产品说明

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

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

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

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

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

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

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

05712

05872

05873

18056

18056RF

72052

72054

72302

72304

72307

72308

70039

70039.1

70039.2

70039.3

70039.4

70039.5

70039.6

60062

60062BT

60062FI

60062FI.1

60062PE

60062PE.1

60045

60045AZ

60045AZ.1

60045BT

60045FI

60045FI.1

600

产品名：

StemSpan™CD34+扩增补充（10X）

MethoCult™H4434经典

STEMdiff™定型内胚层检测试剂盒

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

抗人SSEA-4抗体, 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

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

Tan Q et al. (JAN 2018) JCI insight 3 1

Activation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice.

B cells play an important role in type 1 diabetes (T1D) development. However,the role of B cell activation-induced cytidine deaminase (AID) in diabetes development is not clear. We hypothesized that AID is important in the immunopathogenesis of T1D. To test this hypothesis,we generated AID-deficient (AID-/-) NOD mice. We found that AID-/-NOD mice developed accelerated T1D,with worse insulitis and high levels of anti-insulin autoantibody in the circulation. Interestingly,neither maternal IgG transferred through placenta,nor IgA transferred through milk affected the accelerated diabetes development. AID-/-NOD mice showed increased activation and proliferation of B and T cells. We found enhanced T-B cell interactions in AID-/-NOD mice,with increased T-bet and IFN-γ expression in CD4+ T cells in the presence of AID-/- B cells. Moreover,excessive lymphoid expansion was observed in AID-/-NOD mice. Importantly,antigen-specific BDC2.5 CD4+ T cells caused more rapid onset of diabetes when cotransferred with AID-/- B cells than when cotransferred with AID+/+ B cells. Thus,our study provides insights into the role of AID in T1D. Our data also suggest that AID is a negative regulator of immune tolerance and ablation of AID can lead to exacerbated islet autoimmunity and accelerated T1D development. View Publication

产品号#：

19854

19854RF

产品名：

EasySep™小鼠B细胞分选试剂盒

RoboSep™ 小鼠B细胞分选试剂盒

Stutz MD et al. (DEC 2017) Cell death and differentiation

Necroptotic signaling is primed in Mycobacterium tuberculosis-infected macrophages, but its pathophysiological consequence in disease is restricted.

Mixed lineage kinase domain-like (MLKL)-dependent necroptosis is thought to be implicated in the death of mycobacteria-infected macrophages,reportedly allowing escape and dissemination of the microorganism. Given the consequent interest in developing inhibitors of necroptosis to treat Mycobacterium tuberculosis (Mtb) infection,we used human pharmacologic and murine genetic models to definitively establish the pathophysiological role of necroptosis in Mtb infection. We observed that Mtb infection of macrophages remodeled the intracellular signaling landscape by upregulating MLKL,TNFR1,and ZBP1,whilst downregulating cIAP1,thereby establishing a strong pro-necroptotic milieu. However,blocking necroptosis either by deleting Mlkl or inhibiting RIPK1 had no effect on the survival of infected human or murine macrophages. Consistent with this,MLKL-deficiency or treatment of humanized mice with the RIPK1 inhibitor Nec-1s did not impact on disease outcomes in vivo,with mice displaying lung histopathology and bacterial burdens indistinguishable from controls. Therefore,although the necroptotic pathway is primed by Mtb infection,macrophage necroptosis is ultimately restricted to mitigate disease pathogenesis. We identified cFLIP upregulation that may promote caspase 8-mediated degradation of CYLD,and other necrosome components,as a possible mechanism abrogating Mtb's capacity to coopt necroptotic signaling. Variability in the capacity of these mechanisms to interfere with necroptosis may influence disease severity and could explain the heterogeneity of Mtb infection and disease. View Publication

产品号#：

70008

70008.1

70008.2

70008.3

70008.4

70008.5

70008.6

200-0000

200-0001

200-0002

产品名：

冻存的人脐带血CD34+细胞

C. R. Seehus et al. (DEC 2017) Nature communications 8 1 1900

Alternative activation generates IL-10 producing type 2 innate lymphoid cells.

Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor expression with CD4+ Th2 cells,but functional diversity of the ILC2 lineage has yet to be fully explored. Here,we show induction of a molecularly distinct subset of activated lung ILC2,termed ILC210. These cells produce IL-10 and downregulate some pro-inflammatory genes. Signals that generate ILC210 are distinct from those that induce IL-13 production,and gene expression data indicate that an alternative activation pathway leads to the generation of ILC210. In vivo,IL-2 enhances ILC210 generation and is associated with decreased eosinophil recruitment to the lung. Unlike most activated ILC2,the ILC210 population contracts after cessation of stimulation in vivo,with maintenance of a subset that can be recalled by restimulation,analogous to T-cell effector cell and memory cell generation. These data demonstrate the generation of a previously unappreciated IL-10 producing ILC2 effector cell population. View Publication

产品号#：

19860

19860RF

85415

85420

85450

85460

86415

86420

86450

86460

产品名：

EasySep™ 小鼠Streptavidin RapidSpheres™分选试剂盒

RoboSep™ 小鼠Streptavidin RapidSpheres™分选试剂盒

SepMate™-15 (IVD), 100 units

SepMate™-15 (IVD)

SepMate™-50 (IVD)

SepMate™-15 (RUO), 100 units

SepMate™-15 (RUO)

SepMate™-50 (RUO)

Scalzo-Inguanti K et al. (MAY 2017) Journal of leukocyte biology

A neutralizing anti-G-CSFR antibody blocks G-CSF-induced neutrophilia without inducing neutropenia in nonhuman primates.

Neutrophils are the most abundant WBCs and have an essential role in the clearance of pathogens. Tight regulation of neutrophil numbers and their recruitment to sites of inflammation is critical in maintaining a balanced immune response. In various inflammatory conditions,such as rheumatoid arthritis,vasculitis,cystic fibrosis,and inflammatory bowel disease,increased serum G-CSF correlates with neutrophilia and enhanced neutrophil infiltration into inflamed tissues. We describe a fully human therapeutic anti-G-CSFR antibody (CSL324) that is safe and well tolerated when administered via i.v. infusion to cynomolgus macaques. CSL324 was effective in controlling G-CSF-mediated neutrophilia when administered either before or after G-CSF. A single ascending-dose study showed CSL324 did not alter steady-state neutrophil numbers,even at doses sufficient to completely prevent G-CSF-mediated neutrophilia. Weekly infusions of CSL324 (%10 mg/kg) for 3 wk completely neutralized G-CSF-mediated pSTAT3 phosphorylation without neutropenia. Moreover,repeat dosing up to 100 mg/kg for 12 wk did not result in neutropenia at any point,including the 12-wk follow-up after the last infusion. In addition,CSL324 had no observable effect on basic neutrophil functions,such as phagocytosis and oxidative burst. These data suggest that targeting G-CSFR may provide a safe and effective means of controlling G-CSF-mediated neutrophilia as observed in various inflammatory diseases. View Publication

产品号#：

70008

70008.1

70008.2

70008.3

70008.4

70008.5

70008.6

200-0000

200-0001

200-0002

70002

70002.1

70002.2

70002.3

70002.4

70002.5

产品名：

冻存的人脐带血CD34+细胞

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.

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.

Activation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice.

Necroptotic signaling is primed in Mycobacterium tuberculosis-infected macrophages, but its pathophysiological consequence in disease is restricted.

Alternative activation generates IL-10 producing type 2 innate lymphoid cells.

A neutralizing anti-G-CSFR antibody blocks G-CSF-induced neutrophilia without inducing neutropenia in nonhuman primates.

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