Product Information

文献

Capucha T et al. (JAN 2018) The Journal of experimental medicine

Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation.

Mucosal Langerhans cells (LCs) originate from pre-dendritic cells and monocytes. However,the mechanisms involved in their in situ development remain unclear. Here,we demonstrate that the differentiation of murine mucosal LCs is a two-step process. In the lamina propria,signaling via BMP7-ALK3 promotes translocation of LC precursors to the epithelium. Within the epithelium,TGF-β1 finalizes LC differentiation,and ALK5 is crucial to this process. Moreover,the local microbiota has a major impact on the development of mucosal LCs,whereas LCs in turn maintain mucosal homeostasis and prevent tissue destruction. These results reveal the differential and sequential role of TGF-β1 and BMP7 in LC differentiation and highlight the intimate interplay of LCs with the microbiota. View Publication

产品号#：

19861

19861RF

产品名：

EasySep™小鼠单核细胞分选试剂盒

RoboSep™ 小鼠单核细胞分选试剂盒

文献

Berer K et al. (OCT 2017) Proceedings of the National Academy of Sciences of the United States of America 114 40 10719--10724

Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice.

There is emerging evidence that the commensal microbiota has a role in the pathogenesis of multiple sclerosis (MS),a putative autoimmune disease of the CNS. Here,we compared the gut microbial composition of 34 monozygotic twin pairs discordant for MS. While there were no major differences in the overall microbial profiles,we found a significant increase in some taxa such as Akkermansia in untreated MS twins. Furthermore,most notably,when transplanted to a transgenic mouse model of spontaneous brain autoimmunity,MS twin-derived microbiota induced a significantly higher incidence of autoimmunity than the healthy twin-derived microbiota. The microbial profiles of the colonized mice showed a high intraindividual and remarkable temporal stability with several differences,including Sutterella,an organism shown to induce a protective immunoregulatory profile in vitro. Immune cells from mouse recipients of MS-twin samples produced less IL-10 than immune cells from mice colonized with healthy-twin samples. IL-10 may have a regulatory role in spontaneous CNS autoimmunity,as neutralization of the cytokine in mice colonized with healthy-twin fecal samples increased disease incidence. These findings provide evidence that MS-derived microbiota contain factors that precipitate an MS-like autoimmune disease in a transgenic mouse model. They hence encourage the detailed search for protective and pathogenic microbial components in human MS. View Publication

产品号#：

15022

15062

产品名：

RosetteSep™人CD4+ T细胞富集抗体混合物

文献

Bai M et al. ( 2017) Blood 130 19 2092--2100

CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation.

CD177 is a glycosylphosphatidylinositol (GPI)-anchored protein expressed by a variable proportion of human neutrophils that mediates surface expression of the antineutrophil cytoplasmic antibody antigen proteinase 3. CD177 associates with β2 integrins and recognizes platelet endothelial cell adhesion molecule 1 (PECAM-1),suggesting a role in neutrophil migration. However,CD177pos neutrophils exhibit no clear migratory advantage in vivo,despite interruption of in vitro transendothelial migration by CD177 ligation. We sought to understand this paradox. Using a PECAM-1-independent transwell system,we found that CD177pos and CD177neg neutrophils migrated comparably. CD177 ligation selectively impaired migration of CD177pos neutrophils,an effect mediated through immobilization and cellular spreading on the transwell membrane. Correspondingly,CD177 ligation enhanced its interaction with β2 integrins,as revealed by fluorescence lifetime imaging microscopy,leading to integrin-mediated phosphorylation of Src and extracellular signal-regulated kinase (ERK). CD177-driven cell activation enhanced surface β2 integrin expression and affinity,impaired internalization of integrin attachments,and resulted in ERK-mediated attenuation of chemokine signaling. We conclude that CD177 signals in a β2 integrin-dependent manner to orchestrate a set of activation-mediated mechanisms that impair human neutrophil migration. View Publication

产品号#：

19666

产品名：

EasySep™ Direct人中性粒细胞分选试剂盒

文献

Alculumbre SG et al. (JAN 2018) Nature immunology 19 1 63--75

Diversification of human plasmacytoid predendritic cells in response to a single stimulus.

Innate immune cells adjust to microbial and inflammatory stimuli through a process termed environmental plasticity,which links a given individual stimulus to a unique activated state. Here,we report that activation of human plasmacytoid predendritic cells (pDCs) with a single microbial or cytokine stimulus triggers cell diversification into three stable subpopulations (P1-P3). P1-pDCs (PD-L1+CD80-) displayed a plasmacytoid morphology and specialization for type I interferon production. P3-pDCs (PD-L1-CD80+) adopted a dendritic morphology and adaptive immune functions. P2-pDCs (PD-L1+CD80+) displayed both innate and adaptive functions. Each subpopulation expressed a specific coding- and long-noncoding-RNA signature and was stable after secondary stimulation. P1-pDCs were detected in samples from patients with lupus or psoriasis. pDC diversification was independent of cell divisions or preexisting heterogeneity within steady-state pDCs but was controlled by a TNF autocrine and/or paracrine communication loop. Our findings reveal a novel mechanism for diversity and division of labor in innate immune cells. View Publication

产品号#：

19062

19062RF

19251

19251RF

产品名：

EasySep™人浆细胞样DC富集试剂盒

RoboSep™ 人浆细胞样DC富集试剂盒含滤芯吸头

EasySep™人Pan-DC预富集试剂盒

RoboSep™ 人Pan-DC预富集试剂盒含滤芯吸头

文献

Zhang Y et al. ( 2018) Nature communications 9 1 6

Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity.

Immunostimulatory agents such as agonistic anti-CD137 and interleukin (IL)-2 generate effective anti-tumor immunity but also elicit serious toxicities,hampering their clinical application. Here we show that combination therapy with anti-CD137 and an IL-2-Fc fusion achieves significant initial anti-tumor activity,but also lethal immunotoxicity deriving from stimulation of circulating leukocytes. To overcome this toxicity,we demonstrate that anchoring IL-2 and anti-CD137 on the surface of liposomes allows these immune agonists to rapidly accumulate in tumors while lowering systemic exposure. In multiple tumor models,immunoliposome delivery achieves anti-tumor activity equivalent to free IL-2/anti-CD137 but with the complete absence of systemic toxicity. Immunoliposomes stimulated tumor infiltration by cytotoxic lymphocytes,cytokine production,and granzyme expression,demonstrating equivalent immunostimulatory effects to the free drugs in the local tumor microenvironment. Thus,surface-anchored particle delivery may provide a general approach to exploit the potent stimulatory activity of immune agonists without debilitating systemic toxicities. View Publication

文献

Yang K et al. (JAN 2018) Biosensors & bioelectronics 99 259--267

Mkit: A cell migration assay based on microfluidic device and smartphone.

Mobile sensing based on the integration of microfluidic device and smartphone,so-called MS2 technology,has enabled many applications over recent years,and continues to stimulate growing interest in both research communities and industries. In particular,it has been envisioned that MS2 technology can be developed for various cell functional assays to enable basic research and clinical applications. Toward this direction,in this paper,we describe the development of a MS2-based cell functional assay for testing cell migration (the Mkit). The system is constructed as an integrated test kit,which includes microfluidic chips,a smartphone-based imaging platform,the phone apps for image capturing and data analysis,and a set of reagent and accessories for performing the cell migration assay. We demonstrated that the Mkit can effectively measure purified neutrophil and cancer cell chemotaxis. Furthermore,neutrophil chemotaxis can be tested from a drop of whole blood using the Mkit with red blood cell (RBC) lysis. The effects of chemoattractant dose and gradient profile on neutrophil chemotaxis were also tested using the Mkit. In addition to research applications,we demonstrated the effective use of the Mkit for on-site test at the hospital and for testing clinical samples from chronic obstructive pulmonary disease patient. Thus,this developed Mkit provides an easy and integrated experimental platform for cell migration related research and potential medical diagnostic applications. View Publication

产品号#：

19666

产品名：

EasySep™ Direct人中性粒细胞分选试剂盒

文献

Xu MM et al. (AUG 2017) Immunity 47 2 363--373.e5

Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein α Signaling.

Inhibition of cytosolic DNA sensing represents a strategy that tumor cells use for immune evasion,but the underlying mechanisms are unclear. Here we have shown that CD47-signal regulatory protein α (SIRPα) axis dictates the fate of ingested DNA in DCs for immune evasion. Although macrophages were more potent in uptaking tumor DNA,increase of DNA sensing by blocking the interaction of SIRPα with CD47 preferentially occurred in dendritic cells (DCs) but not in macrophages. Mechanistically,CD47 blockade enabled the activation of NADPH oxidase NOX2 in DCs,which in turn inhibited phagosomal acidification and reduced the degradation of tumor mitochondrial DNA (mtDNA) in DCs. mtDNA was recognized by cyclic-GMP-AMP synthase (cGAS) in the DC cytosol,contributing to type I interferon (IFN) production and antitumor adaptive immunity. Thus,our findings have demonstrated how tumor cells inhibit innate sensing in DCs and suggested that the CD47-SIRPα axis is critical for DC-driven antitumor immunity. View Publication

产品号#：

18780

18780RF

18781

18781RF

19853

19853RF

70025

70025.1

70025.2

70025.3

产品名：

EasySep™ 小鼠CD11c正选试剂盒 II

RoboSep™ 小鼠CD11c正选试剂盒II

EasySep™小鼠CD11c正选试剂盒II及脾脏解离液

RoboSep™ 小鼠CD11c正选试剂盒II及脾脏解离液

EasySep™小鼠CD8+ T细胞分选试剂盒

RoboSep™ 小鼠CD8+ T细胞分选试剂盒

冻存的人外周血单个核细胞

文献

Xing J et al. (OCT 2017) Translational oncology 10 5 780--785

BiHC, a T-Cell-Engaging Bispecific Recombinant Antibody, Has Potent Cytotoxic Activity Against Her2 Tumor Cells.

Among different cancer immunotherapy approaches,bispecific antibodies (BsAbs) are of great interest due to their ability to recruit immune cells to kill tumor cells directly. Various BsAbs against Her2 tumor cells have been proposed with potent cytotoxic activities. However,most of these formats require extensive processing to obtain heterodimeric bispecific antibodies. In this study,we describe a bispecific antibody,BiHC (bispecific Her2-CD3 antibody),constructed with a single-domain anti-Her2 and a single-chain Fv (variable fragment) of anti-CD3 in an IgG-like format. In contrast to most IgG-like BsAbs,the two arms in BiHC have different molecular weights,making it easier to separate hetero- or homodimers. BiHC can be expressed in Escherichia coli and purified via Protein A affinity chromatography. The purified BiHC can recruit T cells and induce specific cytotoxicity of Her2-expressing tumor cells in vitro. The BiHC can also efficiently inhibit the tumor growth in vivo. Thus,BiHC is a promising candidate for the treatment of Her2-positive cancers. View Publication

产品号#：

17851

17851RF

产品名：

EasySep™人CD3正选试剂盒II

RoboSep™ 人CD3正选试剂盒II

文献

Wu X et al. (JAN 2018) Cell 172 3 423--438.e25

Intrinsic Immunity Shapes Viral Resistance of Stem Cells.

Stem cells are highly resistant to viral infection compared to their differentiated progeny; however,the mechanism is mysterious. Here,we analyzed gene expression in mammalian stem cells and cells at various stages of differentiation. We find that,conserved across species,stem cells express a subset of genes previously classified as interferon (IFN) stimulated genes (ISGs) but that expression is intrinsic,as stem cells are refractory to interferon. This intrinsic ISG expression varies in a cell-type-specific manner,and many ISGs decrease upon differentiation,at which time cells become IFN responsive,allowing induction of a broad spectrum of ISGs by IFN signaling. Importantly,we show that intrinsically expressed ISGs protect stem cells against viral infection. We demonstrate the in vivo importance of intrinsic ISG expression for protecting stem cells and their differentiation potential during viral infection. These findings have intriguing implications for understanding stem cell biology and the evolution of pathogen resistance. View Publication

产品号#：

02691

04434

04444

05110

05711

72052

72054

72302

72304

72307

72308

60062BT

60062FI

60062FI.1

60062PE

60062PE.1

60045

60045AZ

60045AZ.1

60045BT

60045FI

60045FI.1

产品名：

StemSpan™CD34+扩增补充（10X）

MethoCult™H4434经典

STEMdiff™权威内胚层检测试剂盒

NeuroCult™ SM1 神经添加物

CHIR99021

Y-27632（二盐酸盐）

Anti-Human SSEA-4 Antibody, Clone MC-813-70，Biotin

Anti-Human SSEA-4 Antibody, Clone MC-813-70，FITC

Anti-Human SSEA-4 Antibody, Clone MC-813-70，PE

抗人CD90抗体, 克隆号5E10

抗人CD90抗体，克隆5E10，APC

抗人CD90抗体，克隆5E10，Biotin

抗人CD90抗体，克隆5E10，FITC

文献

Wang X et al. ( 2012) Journal of immunotherapy (Hagerstown,Md. : 1997) 35 9 689--701

Phenotypic and functional attributes of lentivirus-modified CD19-specific human CD8+ central memory T cells manufactured at clinical scale.

A key determinant of the therapeutic potency of adoptive T-cell transfer is the extent to which infused cells can persist and expand in vivo. Ex vivo propagated virus-specific and chimeric antigen receptor (CAR)-redirected antitumor CD8 effector T cells derived from CD45RA(-) CD62L(+) central memory (TCM) precursors engraft long-term and reconstitute functional memory after adoptive transfer. Here,we describe a clinical scale,closed system,immunomagnetic selection method to isolate CD8(+) T(CM) from peripheral blood mononuclear cells (PBMC). This method uses the CliniMACS device to first deplete CD14(+),CD45RA(+),and CD4(+) cells from PBMC,and then to positively select CD62L(+) cells. The average purity and yield of CD8(+) CD45RA(-) CD62L TCM obtained in full-scale qualification runs were 70% and 0.4% (of input PBMC),respectively. These CD8(+) T(CM) are responsive to anti-CD3/CD28 bead stimulation,and can be efficiently transduced with CAR encoding lentiviral vectors,and undergo sustained expansion in interleukin (IL)-2/IL-15 over 3-6 weeks. The resulting CD8(+) T(CM)-derived effectors are polyclonal,retain expression of CD62L and CD28,exhibit CAR-redirected antitumor effector function,and are capable of huIL-15-dependent in vivo homeostatic engraftment after transfer to immunodeficient NOD/Scid IL-2RgCnull mice. Adoptive therapy using purified T(CM) cells is now the subject of a Food and Drug Administration-authorized clinical trial for the treatment of CD19(+) B-cell malignancies,and 3 clinical cell products expressing a CD19-specific CAR for IND 14645 have already been successfully generated from lymphoma patients using this manufacturing platform. View Publication

产品号#：

07933

07953

07949

产品名：

CryoStor®CS5

Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation.

Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice.

CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation.

Diversification of human plasmacytoid predendritic cells in response to a single stimulus.

Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity.

Mkit: A cell migration assay based on microfluidic device and smartphone.

Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein α Signaling.

BiHC, a T-Cell-Engaging Bispecific Recombinant Antibody, Has Potent Cytotoxic Activity Against Her2 Tumor Cells.

Intrinsic Immunity Shapes Viral Resistance of Stem Cells.

Phenotypic and functional attributes of lentivirus-modified CD19-specific human CD8+ central memory T cells manufactured at clinical scale.

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