The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus.
Mutations at the steel locus (Sl) of the mouse affect the same cellular targets as mutations at the white spotting locus (W),which is allelic with the c-kit proto-oncogene. We show that KL,a hematopoietic growth factor obtained from conditioned medium of BALB/c 3T3 fibroblasts that stimulates the proliferation of mast cells and early erythroid progenitors,specifically binds to the c-kit receptor. The predicted amino acid sequence of isolated KL-specific cDNA clones suggests that KL is synthesized as an integral transmembrane protein. Linkage analysis maps the KL gene to the Sl locus on mouse chromosome 10,and KL sequences are deleted in the genome of the Sl mouse. These results indicate that the Sl locus encodes the ligand of the c-kit receptor,KL.
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产品类型:
产品号#:
02731
02931
产品名:
Feng Y et al. (SEP 2010)
Progress in biophysics and molecular biology 103 1 148--56
Unique biomechanical interactions between myeloma cells and bone marrow stroma cells.
We observed that BMSCs (bone marrow stromal cells) from myeloma patients (myeloma BMSCs) were significantly stiffer than control BMSCs using a cytocompression device. The stiffness of myeloma BMSCs and control BMSCs was further increased upon priming by myeloma cells. Additionally,myeloma cells became stiffer when primed by myeloma BMSCs. The focal adhesion kinase activity of myeloma cells was increased when cells were on stiffer collagen gels and on myeloma BMSCs. This change in myeloma stiffness is associated with increased colony formation of myeloma cells and FAK activation when co-cultured with stiffer myeloma BMSCs or stiffer collagen. Additionally,stem cells of RPMI8226 cells became stiffer after priming by myeloma BMSCs,with concomitant increases of stem cell colony formation. These results suggest the presence of a mechanotransduction loop between myeloma cells and myeloma BMSCs to increase the stiffness of both types of cells via FAK activation. The increase of stiffness may in turn support the growth of myeloma cells and myeloma stem cells.
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Mesenchymal stem cells can be differentiated into endothelial cells in vitro.
Human bone marrow-derived mesenchymal stem cells (MSCs) have the potential to differentiate into mesenchymal tissues like osteocytes,chondrocytes,and adipocytes in vivo and in vitro. The aim of this study was to investigate the in vitro differentiation of MSCs into cells of the endothelial lineage. MSCs were generated out of mononuclear bone marrow cells from healthy donors separated by density gradient centrifugation. Cells were characterized by flow cytometry using a panel of monoclonal antibodies and were tested for their potential to differentiate along different mesenchymal lineages. Isolated MSCs were positive for the markers CD105,CD73,CD166,CD90,and CD44 and negative for typical hematopoietic and endothelial markers. They were able to differentiate into adipocytes and osteocytes after cultivation in respective media. Differentiation into endothelial-like cells was induced by cultivation of confluent cells in the presence of 2% fetal calf serum and 50 ng/ml vascular endothelial growth factor. Laser scanning cytometry analysis of the confluent cells in situ showed a strong increase of expression of endothelial-specific markers like KDR and FLT-1,and immunofluorescence analysis showed typical expression of the von Willebrand factor. The functional behavior of the differentiated cells was tested with an in vitro angiogenesis test kit where cells formed characteristic capillary-like structures. We could show the differentiation of expanded adult human MSCs into cells with phenotypic and functional features of endothelial cells. These predifferentiated cells provide new options for engineering of artificial tissues based on autologous MSCs and vascularized engineered tissues.
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产品类型:
产品号#:
05401
产品名:
MesenCult™ MSC基础培养基 (人)
McPherson CA et al. (JUL 2011)
Brain,behavior,and immunity 25 5 850--62
Interleukin (IL)-1 and IL-6 regulation of neural progenitor cell proliferation with hippocampal injury: differential regulatory pathways in the subgranular zone (SGZ) of the adolescent and mature mouse brain.
Current data suggests an association between elevations in interleukin 1 (IL-1)α,IL-1β,and IL-6 and the proliferation of neural progenitor cells (NPCs) following brain injury. A limited amount of work implicates changes in these pro-inflammatory responses with diminished NPC proliferation observed as a function of aging. In the current study,adolescent (21day-old) and 1year-old CD-1 male mice were injected with trimethyltin (TMT,2.3mg/kg,i.p.) to produce acute apoptosis of hippocampal dentate granule cells. In this model,fewer 5-bromo-2'-deoxyuridine (BrdU)+ NPC were observed in both naive and injured adult hippocampus as compared to the corresponding number seen in adolescent mice. At 48h post-TMT,a similar level of neuronal death was observed across ages,yet activated ameboid microglia were observed in the adolescent and hypertrophic process-bearing microglia in the adult. IL-1α mRNA levels were elevated in the adolescent hippocampus; IL-6 mRNA levels were elevated in the adult. In subgranular zone (SGZ) isolated by laser-capture microdissection,IL-1β was detected but not elevated by TMT,IL-1a was elevated at both ages,while IL-6 was elevated only in the adult. Naïve NPCs isolated from the hippocampus expressed transcripts for IL-1R1,IL-6Rα,and gp130 with significantly higher levels of IL-6Rα mRNA in the adult. In vitro,IL-1α (150pg/ml) stimulated proliferation of adolescent NPCs; IL-6 (10ng/ml) inhibited proliferation of adolescent and adult NPCs. Microarray analysis of SGZ post-TMT indicated a prominence of IL-1a/IL-1R1 signaling in the adolescent and IL-6/gp130 signaling in the adult.
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产品类型:
产品号#:
05700
05701
05702
05707
05715
05740
产品名:
NeuroCult™ 基础培养基(小鼠&大鼠)
NeuroCult™ 扩增添加物 (小鼠&大鼠)
NeuroCult™ 扩增试剂盒 (小鼠&大鼠)
NeuroCult™化学解离试剂盒(小鼠)
NeuroCult™成年中枢神经系统(CNS)组织酶解试剂盒(小鼠和大鼠)
Sugimura R et al. (MAY 2017)
Nature 545 7655 432--438
Haematopoietic stem and progenitor cells from human pluripotent stem cells.
A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens,or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here,to yield functional human haematopoietic stem cells,we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG,HOXA5,HOXA9,HOXA10,LCOR,RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid,B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders.
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Akutsu H et al. (JAN 2006)
Methods in enzymology 418 78--92
Human embryonic stem cells.
Human embryonic stem cells hold great promise in furthering our treatment of disease and increasing our understanding of early development. This chapter describes protocols for the derivation and maintenance of human embryonic stem cells. In addition,it summarizes briefly several alternative methods for the culture of human embryonic stem cells. Thus,this chapter provides a good starting point for researchers interested in harnessing the potential of human embryonic stem cells.
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产品类型:
产品号#:
05850
05857
05870
05875
85850
85857
85870
85875
产品名:
mTeSR™1
mTeSR™1
P. B. Olkhanud et al. (MAY 2011)
Cancer research 71 10 3505--15
Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4⁺ T cells to T-regulatory cells.
Pulmonary metastasis of breast cancer requires recruitment and expansion of T-regulatory cells (Treg) that promote escape from host protective immune cells. However,it remains unclear precisely how tumors recruit Tregs to support metastatic growth. Here we report the mechanistic involvement of a unique and previously undescribed subset of regulatory B cells. These cells,designated tumor-evoked Bregs (tBreg),phenotypically resemble activated but poorly proliferative mature B2 cells (CD19(+) CD25(High) CD69(High)) that express constitutively active Stat3 and B7-H1(High) CD81(High) CD86(High) CD62L(Low) IgM(Int). Our studies with the mouse 4T1 model of breast cancer indicate that the primary role of tBregs in lung metastases is to induce TGF-$\beta$-dependent conversion of FoxP3(+) Tregs from resting CD4(+) T cells. In the absence of tBregs,4T1 tumors cannot metastasize into the lungs efficiently due to poor Treg conversion. Our findings have important clinical implications,as they suggest that tBregs must be controlled to interrupt the initiation of a key cancer-induced immunosuppressive event that is critical to support cancer metastasis.
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产品类型:
产品号#:
产品名:
Yamashita J et al. (NOV 2000)
Nature 408 6808 92--6
Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors.
Interaction between endothelial cells and mural cells (pericytes and vascular smooth muscle) is essential for vascular development and maintenance. Endothelial cells arise from Flk1-expressing (Flk1+) mesoderm cells,whereas mural cells are believed to derive from mesoderm,neural crest or epicardial cells and migrate to form the vessel wall. Difficulty in preparing pure populations of these lineages has hampered dissection of the mechanisms underlying vascular formation. Here we show that Flk1+ cells derived from embryonic stem cells can differentiate into both endothelial and mural cells and can reproduce the vascular organization process. Vascular endothelial growth factor promotes endothelial cell differentiation,whereas mural cells are induced by platelet-derived growth factor-BB. Vascular cells derived from Flk1+ cells can organize into vessel-like structures consisting of endothelial tubes supported by mural cells in three-dimensional culture. Injection of Flk1+ cells into chick embryos showed that they can incorporate as endothelial and mural cells and contribute to the developing vasculature in vivo. Our findings indicate that Flk1+ cells can act as 'vascular progenitor cells' to form mature vessels and thus offer potential for tissue engineering of the vascular system.
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产品类型:
产品号#:
06902
06952
00321
00322
00323
00324
00325
产品名:
D'Amour KA et al. (NOV 2006)
Nature biotechnology 24 11 1392--401
Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells.
Of paramount importance for the development of cell therapies to treat diabetes is the production of sufficient numbers of pancreatic endocrine cells that function similarly to primary islets. We have developed a differentiation process that converts human embryonic stem (hES) cells to endocrine cells capable of synthesizing the pancreatic hormones insulin,glucagon,somatostatin,pancreatic polypeptide and ghrelin. This process mimics in vivo pancreatic organogenesis by directing cells through stages resembling definitive endoderm,gut-tube endoderm,pancreatic endoderm and endocrine precursor--en route to cells that express endocrine hormones. The hES cell-derived insulin-expressing cells have an insulin content approaching that of adult islets. Similar to fetal beta-cells,they release C-peptide in response to multiple secretory stimuli,but only minimally to glucose. Production of these hES cell-derived endocrine cells may represent a critical step in the development of a renewable source of cells for diabetes cell therapy.
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产品类型:
产品号#:
72072
72074
72082
72262
72264
100-1045
产品名:
环巴胺(Cyclopamine)
环巴胺(Cyclopamine)
DAPT
All-Trans Retinoic Acid
全反式视黄酸
全反式视黄酸
Cai J et al. (MAY 2007)
Hepatology (Baltimore,Md.) 45 5 1229--39
Directed differentiation of human embryonic stem cells into functional hepatic cells.
UNLABELLED The differentiation capacity of human embryonic stem cells (hESCs) holds great promise for therapeutic applications. We report a novel three-stage method to efficiently direct the differentiation of human embryonic stem cells into hepatic cells in serum-free medium. Human ESCs were first differentiated into definitive endoderm cells by 3 days of Activin A treatment. Next,the presence of fibroblast growth factor-4 and bone morphogenetic protein-2 in the culture medium for 5 days induced efficient hepatic differentiation from definitive endoderm cells. Approximately 70% of the cells expressed the hepatic marker albumin. After 10 days of further in vitro maturation,these cells expressed the adult liver cell markers tyrosine aminotransferase,tryptophan oxygenase 2,phosphoenolpyruvate carboxykinase (PEPCK),Cyp7A1,Cyp3A4 and Cyp2B6. Furthermore,these cells exhibited functions associated with mature hepatocytes including albumin secretion,glycogen storage,indocyanine green,and low-density lipoprotein uptake,and inducible cytochrome P450 activity. When transplanted into CCl4 injured severe combined immunodeficiency mice,these cells integrated into the mouse liver and expressed human alpha-1 antitrypsin for at least 2 months. In addition,we found that the hESC-derived hepatic cells were readily infected by human immunodeficiency virus-hepatitis C virus pseudotype viruses. CONCLUSION We have developed an efficient way to direct the differentiation of human embryonic stem cells into cells that exhibit characteristics of mature hepatocytes. Our studies should facilitate searching the molecular mechanisms underlying human liver development,and form the basis for hepatocyte transplantation and drug tests.
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