorial treatment with the antiandrogens and antagonized by antioxidant vitamin C. Taken together,our results suggest monensin as a potential well-tolerated,in vivo compatible drug with strong proapoptotic effects in prostate cancer cells,and synergistic effects with antiandrogens. Moreover,our data suggest a general strategy by which the effects of antiandrogens could be enhanced by combinatorial administration with agents that increase oxidative stress in prostate cancer cells.
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EasySep™小鼠TIL（CD45）正选试剂盒
沪公网安备31010102008431号